Nano Medicine

Breath analyzer

2009-06-11T21:04:00.001-07:00

Nanotechnology breath analyzer for kidney failure
(Nanowerk Spotlight)

High blood pressure and diabetes, increasingly common signs of the unhealthy lifestyle in most Western societies, often are the cause for chronic kidney disease (or chronic renal disease; CKD). CKD is a long-standing, progressive deterioration of renal function. In its end-stage, the disease is a debilitating medical condition of chronic kidney failure which requires intensive and costly treatments through dialysis or even transplantation. Initially, as renal tissue loses function, there are few abnormalities because the remaining tissue increases its performance. Diagnosis of CKD is mostly based on laboratory testing of renal function such as plasma levels of creatinine and urea, sometimes followed by renal biopsy. Imaging techniques are also applied to detect changes in size, texture, and position of the kidneys. These measurements are performed using ultrasound and are suitable only in patients suffering from progressive renal failure. Presently, renal biopsy remains the most definitive test to specifically diagnose chronic and acute renal failure. This method is invasive and thus comprises the risk of infections and bleeding among other possible complications. "So far, blood tests and urinalysis are the golden standard to identify a decline in kidney filtration, wherein high levels of creatinine and blood urea nitrogen usually reflect renal dysfunction – however, these tests tend to be highly inaccurate and may remain within the normal range even while 65-75% of kidney function is lost." Hossam Haick, senior lecturer in the Faculty of Chemical Engineering and the Russell Berrie Nanotechnology Institute at Technion-Israel Institute of Technology, tells Nanowerk. "Given the difficulties in separating healthy renal function from dysfunction, it is perhaps not too surprising that precise biochemical or clinical criteria for diagnosis of acute renal failure have been elusive. Therefore, there is an unmet need for a noninvasive method for detection of renal failure of various etiologies. Furthermore, the challenge remains to diagnose renal disorders with sufficient sensitivity and specificity to provide a large-scale screening technique, feasible for clinical practice, for people at increased risk of developing renal dysfunction." Haick, Zaid Abassi and coworkers from Technion used an experimental model of end stage renal disease (ESRD) in rats to identify by advanced, yet simple nanotechnology-based approach to discriminate between exhaled breath of healthy states and of ESRD states. The team reported their findings in the April 27, 2009 online edition of ACS Nano ("Sniffing Chronic Renal Failure in Rat Model by an Array of Random Networks of Single-Walled Carbon Nanotubes"). In their work, Haick and his team used gas chromatography/ mass spectroscopy in conjugation with solid phase microextraction of healthy and ESRD breath, collected directly from the trachea of the rats, to identify 15 common volatile organic compounds (VOCs) in all samples of healthy and ESRD states and 27 VOCs that appear in diseased rats but not in healthy states.
Online breath analysis via an array of chemiresistive random network of single walled carbon nanotubes (SWCNTs) coated with organic materials showed excellent discrimination between the various breath states. Furthermore, the analysis shows the adequacy of using representative simulated VOCs to imitate the breath of healthy and ESRD states and, therefore, to train the sensors’ array the pertinent breath signatures. "Using SWCNT networks circumvents the requirement of position and structural control (as is the case in devices based on individual SWCNT) because the devices display the averaged usual properties of many randomly distributed SWCNTs," says Haick. "An additional feature of SWCNT networks is that they can be processed into devices of arbitrary size using conventional microfabrication technology." An important implication of these findings, besides the detection of diseases directly related to the respiratory, cardiovascular, and renal systems, is the fact that VOCs are mainly blood borne and the concentration of biologically relevant substances in exhaled breath closely reflects that in the arterial system. Therefore, breath is predestined for monitoring different processes in the body.
Apart from the odor impression of chronic kidney failure, much about the biochemical processes and the formation of marker substances is already known. Haick notes that analysis of the various breath samples by an array of chemiresistive random network of SWCNTs showed excellent discrimination between the various breath states, while revealing significantly enhanced discriminations at lower humidity levels in the breath. "Furthermore, we show that it is enough to use selected number of simulated VOCs to 'train' the sensors’ array system to discriminate between the electronic patterns of healthy states and chronic failure states," says Haick. "Experiments to distinguish less severe kidney failure (e.g., 35-70% reduction in kidney function) and to distinguish chronic kidney failure from other disease (or patho-physiological) states that have a potential to produce a distorted profile of breath VOCs (e.g., liver failure, systemic infection, pneumonia, heart failure, etc.) are underway and will be published soon." The excellent discrimination between the various breath states obtained in this study provides expectations for future capabilities for diagnosis, detection, and screening various stages of kidney disease, especially in the early stages of the disease, where it is possible to control blood pressure, fat, glucose and protein intake to slow the progression. In terms of the devices, the challenges could be summarized in how to bring the sensing technology to a level that it will be very simple to use, lightweight, low-power, and able to detect diseases in noninvasive way (i.e., via breath samples) in real time.
By Michael Berger.
Nanowerk LLC

Breath analyzer

2009-06-11T21:04:00.000-07:00

Nanotechnology breath analyzer for kidney failure

(Nanowerk Spotlight)

High blood pressure and diabetes, increasingly common signs of the unhealthy lifestyle in most Western societies, often are the cause for chronic kidney disease (or chronic renal disease; CKD). CKD is a long-standing, progressive deterioration of renal function. In its end-stage, the disease is a debilitating medical condition of chronic kidney failure which requires intensive and costly treatments through dialysis or even transplantation. Initially, as renal tissue loses function, there are few abnormalities because the remaining tissue increases its performance. Diagnosis of CKD is mostly based on laboratory testing of renal function such as plasma levels of creatinine and urea, sometimes followed by renal biopsy. Imaging techniques are also applied to detect changes in size, texture, and position of the kidneys. These measurements are performed using ultrasound and are suitable only in patients suffering from progressive renal failure. Presently, renal biopsy remains the most definitive test to specifically diagnose chronic and acute renal failure. This method is invasive and thus comprises the risk of infections and bleeding among other possible complications. "So far, blood tests and urinalysis are the golden standard to identify a decline in kidney filtration, wherein high levels of creatinine and blood urea nitrogen usually reflect renal dysfunction – however, these tests tend to be highly inaccurate and may remain within the normal range even while 65-75% of kidney function is lost." Hossam Haick, senior lecturer in the Faculty of Chemical Engineering and the Russell Berrie Nanotechnology Institute at Technion-Israel Institute of Technology, tells Nanowerk. "Given the difficulties in separating healthy renal function from dysfunction, it is perhaps not too surprising that precise biochemical or clinical criteria for diagnosis of acute renal failure have been elusive. Therefore, there is an unmet need for a noninvasive method for detection of renal failure of various etiologies. Furthermore, the challenge remains to diagnose renal disorders with sufficient sensitivity and specificity to provide a large-scale screening technique, feasible for clinical practice, for people at increased risk of developing renal dysfunction." Haick, Zaid Abassi and coworkers from Technion used an experimental model of end stage renal disease (ESRD) in rats to identify by advanced, yet simple nanotechnology-based approach to discriminate between exhaled breath of healthy states and of ESRD states. The team reported their findings in the April 27, 2009 online edition of ACS Nano ("Sniffing Chronic Renal Failure in Rat Model by an Array of Random Networks of Single-Walled Carbon Nanotubes"). In their work, Haick and his team used gas chromatography/ mass spectroscopy in conjugation with solid phase microextraction of healthy and ESRD breath, collected directly from the trachea of the rats, to identify 15 common volatile organic compounds (VOCs) in all samples of healthy and ESRD states and 27 VOCs that appear in diseased rats but not in healthy states.
Online breath analysis via an array of chemiresistive random network of single walled carbon nanotubes (SWCNTs) coated with organic materials showed excellent discrimination between the various breath states. Furthermore, the analysis shows the adequacy of using representative simulated VOCs to imitate the breath of healthy and ESRD states and, therefore, to train the sensors’ array the pertinent breath signatures. "Using SWCNT networks circumvents the requirement of position and structural control (as is the case in devices based on individual SWCNT) because the devices display the averaged usual properties of many randomly distributed SWCNTs," says Haick. "An additional feature of SWCNT networks is that they can be processed into devices of arbitrary size using conventional microfabrication technology." An important implication of these findings, besides the detection of diseases directly related to the respiratory, cardiovascular, and renal systems, is the fact that VOCs are mainly blood borne and the concentration of biologically relevant substances in exhaled breath closely reflects that in the arterial system. Therefore, breath is predestined for monitoring different processes in the body.
Apart from the odor impression of chronic kidney failure, much about the biochemical processes and the formation of marker substances is already known. Haick notes that analysis of the various breath samples by an array of chemiresistive random network of SWCNTs showed excellent discrimination between the various breath states, while revealing significantly enhanced discriminations at lower humidity levels in the breath. "Furthermore, we show that it is enough to use selected number of simulated VOCs to 'train' the sensors’ array system to discriminate between the electronic patterns of healthy states and chronic failure states," says Haick. "Experiments to distinguish less severe kidney failure (e.g., 35-70% reduction in kidney function) and to distinguish chronic kidney failure from other disease (or patho-physiological) states that have a potential to produce a distorted profile of breath VOCs (e.g., liver failure, systemic infection, pneumonia, heart failure, etc.) are underway and will be published soon." The excellent discrimination between the various breath states obtained in this study provides expectations for future capabilities for diagnosis, detection, and screening various stages of kidney disease, especially in the early stages of the disease, where it is possible to control blood pressure, fat, glucose and protein intake to slow the progression. In terms of the devices, the challenges could be summarized in how to bring the sensing technology to a level that it will be very simple to use, lightweight, low-power, and able to detect diseases in noninvasive way (i.e., via breath samples) in real time.

By Michael Berger.

Nanowerk LLC

Biosensing

2009-06-11T21:02:00.000-07:00

Nanoparticle Libraries for Biosensing Over the past couple of years, researchers have developed a number of standardized techniques for attaching an antibody or protein to the surface of a nanoparticle in order to create a targeted drug delivery vehicle or imaging agent. This approach works well when trying to target a known cancer biomarker, but the fact is that today, researchers have only a few such markers to choose from, and many types of cancers do not express those few known markers.
In an attempt to overcome this limitation, a team of researchers at the Massachusetts General Hospital has taken a different approach, creating a large library of nanoparticles, each with a different small molecule decorating its surface. They then screen this library to see if any of the nanoparticles will bind to any number of cancer cells while ignoring healthy cells.
Reporting its work in the journal Bioconjugate Chemistry, a team led by Ralph Weissleder, M.D., and Lee Josephson, Ph.D., describes the methods they use for attaching a variety of small organic molecules to the surface of a magnetic and fluorescent nanoparticle. The researchers chose to use small molecules of “nonbiological origin” with an eye on keeping costs and regulatory burdens low should any of these nanoparticles prove clinically useful.
The researchers also worked out a method to ensure that each chemical preparation went as planned. This latter step is critically important in order to distinguish between modified nanoparticles that have no biological activity and those that have no activity because the expected chemical modifications never occurred in the first place. Finally, in order to automate the screening process, the researchers also developed two techniques for “printing” the resulting libraries of modified nanoparticles onto glass slides or for adding each member of the library to the tiny indentations on a standard 96-well assay plate used in a wide variety of screening technologies.
In a demonstration experiment, the investigators prepared a 96-well plate in which each well contained macrophages, a type of immune system cell that has a propensity to engulf nanoparticles. They then added individual members of the library to each well and identified modified nanoparticles that were not taken very effectively by macrophages (see illustration). The macrophage-avoiding nanoparticles may be able to more effectively deliver drugs to tumors since more of them may be able to reach their target rather than be eliminated from the body by macrophages.
This work, which was funded by the National Cancer Institute, is detailed in a paper titled, “Development of nanoparticle libraries for biosensing.” This paper was published online in advance of print publication.
An abstract is available at the journal’s website.
Source>http://www.nanotechwire.com/news.asp?nid=2838

Nanoparticle

2009-06-11T21:00:00.000-07:00

Combining Two Drugs in One Nanoparticle Overcomes Multidrug Resistance
Cancer cells, like bacteria, can develop resistance to drug therapy. In fact, research suggests strongly that multidrug-resistant cancer cells that remain alive after chemotherapy are responsible for the reappearance of tumors and the poor prognosis for patients whose cancer recurs. One new approach that shows promise in overcoming such multidrug resistance is to combine two different anticancer agents in one nanoscale construct, providing a one-two punch that can prove lethal to such resistant cells. This work appears in the journal Molecular Pharmaceutics.
Mansoor Amiji, Ph.D., principal investigator of the National Cancer Institute-funded Nanotherapeutic Strategy for Multidrug Resistant Tumors Platform Partnership at Northeastern University, and postdoctoral fellow Srinivas Ganta, Ph.D., created a nanoemulsion entrapping both paclitaxel and curcumin. The former compound is a widely used anticancer agent, whereas the latter comes from the spice tumeric and has been shown to inhibit several cancer-related processes.
The investigators prepared their nanoformulation by mixing the two drugs with flaxseed oil, the emulsifier lecithin from egg yolks, and the biocompatible polymer polyethylene glycol. To help track this nanoformulation, the investigators also added a fluorescent dye to the mixture. Ultrasonification for 10 minutes produced stable, nanosize droplets that were readily taken up by tumor cells grown in culture. In addition, the nanoformulation had significant anticancer activity that surpassed that of either of the two drugs administered together or separately, particularly in multidrug-resistant cells. Biochemical assays showed that the curcumin component inhibited P-glycoprotein, which tumor cells use to excrete anticancer agents and protect themselves from the effects of those agents. Both drugs also had the effect of triggering apoptosis in the treated cells.
This work, which was detailed in the paper “Coadministration of paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells,” was supported by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer.
An abstract is available at the journal’s Web site.
>http://www.nanotechwire.com/news.asp?nid=7861

Capsules Encapsulated

2009-06-11T20:58:00.000-07:00

Drug Deliver With Nanotechnology:
Capsules Encapsulated

When cells cannot carry out the tasks required of them by our bodies, the result is disease. Nanobiotechnology researchers are looking for ways to allow synthetic systems take over simple cellular activities when they are absent from the cell. This requires transport systems that can encapsulate medications and other substances and release them in a controlled fashion at the right moment.
The transporter must be able to interact with the surroundings in order to receive the signal to unload its cargo. A team led by Frank Caruso at the University of Melbourne has now developed a microcontainer that can hold thousands of individual "carrier units"—a "capsosome". These are polymer capsules in which liposomes have been embedded to form subcompartments.
Currently, the primary type of nanotransporter used for drugs is the capsule: Polymer capsules form stable containers that are semipermeable, which allows for communication with the surrounding medium. However, these are not suitable for the transport of small molecules because they can escape. Liposomes are good at protecting small drug molecules; however, they are often unstable and impermeable to substances from the environment. The Australian researchers have now combined the advantages of both systems in their capsosomes.
Capsosomes are produced by several steps. First, a layer of polymer is deposited onto small silica spheres. This polymer contains building blocks modified with cholesterol. Liposomes that have been loaded with an enzyme can be securely anchored to the cholesterol units and thus attached to the polymer film. Subsequently, more polymer layers are added and then cross-linked by disulfide bridges into a gel by means of a specially developed, very gentle cross-linking reaction. In the final step, the silica core is etched away without damaging the sensitive cargo.
Experiments with an enzyme as model cargo demonstrated that the liposomes remain intact and the cargo does not escape. Addition of a detergent releases the enzyme in a functional state. By means of the enzymatic reaction, which causes a color change of the solution, it was possible to determine the number of liposome compartments to be about 8000 per polymer capsule.
"Because the capsosomes are biodegradable and nontoxic", says Brigitte Staedler, a senior researcher in the group, "they would also be suitable for use as resorbable synthetic cell organelles and for the transport of drugs." In addition, the scientists are planning to encapsulate liposomes filled with different enzymes together and to equip them with specific "receivers" which would allow the individual cargo to be released in a targeted fashion. This would make it possible to use enzymatic reaction cascades for catalytic reaction processes.
Frank Caruso. A Microreactor with Thousands of Subcompartments: Enzyme-Loaded Liposomes within Polymer Capsules. Angewandte Chemie International Edition, 2009, 48, No. 24, 4359-4362 DOI: 10.1002/anie.200900386
>http://www.nanotechwire.com/news.asp?nid=7944

Dead or alive

2009-06-11T20:53:00.000-07:00

Nanotechnology technique tells the difference
(From Nanowerk Spotlight)

A major concern in microbiology is to determine whether a bacterium is dead or alive. This crucial question has major consequences in food industry, water supply or health care. While culture-based tests can determine whether bacteria can proliferate and form colonies, these tests are time-consuming and work poorly with certain slow-growing or non-culturable bacteria. They are not suitable for applications where real-time results are needed, e.g. in industrial manufacturing or food processing. A team of scientists in France has now discovered that living and dead cells can be discriminated with a nanotechnology technique on the basis of their cell wall nanomechanical properties. This finding is totally new and has been made possible thanks to an interdisciplinary approach which mixes physics, biology and chemistry. This work is a key stone in the understanding of bacterial cell wall behavior. "We have developed a method to probe the mechanical properties of living and dead bacteria via atomic force microscope (AFM) indentation experimentations," Aline Cerf tells Nanowerk. ". Indeed, we provide a new way to probe bacterial cell viability based on cell wall nanomechanical properties, independently from cell ability to grow on a medium or to be penetrated by a fluorescent dye." Cerf, a PhD student in the NanoBioSystems group at LAAS-CNRS, is first author of a recent paper in Langmuir ("Nanomechanical Properties of Dead or Alive Single-Patterned Bacteria") where she and collaborators from LAAS-CNRS describe their findings. "We wanted to explore the modifications that could occur in the nanomechanical properties of a single E. coli bacterium, while it is alive and while it is dead," says Etienne Dague, a researcher in the NanoBioSystems group. "To reach this goal, it has been of first importance to immobilize the living bacteria in an aqueous environment to avoid any cell wall modifications due to a drying step." Thus, in developing a technique to probe the mechanical properties of bacteria via AFM indentation experiments, the French team also came up with an immobilization method for bacteria that doesn't require a chemical fixation.
The researchers set up a fast and simple procedure – based on a conventional microcontact printing and a simple incubation technique to generate functionalized patterns so as to induce local bacteria deposition – that allowed them to produce reliable chemical patterns exhibiting different surface properties to induce selective adsorption of individual bacteria in liquid media at registered positions. "We have evidenced a selective adsorption of bacteria on these local chemical patterns, producing highly ordered arrays of single living bacteria with a success rate close to 100%," says Cerf. The team then used this controlled immobilization method to study the mechanical properties of dead or alive bacterial cell in aqueous environment. Using force spectroscopy before and after heating , they measured the Young moduli of the same cell. The cells with a damaged membrane (after heating) present a Young modulus twice as high (6.1 ? 1.5 MPa versus 3.0 ? 0.6 MPa) as that of healthy bacteria. At the same time it has been impossible to evidence a difference between the AFM images of the living and the dead cell. "We have shown that we are capable of engineering large areas with patterns of single bacteria and this will be of major interest for future applications," says Dague. "Indeed, thanks to a periodic arrangement of cells, the process consisting in measuring the nanomechanical properties of cells could possibly be automated and a tool to count live or dead bacteria could be designed."

By Michael Berger.
Nanowerk LLC >http://www.nanowerk.com/spotlight/spotid=10816.php

What is nanotechnology?(8)

2009-06-11T20:16:00.000-07:00

What is nanotechnology?
(1):> 1. The Significance of the Nanoscale
(2):>2. New Materials: Nanomaterials
(3):>2.1 Nanomaterials
(4):>3. Nanomaterial Science
(5):>3.1 Nanoscale in Two Dimensions
(6):>3.2 Nanoscale in Two Dimensions(cont.)
(7):>3.3 Nanoscale in Three Dimensions(cont.)
(8):>3.4 Nanoscale in Three Dimensions(cont.)

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3.3 Nanoscale in Three Dimensions(cont.)

b) Fullerenes (carbon 60)
Model C60In the mid-1980s a new class of carbon material was discovered called carbon 60 (C60).Harry Kroto and Richard Smalley, the experimental chemists who discovered C60 named it "buckminsterfullerene", in recognition of the architect Buckminster Fuller, who was well-known for building geodesic domes, and the term fullerenes was then given to any closed carbon cage. C60 are spherical molecules about 1nm in diameter, comprising 60 carbon atoms arranged as 20 hexagons and 12 pentagons: the configuration of a football. In 1990, a technique to produce larger quantities of C60 was developed by resistively heating graphite rods in a helium atmosphere. Several applications are envisaged for fullerenes, such as miniature ‘ball bearings’ to lubricate surfaces, drug delivery vehicles and in electronic circuits.

c) DendrimersDendrimers are spherical polymeric molecules, formed through a nanoscale hierarchical self-assembly process. There are many types of dendrimer; the smallest is several nanometres in size. Dendrimers are used in conventional applications such as coatings and inks, but they also have a range of interesting properties which could lead to useful applications. For example, dendrimers can act as nanoscale carrier molecules and as such could be used in drug delivery. Environmental clean-up could be assisted by dendrimers as they can trap metal ions, which could then be filtered out of water with ultra-filtration techniques.
d) Quantum DotsNanoparticles of semiconductors (quantum dots) were theorized in the 1970s and initially created in the early 1980s. If semiconductor particles are made small enough, quantum effects come into play, which limit the energies at which electrons and holes (the absence of an electron) can exist in the particles. As energy is related to wavelength (or colour), this means that the optical properties of the particle can be finely tuned depending on its size. Thus, particles can be made to emit or absorb specific wavelengths (colours) of light, merely by controlling their size. Recently, quantum dots have found applications in composites, solar cells (Gratzel cells) and fluorescent biological labels (for example to trace a biological molecule) which use both the small particle size and tuneable energy levels. Recent advances in chemistry have resulted in the preparation of monolayer-protected, high-quality, monodispersed, crystalline quantum dots as small as 2nm in diameter, which can be conveniently treated and processed as a typical chemical reagent.

What is nanotechnology?(7)

2009-06-11T20:13:00.000-07:00

What is nanotechnology?(6)

2009-06-11T20:10:00.000-07:00

3.2 Nanoscale in Two Dimensions(cont.)

b) Inorganic NanotubesInorganic nanotubes and inorganic fullerene-like materials based on layered compounds such as molybdenum disulphide were discovered shortly after CNTs. They have excellent tribological (lubricating) properties, resistance to shockwave impact, catalytic reactivity, and high capacity for hydrogen and lithium storage, which suggest a range of promising applications. Oxide-based nanotubes (such as titanium dioxide) are being explored for their applications in catalysis, photo-catalysis and energy storage.

c) NanowiresNanowires are ultrafine wires or linear arrays of dots, formed by self-assembly. They can be made from a wide range of materials. Semiconductor nanowires made of silicon, gallium nitride and indium phosphide have demonstrated remarkable optical, electronic and magnetic characteristics (for example, silica nanowires can bend light around very tight corners). Nanowires have potential applications in high-density data storage, either as magnetic read heads or as patterned storage media, and electronic and opto-electronic nanodevices, for metallic interconnects of quantum devices and nanodevices. The preparation of these nanowires relies on sophisticated growth techniques, which include selfassembly processes, where atoms arrange themselves naturally on stepped surfaces, chemical vapour deposition (CVD) onto patterned substrates, electroplating or molecular beam epitaxy (MBE). The ‘molecular beams’ are typically from thermally evaporated elemental sources.

d) BiopolymersThe variability and site recognition of biopolymers, such as DNA molecules, offer a wide range of opportunities for the self-organization of wire nanostructures into much more complex patterns. The DNA backbones may then, for example, be coated in metal. They also offer opportunities to link nano- and biotechnology in, for example, biocompatible sensors and small, simple motors. Such self-assembly of organic backbone nanostructures is often controlled by weak interactions, such as hydrogen bonds, hydrophobic, or van der Waals interactions (generally in aqueous environments) and hence requires quite different synthesis strategies to CNTs, for example. The combination of one-dimensional nanostructures consisting of biopolymers and inorganic compounds opens up a number of scientific and technological opportunities.

What is nanotechnology?(5)

2009-06-11T20:06:00.000-07:00

What is nanotechnology?(4)

2009-06-11T20:03:00.000-07:00

What is nanotechnology?(3)

2009-06-11T19:55:00.000-07:00

What is nanotechnology?(1):> 1. The Significance of the Nanoscale(2):>2. New Materials: Nanomaterials(3):>2.1 Nanomaterials(4):>3. Nanomaterial Science(5):>3.1 Nanoscale in Two Dimensions(6):>3.2 Nanoscale in Two Dimensions(cont.)(7):>3.3 Nanoscale in Three Dimensions(cont.)(8):>3.4 Nanoscale in Three Dimensions(cont.)

2.1 Nanomaterials

DefinitionAlthough a broad definition, we categorise nanomaterials as those which have structured components with at least one dimension less than 100nm. Materials that have one dimension in the nanoscale (and are extended in the other two dimensions) are layers, such as a thin films or surface coatings. Some of the features on computer chips come in this category. Materials that are nanoscale in two dimensions (and extended in one dimension) include nanowires and nanotubes. Materials that are nanoscale in three dimensions are particles, for example precipitates, colloids and quantum dots (tiny particles of semiconductor materials). Nanocrystalline materials, made up of nanometre-sized grains, also fall into this category. Some of these materials have been available for some time; others are genuinely new. The aim of this chapter is to give an overview of the properties, and the significant foreseeable applications of some key nanomaterials.Two principal factors cause the properties of nanomaterials to differ significantly from other materials: increased relative surface area, and quantum effects. These factors can change or enhance properties such as reactivity, strength and electrical characteristics. As a particle decreases in size, a greater proportion of atoms are found at the surface compared to those inside. For example, a particle of size 30 nm has 5% of its atoms on its surface, at 10 nm 20% of its atoms, and at 3 nm 50% of its atoms. Thus nanoparticles have a much greater surface area per unit mass compared with larger particles. As growth and catalytic chemical reactions occur at surfaces, this means that a given mass of material in nanoparticulate form will be much more reactive than the same mass of material made up of larger particles.To understand the effect of particle size on surface area, consider a U.S. silver dollar. The silver dollar contains 26.96 grams of coin silver, has a diameter of about 40 mm, and has a total surface area of approximately 27.70 square centimeters. If the same amount of coin silver were divided into tiny particles – say 1 nanometer in diameter – the total surface area of those particles would be 11,400 square meters. When the amount of coin silver contained in a silver dollar is rendered into 1 nm particles, the surface area of those particles is 4.115 million times greater than the surface area of the silver dollar!
In tandem with surface-area effects, quantum effects can begin to dominate the properties of matter as size is reduced to the nanoscale. These can affect the optical, electrical and magnetic behaviour of materials, particularly as the structure or particle size approaches the smaller end of the nanoscale. Materials that exploit these effects include quantum dots, and quantum well lasers for optoelectronics.For other materials such as crystalline solids, as the size of their structural components decreases, there is much greater interface area within the material; this can greatly affect both mechanical and electrical properties. For example, most metals are made up of small crystalline grains; the boundaries between the grain slow down or arrest the propagation of defects when the material is stressed, thus giving it strength. If these grains can be made very small, or even nanoscale in size, the interface area within the material greatly increases, which enhances its strength. For example, nanocrystalline nickel is as strong as hardened steel. Understanding surfaces and interfaces is a key challenge for those working on nanomaterials, and one where new imaging and analysis instruments are vital.

What is nanotechnology?(2)

2009-06-11T19:51:00.000-07:00

2. New Materials: Nanomaterials

Much of nanoscience and many nanotechnologies are concerned with producing new or enhanced materials. Nanomaterials can be constructed by 'top down' techniques, producing very small structures from larger pieces of material, for example by etching to create circuits on the surface of a silicon microchip. They may also be constructed by 'bottom up' techniques, atom by atom or molecule by molecule. One way of doing this is self-assembly, in which the atoms or molecules arrange themselves into a structure due to their natural properties. Crystals grown for the semiconductor industry provide an example of self assembly, as does chemical synthesis of large molecules. A second way is to use tools to move each atom or molecule individually. Although this ‘positional assembly’ offers greater control over construction, it is currently very laborious and not suitable for industrial applications.It has been 25 years since the scanning tunneling microscope (STM) was invented, followed four years later by the atomic force microscope, and that's when nanoscience and nanotechnology really started to take off. Various forms of scanning probe microscopes based on these discoveries are essential for many areas of today's research. Scanning probe techniques have become the workhorse of nanoscience and nanotechnology research. Here is a Scanning Electron Microscope (SEM) image of a gold tip for Near-field Scanning Optical Microscopy (SNOM) obtained by Focussed Ion Beam (FIB) milling. The small tip at the center of the structure measures some tens of nanometers.
Current applications of nanoscale materials include very thin coatings used, for example, in electronics and active surfaces (for example, self-cleaning windows). In most applications the nanoscale components will be fixed or embedded but in some, such as those used in cosmetics and in some pilot environmental remediation applications, free nanoparticles are used. The ability to machine materials to very high precision and accuracy (better than 100nm) is leading to considerable benefits in a wide range of industrial sectors, for example in the production of components for the information and communication technology, automotive and aerospace industries.

What is nanotechnology? (1)

2009-06-11T11:08:00.000-07:00

What is nanotechnology?(1):> 1. The Significance of the Nanoscale(2):>2. New Materials: Nanomaterials(3):>2.1 Nanomaterials(4):>3. Nanomaterial Science(5):>3.1 Nanoscale in Two Dimensions(6):>3.2 Nanoscale in Two Dimensions(cont.)(7):>3.3 Nanoscale in Three Dimensions(cont.)(8):>3.4 Nanoscale in Three Dimensions(cont.)

The Significance of the Nanoscale

A nanometer (nm) is one thousand millionth of a meter. For comparison, a red blood cell is approximately 7,000 nm wide and a water molecule is almost 0.3nm across. People are interested in the nanoscale (which we define to be from 100nm down to the size of atoms (approximately 0.2nm)) because it is at this scale that the properties of materials can be very different from those at a larger scale. We define nanoscience as the study of phenomena and manipulation of materials at atomic, molecular and macromolecular scales, where properties differ significantly from those at a larger scale; and nanotechnologies as the design, characterisation, production and application of structures, devices and systems by controlling shape and size at the nanometer scale. In some senses, nanoscience and nanotechnologies are not new. Chemists have been making polymers, which are large molecules made up of nanoscale subunits, for many decades and nanotechnologies have been used to create the tiny features on computer chips for the past 20 years. However, advances in the tools that now allow atoms and molecules to be examined and probed with great precision have enabled the expansion and development of nanoscience and nanotechnologies.Watch an introduction to nanotechnology, starting with Richard Feynman's classic talk in December 1959 "There's Plenty of Room at the Bottom - An Invitation to Enter a New Field of Physics."

The bulk properties of materials often change dramatically with nano ingredients. Composites made from particles of nano-size ceramics or metals smaller than 100 nanometers can suddenly become much stronger than predicted by existing materials-science models. For example, metals with a so-called grain size of around 10 nanometers are as much as seven times harder and tougher than their ordinary counterparts with grain sizes in the hundreds of nanometers. The causes of these drastic changes stem from the weird world of quantum physics. The bulk properties of any material are merely the average of all the quantum forces affecting all the atoms. As you make things smaller and smaller, you eventually reach a point where the averaging no longer works. The properties of materials can be different at the nanoscale for two main reasons: First, nanomaterials have a relatively larger surface area when compared to the same mass of material produced in a larger form. This can make materials more chemically reactive (in some cases materials that are inert in their larger form are reactive when produced in their nanoscale form), and affect their strength or electrical properties. Second, quantum effects can begin to dominate the behaviour of matter at the nanoscale - particularly at the lower end - affecting the optical, electrical and magnetic behaviour of materials. Materials can be produced that are nanoscale in one dimension (for example, very thin surface coatings), in two dimensions (for example, nanowires and nanotubes) or in all three dimensions (for example, nanoparticles).

Source:>http://www.nanowerk.com/nanotechnology/introduction/introduction_to_nanotechnology_1.html

Nanomedicine

2009-06-11T01:57:00.000-07:00

Nanomedicine

From >Wikipedia, the free encyclopedia

Nanomedicine is the medical application of nanotechnology. The approaches to nanomedicine range from the medical use of nanomaterials, to nanoelectronic biosensors, and even possible future applications of molecular nanotechnology. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials.
Nanomedicine research is directly funded, with the US National Institutes of Health in 2005 funding a five-year plan to set up four nanomedicine centers. In April 2006, the journal Nature Materials estimated that 130 nanotech-based drugs and delivery systems were being developed worldwide.
Nanomedicine seeks to deliver a valuable set of research tools and clinically helpful devices in the near future.The National Nanotechnology Initiative expects new commercial applications in the pharmaceutical industry that may include advanced drug delivery systems, new therapies, and in vivo imaging.Neuro-electronic interfaces and other nanoelectronics-based sensors are another active goal of research. Further down the line, the speculative field of molecular nanotechnology believes that cell repair machines could revolutionize medicine and the medical field.
Nanomedicine is a large industry, with nanomedicine sales reaching 6.8 billion dollars in 2004, and with over 200 companies and 38 products worldwide, a minimum of 3.8 billion dollars in nanotechnology R&D is being invested every year.As the nanomedicine industry continues to grow, it is expected to have a significant impact on the economy.
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Drug delivery
Nanomedical approaches to drug delivery center on developing nanoscale particles or molecules to improve the bioavailability of a drug. Bioavailability refers to the presence of drug molecules where they are needed in the body and where they will do the most good. Drug delivery focuses on maximizing bioavailability both at specific places in the body and over a period of time. This will be achieved by molecular targeting by nanoengineered devices.It is all about targeting the molecules and delivering drugs with cell precision. More than $65 billion are wasted each year due to poor bioavailability. In vivo imaging is another area where tools and devices are being developed. Using nanoparticle contrast agents, images such as ultrasound and MRI have a favorable distribution and improved contrast. The new methods of nanoengineered materials that are being developed might be effective in treating illnesses and diseases such as cancer. What nanoscientists will be able to achieve in the future is beyond current imagination. This will be accomplished by self assembled biocompatible nanodevices that will detect, evaluate, treat and report to the clinical doctor automatically.
Drug delivery systems, lipid- or polymer-based nanoparticles, can be designed to improve the pharmacological and therapeutic properties of drugs.The strength of drug delivery systems is their ability to alter the pharmacokinetics and biodistribution of the drug. Nanoparticles have unusual properties that can be used to improve drug delivery. Where larger particles would have been cleared from the body, cells take up these nanoparticles because of their size. Complex drug delivery mechanisms are being developed, including the ability to get drugs through cell membranes and into cell cytoplasm. Efficiency is important because many diseases depend upon processes within the cell and can only be impeded by drugs that make their way into the cell. Triggered response is one way for drug molecules to be used more efficiently. Drugs are placed in the body and only activate on encountering a particular signal. For example, a drug with poor solubility will be replaced by a drug delivery system where both hydrophilic and hydrophobic environments exist, improving the solubility. Also, a drug may cause tissue damage, but with drug delivery, regulated drug release can eliminate the problem. If a drug is cleared too quickly from the body, this could force a patient to use high doses, but with drug delivery systems clearance can be reduced by altering the pharmacokinetics of the drug. Poor biodistribution is a problem that can affect normal tissues through widespread distribution, but the particulates from drug delivery systems lower the volume of distribution and reduce the effect on non-target tissue. Potential nanodrugs will work by very specific and well-understood mechanisms; one of the major impacts of nanotechnology and nanoscience will be in leading development of completely new drugs with more useful behavior and less side effects.

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Cancer
The small size of nanoparticles endows them with properties that can be very useful in oncology, particularly in imaging. Quantum dots (nanoparticles with quantum confinement properties, such as size-tunable light emission), when used in conjunction with MRI (magnetic resonance imaging), can produce exceptional images of tumor sites. These nanoparticles are much brighter than organic dyes and only need one light source for excitation. This means that the use of fluorescent quantum dots could produce a higher contrast image and at a lower cost than today's organic dyes used as contrast media. The downside, however, is that quantum dots are usually made of quite toxic elements.
Another nanoproperty, high surface area to volume ratio, allows many functional groups to be attached to a nanoparticle, which can seek out and bind to certain tumor cells. Additionally, the small size of nanoparticles (10 to 100 nanometers), allows them to preferentially accumulate at tumor sites (because tumors lack an effective lymphatic drainage system). A very exciting research question is how to make these imaging nanoparticles do more things for cancer. For instance, is it possible to manufacture multifunctional nanoparticles that would detect, image, and then proceed to treat a tumor? This question is under vigorous investigation; the answer to which could shape the future of cancer treatment.A promising new cancer treatment that may one day replace radiation and chemotherapy is edging closer to human trials. Kanzius RF therapy attaches microscopic nanoparticles to cancer cells and then "cooks" tumors inside the body with radio waves that heat only the nanoparticles and the adjacent (cancerous) cells.
Sensor test chips containing thousands of nanowires, able to detect proteins and other biomarkers left behind by cancer cells, could enable the detection and diagnosis of cancer in the early stages from a few drops of a patient's blood.
The basic point to use drug delivery is based upon three facts: a) efficient encapsulation of the drugs, b) successful delivery of said drugs to the targeted region of the body, and c) successful release of that drug there.
Researchers at Rice University under Prof. Jennifer West, have demonstrated the use of 120 nm diameter nanoshells coated with gold to kill cancer tumors in mice. The nanoshells can be targeted to bond to cancerous cells by conjugating antibodies or peptides to the nanoshell surface. By irradiating the area of the tumor with an infrared laser, which passes through flesh without heating it, the gold is heated sufficiently to cause death to the cancer cells.
Additionally, John Kanzius has invented a radio machine which uses a combination of radio waves and carbon or gold nanoparticles to destroy cancer cells.
Nanoparticles of cadmium selenide (quantum dots) glow when exposed to ultraviolet light. When injected, they seep into cancer tumors. The surgeon can see the glowing tumor, and use it as a guide for more accurate tumor removal.
One scientist, University of Michigan’s James Baker, believes he has discovered a highly efficient and successful way of delivering cancer-treatment drugs that is less harmful to the surrounding body. Baker has developed a nanotechnology that can locate and then eliminate cancerous cells. He looks at a molecule called a dendrimer. This molecule has over one hundred hooks on it that allow it to attach to cells in the body for a variety of purposes. Baker then attaches folic-acid to a few of the hooks (folic-acid, being a vitamin, is received by cells in the body). Cancer cells have more vitamin receptors than normal cells, so Baker's vitamin-laden dendrimer will be absorbed by the cancer cell. To the rest of the hooks on the dendrimer, Baker places anti-cancer drugs that will be absorbed with the dendrimer into the cancer cell, thereby delivering the cancer drug to the cancer cell and nowhere else (Bullis 2006).
In photodynamic therapy, a particle is placed within the body and is illuminated with light from the outside. The light gets absorbed by the particle and if the particle is metal, energy from the light will heat the particle and surrounding tissue. Light may also be used to produce high energy oxygen molecules which will chemically react with and destroy most organic molecules that are next to them (like tumors). This therapy is appealing for many reasons. It does not leave a “toxic trail” of reactive molecules throughout the body (chemotherapy) because it is directed where only the light is shined and the particles exist. Photodynamic therapy has potential for a noninvasive procedure for dealing with diseases, growths, and tumors.

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Surgery
At Rice University, a flesh welder is used to fuse two pieces of chicken meat into a single piece. The two pieces of chicken are placed together touching. A greenish liquid containing gold-coated nanoshells is dribbled along the seam. An infrared laser is traced along the seam, causing the two sides to weld together. This could solve the difficulties and blood leaks caused when the surgeon tries to restitch the arteries he/she has cut during a kidney or heart transplant. The flesh welder could meld the artery into a perfect.
-----------------------------------------------------------Visualization
Tracking movement can help determine how well drugs are being distributed or how substances are metabolized. It is difficult to track a small group of cells throughout the body so scientists used to dye the cells. These dyes needed to be excited by light of a certain wavelength in order for them to light up. While different color dyes absorb different frequencies of light, there was a need for as many light sources as cells. A way around this problem is with luminescent tags. These tags are quantum dots attached to proteins that penetrate cell membranes. The dots can be random in size, can be made of bio-inert material, and they demonstrate the nanoscale property that color is size-dependent. As a result, sizes are selected so that the frequency of light used to make a group of quantum dots fluoresce is an even multiple of the frequency required to make another group incandesce. Then both groups can be lit with a single light source

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Nanoparticle targeting
It is greatly observed that nanoparticles are promising tools for the advancement of drug delivery, medical imaging, and as diagnostic sensors.[who?] However, the biodistribution of these nanoparticles is mostly unknown due to the difficulty in targeting specific organs in the body. Current research in the excretory systems of mice, however, shows the ability of gold composites to selectively target certain organs based on their size and charge. These composites are encapsulated by a dendrimer and assigned a specific charge and size. Positively-charged gold nanoparticles were found to enter the kidneys while negatively-charged gold nanoparticles remained in the liver and spleen. It is suggested that the positive surface charge of the nanoparticle decreases the rate of osponization of nanoparticles in the liver, thus affecting the excretory pathway. Even at a relatively small size of 5 nm , though, these particles can become compartmentalized in the peripheral tissues, and will therefore accumulate in the body over time. While advancement of research proves that targeting and distribution can be augmented by nanoparticles, the dangers of nanotoxicity become an important next step in further understanding of their medical uses.
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Neuro-electronic interfaces
Neuro-electronic interfaces are a visionary goal dealing with the construction of nanodevices that will permit computers to be joined and linked to the nervous system. This idea requires the building of a molecular structure that will permit control and detection of nerve impulses by an external computer. The computers will be able to interpret, register, and respond to signals the body gives off when it feels sensations. The demand for such structures is huge because many diseases involve the decay of the nervous system (ALS and multiple sclerosis). Also, many injuries and accidents may impair the nervous system resulting in dysfunctional systems and paraplegia. If computers could control the nervous system through neuro-electronic interface, problems that impair the system could be controlled so that effects of diseases and injuries could be overcome. Two considerations must be made when selecting the power source for such applications. They are refuelable and nonrefuelable strategies. A refuelable strategy implies energy is refilled continuously or periodically with external sonic, chemical, tethered, magnetic, or electrical sources. A nonrefuelable strategy implies that all power is drawn from internal energy storage which would stop when all energy is drained.
One limitation to this innovation is the fact that electrical interference is a possibility. Electric fields, electromagnetic pulses (EMP), and stray fields from other in vivo electrical devices can all cause interference. Also, thick insulators are required to prevent electron leakage, and if high conductivity of the in vivo medium occurs there is a risk of sudden power loss and “shorting out.” Finally, thick wires are also needed to conduct substantial power levels without overheating. Little practical progress has been made even though research is happening. The wiring of the structure is extremely difficult because they must be positioned precisely in the nervous system so that it is able to monitor and respond to nervous signals. The structures that will provide the interface must also be compatible with the body’s immune system so that they will remain unaffected in the body for a long time.In addition, the structures must also sense ionic currents and be able to cause currents to flow backward. While the potential for these structures is amazing, there is no timetable for when they will be available.

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Medical applications of molecular nanotechnology
Molecular nanotechnology is a speculative subfield of nanotechnology regarding the possibility of engineering molecular assemblers, machines which could re-order matter at a molecular or atomic scale. Molecular nanotechnology is highly theoretical, seeking to anticipate what inventions nanotechnology might yield and to propose an agenda for future inquiry. The proposed elements of molecular nanotechnology, such as molecular assemblers and nanorobots are far beyond current capabilities.
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Nanorobots
The somewhat speculative claims about the possibility of using nanorobots in medicine, advocates say, would totally change the world of medicine once it is realized. Nanomedicine would make use of these nanorobots (e.g., Computational Genes), introduced into the body, to repair or detect damages and infections. According to Robert Freitas of the Institute for Molecular Manufacturing, a typical blood borne medical nanorobot would be between 0.5-3 micrometres in size, because that is the maximum size possible due to capillary passage requirement. Carbon would be the primary element used to build these nanorobots due to the inherent strength and other characteristics of some forms of carbon (diamond/fullerene composites), and nanorobots would be fabricated in desktop nanofactories specialized for this purpose.
Nanodevices could be observed at work inside the body using MRI, especially if their components were manufactured using mostly 13C atoms rather than the natural 12C isotope of carbon, since 13C has a nonzero nuclear magnetic moment. Medical nanodevices would first be injected into a human body, and would then go to work in a specific organ or tissue mass. The doctor will monitor the progress, and make certain that the nanodevices have gotten to the correct target treatment region. The doctor will also be able to scan a section of the body, and actually see the nanodevices congregated neatly around their target (a tumor mass, etc.) so that he or she can be sure that the procedure was successful.
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Cell repair machines
Using drugs and surgery, doctors can only encourage tissues to repair themselves. With molecular machines, there will be more direct repairs. Cell repair will utilize the same tasks that living systems already prove possible. Access to cells is possible because biologists can stick needles into cells without killing them. Thus, molecular machines are capable of entering the cell. Also, all specific biochemical interactions show that molecular systems can recognize other molecules by touch, build or rebuild every molecule in a cell, and can disassemble damaged molecules. Finally, cells that replicate prove that molecular systems can assemble every system found in a cell. Therefore, since nature has demonstrated the basic operations needed to perform molecular-level cell repair, in the future, nanomachine based systems will be built that are able to enter cells, sense differences from healthy ones and make modifications to the structure.
The possibilities of these cell repair machines are impressive. Comparable to the size of viruses or bacteria, their compact parts would allow them to be more complex. The early machines will be specialized. As they open and close cell membranes or travel through tissue and enter cells and viruses, machines will only be able to correct a single molecular disorder like DNA damage or enzyme deficiency. Later, cell repair machines will be programmed with more abilities with the help of advanced AI systems.
Nanocomputers will be needed to guide these machines. These computers will direct machines to examine, take apart, and rebuild damaged molecular structures. Repair machines will be able to repair whole cells by working structure by structure. Then by working cell by cell and tissue by tissue, whole organs can be repaired. Finally, by working organ by organ, health is restored to the body. Cells damaged to the point of inactivity can be repaired because of the ability of molecular machines to build cells from scratch. Therefore, cell repair machines will free medicine from reliance on self repair.
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Nanonephrology
Nanonephrology is a branch of nanomedicine and nanotechnology that deals with 1) the study of kidney protein structures at the atomic level; 2) nano-imaging approaches to study cellular processes in kidney cells; and 3) nano medical treatments that utilize nanoparticles and to treat various kidney diseases.
The creation and use of materials and devices at the molecular and atomic levels that can be used for the diagnosis and therapy of renal diseases is also a part of Nanonephrology that will play a role in the management of patients with kidney disease in the future. Advances in Nanonephrology will be based on discoveries in the above areas that can provide nano-scale information on the cellular molecular machinery involved in normal kidney processes and in pathological states. By understanding the physical and chemical properties of proteins and other macromolecules at the atomic level in various cells in the kidney, novel therapeutic approaches can be designed to combat major renal diseases. The nano-scale artificial kidney is a goal that many physicians dream of. Nano-scale engineering advances will permit programmable and controllable nano-scale robots to execute curative and reconstructive procedures in the human kidney at the cellular and molecular levels. Designing nanostructures compatible with the kidney cells and that can safely operate in vivo is also a future goal. The ability to direct events in a controlled fashion at the cellular nano-level has the potential of significantly improving the lives of patients with kidney diseases.

NanoMission

2009-06-11T00:16:00.000-07:00

Nanomedicine Vesicle
Nanocomputers will be needed to guide these machines. These computers will direct machines to examine, take apart, and rebuild damaged molecular structures. Repair machines will be able to repair whole cells by working structure by structure. Then by working cell by cell and tissue by tissue, whole organs can be repaired. Finally, by working organ by organ, health is restored to the body. Cells damaged to the point of inactivity can be repaired because of the ability of molecular machines to build cells from scratch. Therefore, cell repair machines will free medicine from reliance on self repair. A new wave of technology and medicine is being created and its impact on the world is going to be monumental. From the possible applications such as drug delivery and in vivo imaging to the potential machines of the future, advancements in nanomedicine are being made every day. It will not be long for the 10 billion dollar industry to explode into a 100 billion or 1 trillion dollar industry, and drug delivery, in vivo imaging and therapy is just the beginning.

Source:>Wilkepedia

Future Medicine

2009-06-11T00:12:00.000-07:00

The photonic nanomedicine revolution:
Let the human side of nanotechnology emerge
Naomi J Halas

Department of Electrical & Computer Engineering & the Laboratory for Nanophotonics,
Rice University, 6100 Main St., Houston, TX 77005-1892, USA. halas@rice.edu

Nanoparticle-based photothermal ablation is showing extraordinary promise as an unusually effective and potentially revolutionary cancer therapy. This approach uses light at near-infrared wavelengths that pass through tissue, in combination with gold-based nanoparticles specifically engineered to absorb that light and convert it to heat. The light-absorbing nanoparticles serve as highly localized heat sources that destroy cells in their immediate vicinity by hyperthermia [4]. This method has been shown to be highly effective in extensive animal studies, with tumor remission rates above 90%. Extensive toxicity studies have been performed on nanoshells, the nanoparticles most utilized to date in these studies, and this is being followed by similar studies on other types of noble metal nanoparticles that are also promising candidates for this therapeutic modality. The US FDA has recently granted approval for initial human trials of this therapy for head and neck cancer. Given the extraordinary promise of these potentially revolutionary therapeutic nanodevices and their impending availability, research into nanoparticle-based therapeutics is beginning to move into the next critical phase: the development of nanoparticle-assisted therapeutic practices specifically for clinical use.
One of the most extraordinary aspects of nanoparticle-assisted photothermal therapy for tumor remission is that it is drug free: cell death is induced by the localized heat generated when the nanoparticles absorb near-infrared light. This is an exceedingly important aspect: with heat as the source of cell death, this approach is independent of the specifics of the immune systems of various animals on which it may be tested. This also means that with this therapeutic approach, the nanoparticles can be classified as a device, rather than a drug. They are nanoscale lenses, delivering highly focused light to cancer cells or within tumors much like a lens that captures sunlight delivers enough heat to a leaf to enable it to burst into flames. However, in the case of nanoparticle-based photothermal therapy, the heat required to induce cell death is only approximately 15–20? above physiological temperatures. Because the nanoparticles are devices and not drugs, operating only on heat and light and not interacting chemically with living systems, this therapy, and other variants of this approach, may be available for patients and practitioners in just a few years.
For cancer, this nanoparticle-based strategy will ultimately allow the clinician to remove localized tumors with a simple, minimally invasive, nonsurgical procedure performed, for example, with a portable laser in an outpatient clinic instead of a surgical suite. This could fundamentally revolutionize the treatment of virtually all soft-tissue cancers, transforming this feared, life-threatening disease to an actively managed illness that can be treated and contained prophylactically.
While early detection and treatment of localized, noninvasive tumors is ideal, in reality it is not the typical diagnostic scenario. In any given year, invasive carcinoma diagnoses far outnumber the diagnosed cases of localized cancer. While nanoparticle-based photothermal therapy appears to be highly promising for the removal of localized tumors, an important and immediate challenge is to develop strategies to address more advanced stages of cancer with this powerful new modality. The proliferation of cancer to the lymph nodes directly adjacent to the primary tumor is a key diagnostic for cancer clinicians, and determines the course of treatment. In conventional surgery, these adjacent lymph nodes are typically removed along with the primary tumor. Recent advances in the development of strongly enhanced fluorescent markers for deep-tissue imaging may make resolution at the limit of a few cells possible. Targeted imaging of cancer in lymph nodes, to quantify the proliferation of cancer beyond carcinoma in situ, could be combined with photothermal destruction of targeted cancer cells using nanoparticle-based probes. This would provide a method for removing the cancer cells in the lymph nodes while preserving, largely intact, the lymphatic system of the cancer patient. As markers become available this general approach should be extendable to additional strategies for the treatment of metastatic disease.
The centers of solid tumors are frequently observed to be largely necrotic, resulting from prolonged hypoxia: insufficient availability of oxygen and glucose to meet the metabolic demands of the malignant cells. Because of the decreased blood flow in these tumor regions, they are inaccessible by, and therefore highly resistant to, conventional chemotherapies. One possible scenario for the progression of cancer to its latter, highly fatal stages is that cells surviving in these inaccessible hypoxic regions may themselves be the source of subsequent local recurrence and distant metastasis. One of the body’s responses to the presence of a malignant neoplasm is to recruit peripheral blood monocytes into the tumor, which then differentiate into macrophages. These cells have been shown to promote metastatic disease. One potentially promising scenario is to induce uptake of nanoshells into monocytes, which are then recruited into the hypoxic regions of tumors: the presence of the nanoshells would then permit photothermal destruction of the necrotic region. This type of approach may provide a critical new strategy for thwarting tumor metastasis.
An exciting new use of nanoparticle-assisted photothermal therapy is in delivery methods for gene therapy. It is widely recognized that gene-based therapies hold extraordinary therapeutic promise for cancer: many genetic markers have been discovered, and numerous DNA-based therapeutics have been proposed for the targeting of pathogenic genes for various cancers. Genetic vaccines have also been suggested for certain forms of cancer now believed to have a hereditary basis, such as the 42–57% of prostate cancer cases that correlate with inherited genetic factors. However, while the discovery of gene targets and the development of gene-based therapies at the molecular level has been pursued aggressively for more than 15 years, the transition of these therapies from the research laboratory to the clinic is at a virtual impasse and fraught with severe challenges. Unprotected gene therapy drugs (DNA- or RNA-based) introduced into the bloodstream are rapidly broken down, preventing their diffusion to the region of disease. Viruses, the initial carrier of choice in most gene therapy research, present a variety of potential problems to the patient – toxicity, immune and inflammatory responses, and gene control and targeting issues. The first clinical gene therapy studies utilizing a viral delivery vector resulted in patient death, and had to be terminated in their initial stage. There is a clear critical need for nonviral delivery vectors for gene therapy for this field to advance towards its many clinical applications. Nanoparticle–biomolecule light-actuated complexes are being developed and tested with clinically relevant genetic markers. For example, by combining gold nanoparticles with specific oligonucleotides, the nanoparticle complex can serve as a nonviral gene-delivery vector, where incident light can trigger the release of the nucleotide once the complex has been taken up by cells. Initial release data in cell culture studies show that this approach has outstanding promise for gene delivery. Light-triggered nucleotide release from these nanoparticle–molecule complexes makes them particularly well suited for the localized administration of gene therapy drugs into the tissue or organ of interest.
In conclusion, nanoparticle-assisted, photothermal therapeutic strategies have the capability of providing revolutionary tools in many battles against human disease, with the clear potential for highly effective therapy for cancer and other diseases. Moreover, this approach is unparalleled in its level of noninvasiveness and in its low, essentially nonexistent toxicity. The long-term impact of the development of these new treatment methods will be to change the way we treat cancer. This approach may also provide effective new strategies for treatments of other, lesser known and less-studied diseases such as autoimmune disorders, where few or no treatment options currently exist. In addition to increased efficacy, an extraordinary advantage of nanoparticle-assisted photothermal therapy is that essentially no, or minimal, side effects are expected. Replacing current chemotherapy treatments, with their high level of systemic toxicity and deleterious side effects, with this benign therapeutic approach will greatly increase the quality of life for cancer patients and their families.
Financial & competing interests disclosure The author is the inventor of nanoshells and pioneered nanoparticle-based photothermal therapies along with her collaborators at Rice University (TX, USA), J West and R Drezek. She is the co-founder of Nanospectra Biosciences, Inc. (www.nanospectra.com), a Houston-based company dedicated to the translation of this therapeutic approach into clinical practice. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Source >http://www.futuremedicine.com/doi/full/10.2217/nnm.09.26

Biomedical devices

2009-06-10T23:50:00.000-07:00

The devices considered in this section fall into the category of nanobiotechnology, also known as nanomedicine, defined as the application of nanotechnology to human health.One of the most attractive candidate tasks for a radically new approach is the sequencing ofthe human genome. The growing fund of medical experience concerning individual patients’responses to pharmaceutical drugs is revealing significant differences between individuals, whichin many cases might be due to differences in DNA sequence. Despite the tremendousboost to the technology of DNA sequencing that came from the international project to sequencethe (putatively prototypical) human genome, the basic methods applied were the conventionalbiochemical ones; the vast increase in throughput was achieved through massive parallelizationand automation.
The four different DNA “bases” (or nucleotides, symbolized as A,C,G,T) differ not only in the chemical nature, but also in their physical nature, most significantly as regards size and shape.One of the early motivations for developing the atomic force microscope was the hope that thesephysical differences could be revealed by rapidly scanning a single strand of DNA. Although theresolution, at least in the presence of liquid water, has so far proved to be inadequate, alternativeapproaches with the same end in view are being intensively investigated. The favoured schemeis to pass the DNA strand through a nanopore while measuring ionic conductance (of theelectrolyte solution in which the DNA is dissolved), either along or across the pore, with theresolution of a single base. The different nucleotides can be thus distinguished, but it is difficultto capture the DNA and drive it through the pore.
The flagship nanomedical system (rather than device) is the “nanobot”, an autonomous robotenvisaged to be about the size of a bacterium (i.e., about one micrometre in diameter), andcontaining many nanodevices (an energy source, a means of propulsion, an information pro-cessor, environmental sensors, and so forth). When engineering such devices it is importantto note the environment in which they must operate: viscous (highly dissipative), dominatedby friction and fluctuations (Brownian motion), and in which inertia plays a negligible role.This is in contrast to the familiar macroscopic mechanisms that follow Newton’s laws: for thenanobot, force is not given by the product of mass and acceleration, but by the product of thecoefficient of friction and its velocity, together with superimposed random fluctuations. Anyself-propelling nanobot is therefore likely to resemble a motile bacterium rather than a deviceequipped with nanoscale oars or paddles.
Source: Jeremy Rameden," Nanotechnology " 2009

Trends in Biomedical Nanotechnology(1)

2009-06-10T00:21:00.000-07:00

Trends in Biomedical Nanotechnology Programs Worldwide

By Mark Morrison and Ineke Malsch

An overview of trends in nanotechnology research programs for biomedical applications in the United States, leading European countries, and Japan. We focus on technologies for applications inside the body, including drug delivery technologies for pharmaceuticals, and new materials and technologies for prostheses and implants. We also include technologies for applications outside the body including diagnostics and high throughput screening of drug compounds. We cover the main application areas in pharmaceuticals and medical devices — areas where governments expect nanotechnology to make important contributions. We also outline the currently operational national and European Union (EU) policies and programs intended to stimulate the development of biomedical nanotechnology in the U.S., Europe, and Japan.
Several applications of nanotechnology are already available in the market. Lipid spheres (liposomes) with diameters of 100 nm are available for carrying anticancer drugs inside the body. Some anti-fungal foot sprays contain nanoscale zinc oxide particles to reduce clogging.

Nanotechnology is producing short-term impacts in the areas of:

Medical diagnostic tools and sensors
Drug delivery
Catalysts (many applications in chemistry and pharmaceuticals)
Alloys (e.g., steel and materials used in prosthetics) Improved and body-friendly implants
Biosensors and chemical sensors
Bioanalysis tools Bioseparation technologies Medical imaging
Filters

Most current applications utilize nanopowder qualities instead of other properties present at the nanoscale. The next stage of applications of nanotechnology will allow products to exhibit more unusual properties as product creation is approached from the bottom up. This is considered a measure of the development of nanotechnology. Long-term product and application perspectives of nanotechnology with high future market potentials include:

Perfect selective sensors for the control of environment, food, and body functions Pharmaceuticals that have long-term dosable capabilities and can be taken orally Replacements for human tissues and organs
Economical or reusable diagnostic chips for preventive medical surveys

It is estimated that more than 300 companies in Europe are involved in nano- technology as their primary areas of business, and many more companies, particu- larly larger organizations, are pursuing some activities in the field. Large organiza- tions currently exploring the possibilities of nanotechnology with near-term applications in drug delivery are Biosante, Akzo Nobel, Ciba, Eli Lilly, and Merck.

Source:Biomedical nanotechnology / edited by Neelina H. Malsch

CLOSING REMARKS

2009-06-10T00:16:00.000-07:00

Nanotechnology and Biomedicine(8)
Source: Neelina H. Malsch_Biomedical Nanotechnology

Nanoscale and biosystem research areas are merging with information technol- ogy and cognitive science, leading to completely new science and technology plat- forms in genome pharmaceuticals, biosystem-on-a-chip devices, regenerative medicine, neuroscience, and food systems. A key challenge is bringing together biologists and doctors with scientists and engineers interested in the new measure- ment and fabrication capabilities of nanotechnology. Another key challenge is fore- casting and addressing possible unexpected consequences of the revolutionary sys- tems and engineering developments utilized in nanobiosystems. Priority science and technology goals may be envisioned for iternational collaboration in nanoscale research and education, better comprehension of nature, increasing productivity, sustainable development, and addressing humanity and civilization issues.The confluence of biology, medicine, and nanotechnology is reflected in gov- ernment funding programs and science policies. For example, the U.S. NNI plans to increase its contributions to programs dedicated to nanobiosystems beyond the current level of about 15%; similar trends in other countries intended to better recognize nanobiosystems research have also been noted.Nanoscale assemblies of organic and inorganic matter lead to the formation of cells and other activities of the most complex known systems — the human brain and body. Nanotechnology plays a key role in understanding these processes and the advancement of biological sciences, biotechnology, and medicine. Four chapters in this volume present key issues of molecular medicine, from drug delivery and biocompatible replacement body parts to devices and systems for high throughput diagnostics and biodefense. Three other chapters provide overviews on relevant research and development programs, the social and economic contexts, and potential uncertainties surrounding nanobiomedical developments. This broad perspective is of interest not only to the scientific and medical community, but also to science policy makers, social scientists, economists, and the public.

FUNDING AND POLICY IMPLICATIONS

2009-06-10T00:14:00.001-07:00

Nanotechnology and Biomedicine(8)
Source: Neelina H. Malsch_Biomedical Nanotechnology

With proper attention to ethical issues and societal needs, these converging technologies could allow tremendous improvements in human capabilities, societal outcomes, and the quality of life. Malsch (Chapter 6) examines the potential of nanotechnology to address health care needs and the societal implications of nano- biomedical research and development. The most important avenues of disease treat- ment and the main issues to be considered by governments, civic organizations, and the public are evaluated. The social, economic, ethical, and legal aspects are integral parts of nanotechnology R&D for biomedical applications.Schuler reviews the potential risks of biomedical nanotechnology and outlines several scenarios for eventual regulation via market forces, extensions of current regulations, accidents, regulatory capture, self-regulation, or technology ban. The chances of success of these scenarios are determined by the way the stakeholders respond to the large-scale production and commercialization expected to begin within the next decade.The United States initiated a multidisciplinary strategy for development of sci- ence and engineering fundamentals through its NNI in 2000. Japan and Europe now have broad programs and plans for the next 4 or 5 years. More than 40 countries have developed programs or focused projects in nanotechnology since 2000. Research on biosystems has received larger support in the United States, the United Kingdom, Germany, Switzerland, and Japan. Other significant investments in nano- technology research programs with contributions to nanobiosystems have been made by the European Community, Australia, Taiwan, Canada, Finland, Italy, Israel, Sin- gapore, and Sweden. Relatively large programs in nanotechnology but with small biosystems components until 2004 have been developed by South Korea and China. Worldwide government funding has increased to about eight times what it was in1997, exceeding $3.6 billion in 2004 (see http://www.nsf.gov/nano). Differences among countries can be noted by the research domains they choose, the levels of program integration into various industrial sectors, and the time scales of their R&D targets. Of the total NNI investment in 2004, about 15% is dedicated to nanobiosystems in two ways. First, the implementation plan of NNI focuses on fundamental research related to nanobiosystems and nanomedicine. Second, the program involves two grand challenges related to health issues and bionanodevices. Additional investments have been made for development of infrastructures at various NSF centers, including the Cornell University Nanotechnology Center and additional nanoscale science and engineering centers at Rice University, the University of Pennsylvania, and Ohio State University.The NNI was evaluated by the National Research Council and the council published its findings in June 2002. One recommendation was to expand research at the interface of nanoscale technology with biology, biotechnology, and life sci- ences. Such plans to extend nanobiosystems research are under way at the U.S. Department of Energy (DOE), the National Institutes of Health (NIH), the National Science Foundation (NSF), and the Department of Agriculture (USDA). A NSF–Department of Commerce (DOC) report recommends a focus on improving physical and mental human performance through converging technologies.2 The NSF, the National Aeronautics & Space Administration (NASA), and the Department of Defense (DOD) have included aspects of converging technologies and improving human performance in their program solicitations. The Defense Advanced Research Projects Agency (DARPA) instituted a program on engineered biomolecular nan- odevices and systems. A letter sent to the NIH director by seven US senators in2003 recommended that the NIH increase funding in nanotechnology. The White House budget request for fiscal 2004 lists “nanobiosystems for medical advances and new products” as a priority within the NNI. Nanobiotechnology RRD is high- lighted in the long-term NNI Strategic Plan published in December 2004 (http://www.nano.gov). Public interactions provide feedback for the societal accep- tance of nanotechnology, and particularly the aspects related to human dimensions and nanobiotechnology.10,11Nanobiosystems is an area of interest recognized by various international studies on nanotechnology, such as those prepared by Asia-Pacific Economic Council (APEC),12 the Meridian Institute,13 and Economic Organization of Developed Coun- tries (OECD).14 In a survey performed by the United Kingdom Institute of Nano- technology and by OECD,14 experts identified the locations of the most sophisticated nanotechnology developments in the medical and pharmaceutical areas in the United States (48%), the United Kingdom (20%), Germany (17%), Switzerland (8%), Swe- den (4%), and Japan (3%). The U.S. NNI plans to devote about 15% of its fiscal year 2004 budget to nanobiosystems; Germany will allocate about 10% and France about 8%. The biology route to nanotechnology may be a choice for countries with less developed economies because required research facility investments are lower.

FUNDING AND POLICY IMPLICATIONS

2009-06-10T00:14:00.000-07:00

Nanotechnology and Biomedicine(8)

Source: Neelina H. Malsch_Biomedical Nanotechnology

With proper attention to ethical issues and societal needs, these converging technologies could allow tremendous improvements in human capabilities, societal outcomes, and the quality of life. Malsch (Chapter 6) examines the potential of nanotechnology to address health care needs and the societal implications of nano- biomedical research and development. The most important avenues of disease treat- ment and the main issues to be considered by governments, civic organizations, and the public are evaluated. The social, economic, ethical, and legal aspects are integral parts of nanotechnology R&D for biomedical applications.Schuler reviews the potential risks of biomedical nanotechnology and outlines several scenarios for eventual regulation via market forces, extensions of current regulations, accidents, regulatory capture, self-regulation, or technology ban. The chances of success of these scenarios are determined by the way the stakeholders respond to the large-scale production and commercialization expected to begin within the next decade.The United States initiated a multidisciplinary strategy for development of sci- ence and engineering fundamentals through its NNI in 2000. Japan and Europe now have broad programs and plans for the next 4 or 5 years. More than 40 countries have developed programs or focused projects in nanotechnology since 2000. Research on biosystems has received larger support in the United States, the United Kingdom, Germany, Switzerland, and Japan. Other significant investments in nano- technology research programs with contributions to nanobiosystems have been made by the European Community, Australia, Taiwan, Canada, Finland, Italy, Israel, Sin- gapore, and Sweden. Relatively large programs in nanotechnology but with small biosystems components until 2004 have been developed by South Korea and China. Worldwide government funding has increased to about eight times what it was in1997, exceeding $3.6 billion in 2004 (see http://www.nsf.gov/nano). Differences among countries can be noted by the research domains they choose, the levels of program integration into various industrial sectors, and the time scales of their R&D targets. Of the total NNI investment in 2004, about 15% is dedicated to nanobiosystems in two ways. First, the implementation plan of NNI focuses on fundamental research related to nanobiosystems and nanomedicine. Second, the program involves two grand challenges related to health issues and bionanodevices. Additional investments have been made for development of infrastructures at various NSF centers, including the Cornell University Nanotechnology Center and additional nanoscale science and engineering centers at Rice University, the University of Pennsylvania, and Ohio State University.The NNI was evaluated by the National Research Council and the council published its findings in June 2002. One recommendation was to expand research at the interface of nanoscale technology with biology, biotechnology, and life sci- ences. Such plans to extend nanobiosystems research are under way at the U.S. Department of Energy (DOE), the National Institutes of Health (NIH), the National Science Foundation (NSF), and the Department of Agriculture (USDA). A NSF–Department of Commerce (DOC) report recommends a focus on improving physical and mental human performance through converging technologies.2 The NSF, the National Aeronautics & Space Administration (NASA), and the Department of Defense (DOD) have included aspects of converging technologies and improving human performance in their program solicitations. The Defense Advanced Research Projects Agency (DARPA) instituted a program on engineered biomolecular nan- odevices and systems. A letter sent to the NIH director by seven US senators in2003 recommended that the NIH increase funding in nanotechnology. The White House budget request for fiscal 2004 lists “nanobiosystems for medical advances and new products” as a priority within the NNI. Nanobiotechnology RRD is high- lighted in the long-term NNI Strategic Plan published in December 2004 (http://www.nano.gov). Public interactions provide feedback for the societal accep- tance of nanotechnology, and particularly the aspects related to human dimensions and nanobiotechnology.10,11Nanobiosystems is an area of interest recognized by various international studies on nanotechnology, such as those prepared by Asia-Pacific Economic Council (APEC),12 the Meridian Institute,13 and Economic Organization of Developed Coun- tries (OECD).14 In a survey performed by the United Kingdom Institute of Nano- technology and by OECD,14 experts identified the locations of the most sophisticated nanotechnology developments in the medical and pharmaceutical areas in the United States (48%), the United Kingdom (20%), Germany (17%), Switzerland (8%), Swe- den (4%), and Japan (3%). The U.S. NNI plans to devote about 15% of its fiscal year 2004 budget to nanobiosystems; Germany will allocate about 10% and France about 8%. The biology route to nanotechnology may be a choice for countries with less developed economies because required research facility investments are lower.

NANOTECHNOLOGY PLATFORMS FOR BIOMEDICINE

2009-06-10T00:13:00.000-07:00

Nanotechnology and Biomedicine(7)
Source: Neelina H. Malsch_Biomedical Nanotechnology

Nanotechnology offers new solutions for the transformation of biosystems and provides a broad technological platform for applications in industry; such applica- tions include bioprocessing, molecular medicine (detection and treatment of ill- nesses, body part replacement, regenerative medicine, nanoscale surgery, synthesis and targeted delivery of drugs), environmental improvement (mitigation of pollution and ecotoxicology), improving food and agricultural systems (enhancing agricultural output, new food products, food conservation), and improving human performance (enhancing sensorial capacity, connecting brain and mind, integrating neural systems with nanoelectronics and nanostructured materials).Nanotechnology will also serve as a technological platform for new develop- ments in biotechnology; for example, biochips, “green” manufacturing (biocompat- ibility and biocomplexity aspects), sensors for astronauts and soldiers, biofluidics for handling DNA and other molecules, in vitro fertilization for livestock, nanofil- tration, bioprocessing by design, and traceability of genetically modified foods.Exploratory areas include understanding, conditioning, and repairing brain and other parts for regaining cognition, pharmaceuticals and plant genomes, synthesis of more effective and biodegradable chemicals for agriculture, implantable detectors, and use of saliva instead of blood for detection of illnesses. Broader issues include economic molecular medicine, sustainable agriculture, conservation of biocomplex- ity, and enabling emerging technologies. Measurements of biological entities such as neural systems may be possible at the level of developing interneuronal synapse circuits and their 20-nm diameter synoptic vesicles. Other potential breakthroughs that may be targeted by the research community in the next 10 years are the detection and treatment of cancer, treatment of brain illnesses, understanding and addressing chronic illnesses, improving human sensorial capacity, maintaining quality of life throughout the aging process, and enhancing learning capabilities.

DIAGNOSTICS AND SCREENING

2009-06-10T00:12:00.000-07:00

Nanotechnology and Biomedicine(6)
Source: Neelina H. Malsch_Biomedical Nanotechnology

Del Campo and Bruce review the potential of nanotechnology for high throughput screening. The complexity and diversity of biomolecules and the range of external agents affecting biomolecules underline the importance of this capability. The current approaches and future trends are outlined for various groups of diseases, tissue lapping, and therapeutics. The most successful methods are based on flat surface and fiberoptic microarrays, microfluidics, and quantum dots.Nanoscale sensors and their integration into biological and chemical detection devices for defense purposes are reviewed by Shipbaugh et al.Typical threats and solutions for measuring, networking, and transmitting information are presented. Airborne and contact exposures can be evaluated using nanoscale princi- ples of operation for sensing. Key challenges for future research for biological and chemical detection are outlined.One example of the complexity of the scientific issues identified at the interface between synthetic and biological materials and systems is the study of toxicity caused by dendrimers. Generation dendrimers of particular diameters and electrically and positively charged can actually rip lipid bilayers from cells to form micellar- like structures, leading to cytotoxicity. The health concerns caused by nanotechnology products must receive full consideration from the private sector and government organizations because of the specific properties and types of complex interactions at the nanoscale.

IMPLANTS AND PROSTHESES

2009-06-10T00:11:00.000-07:00

Nanotechnology and Biomedicine(5)
Source: Neelina H. Malsch_Biomedical Nanotechnology

Van den Beucken et al.demonstrates how nanotechnology approaches for biocompatible implants and prostheses become more relevant as life expectancy increases. The main challenges are the synthesis of biocompatible mate- rials, understanding and eventually controlling the biological processes that occur upon implantation of natural materials and synthetic devices, and identifying future applications of biomedical nanotechnology to address various health issues. The use of currently available nanofabrication methods for implants and understanding cell behavior when brought in contact with nanostructured materials are also described.

DRUG SYNTHESIS AND DELIVERY

2009-06-10T00:10:00.000-07:00

Nanotechnology and Biomedicine(4)
Source: Neelina H. Malsch_Biomedical Nanotechnology

Yamamoto discusses the new contributions of nanotechnology in com- parison to existing methods to release, target, and control drug delivery inside the human body. Self-assembly and self-organization of matter offer new pathways for achieving desired properties and functions. Exploiting nanoparticle sizes and nanosized gaps between structures represent other ways of obtaining new properties and physical access inside tissues and cells. Quantum dots are used for visualization in drug delivery because of their fluorescence and ability to trace very small biological structures. The secondary effects of the new techniques include raising safety concerns such as toxicity that must be addressed before the techniques are used in medical practice.

TOWARD MOLECULAR MEDICINE

2009-06-10T00:08:00.000-07:00

Nanotechnology and Biomedicine(3)
Source: Neelina H. Malsch_Biomedical Nanotechnology

Nanotechnology provides investigation tools and technology platforms for bio- medicine. Examples include working in the subcellular environment, investigating and transforming nanobiosystems (for example, the nervous system) rather than individual nanocomponents, and developing new nanobiosensor platforms. Investi- gative methods of nanotechnology have made inroads in uncovering fundamental biological processes, including self-assembling, subcellular processes, and system biology (for example, the biology of the neural system).Key advancements have been made in measurements at the molecular and sub- cellular levels and in understanding the cell as a highly organized molecular mech- anism based on its abilities of information utilization, self-organization, self-repair, and self-replication.4 Single molecule measurements are shedding light on the dynamic and mechanistic properties of molecular biomachines, both in vivo and in vitro, allowing direct investigation of molecular motors, enzyme reactions, protein dynamics, DNA transcription, and cell signaling. Chemical composition has been measured within a cell in vivo.Another trend is the transition from understanding and control of a single nano- structure to nanosystems. We are beginning to understand the interactions of sub- cellular components and the molecular origins of diseases. This has implications in the areas of medical diagnostics, treatments, and human tissue replacements. Spatial and temporal interactions of cells including intracellular forces have been measured. Atomic force microscopy has been used to measure intermolecular binding strength of a pair of molecules in a physiological solution, providing quantitative evidence of their cohesive function.5 Flows and forces around cells have been quantitatively determined, and mechanics of biomolecules are better understood.6 It is accepted that cell architecture and macro behavior are determined by small-scale intercellular interactions.Other trends include the ability to detect molecular phenomena and build sensors and systems of sensors that have high degrees of accuracy and cover large domains. Fluorescent semiconductor nanoparticles or quantum dots can be used in imaging as markers for biological processes because they photobleach much more slowly than dye molecules and their emission wave lengths can be finely tuned. Key challenges are the encapsulation of nanoparticles with biocompatible layers and avoiding non- specific adsorption. Nanoscience investigative tools help us understand self-organiza- tion, supramolecular chemistry and assembly dynamics, and self-assembly of nano- scopic, mesoscopic, and even macroscopic components of living systems.7Emerging areas include developing realistic molecular modeling for “soft” mat- ter,8 obtaining nonensemble-averaged information at the nanoscale, understanding energy supply and conversion to cells (photons and lasers), and regeneration mech- anisms. Because the first level of organization of all living systems is at the nanoscale,it is expected that nanotechnology will affect almost all branches of medicine. This volume discusses important contributions in key areas. In Chapter 1, Morrison and Malsch discuss worldwide trends in biomedical nanotechnology programs. They cover the efforts of governments, academia, research organizations, and other entities related to biomedical nanotechnology.

Nanotechnology and Biomedicine(2)

2009-06-10T00:07:00.000-07:00

Nanotechnology and Biomedicine(2)
Source: Neelina H. Malsch_Biomedical Nanotechnology

Nanotechnology is the ability to measure, design, and manipulate at the atomic, molecular and supramolecular levels on a scale of about 1 to 100 nm in an effort to understand, create, and use material structures, devices, and systems with funda- mentally new properties and functions attributable to their small structures. All biological and man-made systems have their first levels of organization at the nanoscale (nanocrystals, nanotubes, and nanobiomotors), where their fundamental properties and functions are defined. The goal in nanotechnology may be described as the ability to assemble molecules into useful objects hierarchically integrated along several length scales and then, after use, disassemble objects into molecules. Nature already accomplishes this in living systems and in the environment.Rearranging matter on the nanoscale using “weak” molecular interactions such as van der Waals forces, H bonds, electrostatic dipoles, fluidics, and various surface forces requires low energy consumption and allows for reversible and other subse- quent changes. Such changes of usually “soft” nanostructures in a limited temper- ature range are essential for bioprocesses to take place. Research on “dry” nano- structures is now seeking systematic approaches to engineering human-made objects at nanoscale and integrating nanoscale structures into large-scale structures as nature does. While the specific approaches may be different from the slow evolutions of living systems in aqueous media, many concepts such as self-assembling, templating, interaction on surfaces of various shapes, self-repairing, and integration on multiple length scales can be used as sources of inspiration.Nanobiomedicine is a field that applies nanoscale principles and techniques to understanding and transforming inert materials and biosystems (nonliving, living or thinking) for medical purposes such as drug synthesis, brain understanding, body part replacement, visualization, and tools for medical interventions. Integration of nanotechnology with biomedicine and biology, and with information technology and cognitive science is expected to accelerate in the next decade. Convergence of nanoscale science with modern biology and medicine is a trend that should be reflected in science policy decisions.Nanobiosystem science and engineering is one of the most challenging and fastest growing components of nanotechnology. It is essential for better understand- ing of living systems and for developing new tools for medicine and solutions for health care (such as synthesis of new drugs and their targeted delivery, regenerative medicine, and neuromorphic engineering). One important challenge is understanding the processes inside cells and neural systems. Nanobiosystems are sources of inspi- ration and provide models for man-made nanosystems. Research may lead to better biocompatible materials and nanobiomaterials for industrial applications. The confluence of biology and nanoscience will contribute to unifying concepts of sci- ence, engineering, technology, medicine, and agriculture.

Nanotechnology and Biomedicine(1)

2009-06-10T00:03:00.000-07:00

Converging Technologies:
Nanotechnology and Biomedicine(1)
Source: Neelina H. Malsch_Biomedical Nanotechnology

By Mihail C. Roco
National Science FoundationChair, U.S. Nanoscale Science, Engineering and Technology (NSET)Washington, D.C.

Recent research on biosystems at the nanoscale has created one of the most dynamic interdisciplinary research and application domains for human discovery and innovation. This domain includes better understanding and treat- ment of living and thinking systems, revolutionary biotechnology processes, syn- thesis of new drugs and their targeted delivery, regenerative medicine, neuromorphic engineering, and biocompatible materials for sustainable environment. Nanobiosys- tems and biomedical research are priorities in the United States, the European Union, the United Kingdom, Australia, Japan, Switzerland, China, and other countries and regional organizations.With proper attention to ethical issues and societal needs, these converging technologies could yield tremendous improvements in human capabilities, societal outcomes, and the quality of life. The worldwide emergence of nanoscale scienceand engineering was marked by the announcement of the U.S. National Nanotech- nology Initiative (NNI) in January 2000. Its relevance to biomedicine is expected to increase rapidly in the future. The contributions made in this volume are outlined in the context of research directions for the field.

Lab on a chip

2009-06-09T20:27:00.000-07:00

Lab on a chip mimics brain chemistry

February 12th, 2008 Johns Hopkins researchers from the Whiting School of Engineering and the School of Medicine have devised a micro-scale tool – a lab on achip – designed to mimic the chemical complexities of the brain. The system should help scientists better understand how nerve cells in the brain work together to form the nervous system.
AmpliChip CYP450 Test – www.AmpliChip.us
Roche Diagnostics US Official Site FDA cleared CYP450 Test

A report on the work appears as the cover story in the February 2008 issue of the British journal Lab on a Chip. ”The chip we’ve developed will make xperiments on nerve cells more simple to conduct and to control,” says Andre Levchenko, Ph.D., associate professor of biomedical engineering at the Johns Hopkins Whiting School of Engineering and faculty affiliate of the Institute for NanoBioTechnology. Nerve cells decide which direction to grow by sensing both the chemical cues flowing through their environment as well as those attached to the surfaces that surround them. The chip, which is made of a plastic-like substance and covered with a glass lid, features a system of channels and wells that allow researchers to control the flow of specific chemical cocktails around single nerve cells.

“It is difficult to establish ideal experimental conditions to study how neurons react to growth signals because so much is happening at once that sorting out nerve cell connections is hard, but the chip, designed by experts in both brain chemistry and engineering, offers a sophisticated way to sort things out,” says Guo-li Ming,
M.D.,Ph.D., associate professor of neurology at the Johns Hopkins School of Medicine and Institute for Cell Engineering.

In experiments with their chip, the researchers put single nerve cells, or rons,onto the chip then introduced specific growth signals (in the form of hemicals).They found that the growing neurons turned and grew toward higher concentrations of certain chemical cues attached to the chip’s surfaces, as well as to signaling molecules free-flowing in solution.

When researchers subjected the neurons to conflicting signals (both surface bound and cues in solution), they found that the cells turned randomly, suggesting that cells do not choose one signal over the other. This,according to Levchenko,supports the prevailing theory that one cue can elicit different responses depending on
a cell’s surroundings. “The ability to combine several different stimuli in the chip resembles a more realistic environment that nerve cells will encounter in the living animal,” Ming says.This in turn will make future studies on the role of neuronal cells in development and regeneration more accurate and complete.

Source: Johns Hopkins Medical Institutions

Release of neurological drugs

2009-06-09T20:26:00.000-07:00

Release of neurological drugs

Reasons Why the Drug Delivery Market is Rapidly Expanding
At present, there are 30 main drug delivery products on the market. The total annual income for all of these is approximately US$33 billion with an annual growth of 15% (based on global product revenue). Two major drivers are primarily responsible for this increase in the market. First, present advances in diagnostic technology appear to be outpacing advances in new therapeutic agents. Highly detailed information from a patient is becoming available, thus promoting much more specific use of pharmaceuticals. Second, the acceptance of new drug formulations is expensive and slow, taking up to 15 years to obtain accreditation of new drug formulas with no guarantee of success.

How Drug Companies are Reacting to this Expansion
In response, some companies are trying to hurry the long clinical phase required in Western medicine. However, powerful incentives remain to investigate new techniques that can more effectively deliver or target existing drugs (Saxl, 2000). In addition, many of these new tools will have foundation in current techniques: a targeted molecule may simply add spatial or temporal resolution to an existing assay. Thus, although many potential applications are envisaged, the actual near future products are not much more than better research tools or aids to diagnosis. These are summarised in the following three tables.

More details see >> AZoNanotechnology Article

Drug delivery

2009-06-09T20:25:00.000-07:00

Drug delivery is a process, during which pharmaceutical compounds are delivered to humans or animals. Methods of delivery include several routs, such as oral, nasal, pneumonial, rectal and several others. In order to work effectively, the drug needs to work in a controlled manner, which would control the circulation of the drug in the body. Targeted delivery occurs when the drug remains active within a specified territory of the body. Targeted drug delivery is especially important in cases, when the drug needs to affect a malicious turmoil, such as in cancerous tissues.
Doctors all over the world are trying to find new methods for more effective drug development and drug delivery. One of the most successful methods developed in recent years is nanotechnology. This mechanism, which controls small-scale matter, makes it possible for drugs to permeate trough cell walls. The methods of nanotechnology play a very important role in pharma industry: health organizations manufacture more efficient drugs, released in a controlled manner in order to reach the target areas of the patients' body.
Drug development aims to find more effective drugs, which would cure or ameliorate symptoms of illness or medical condition. Drug development is required to establish the chemical properties of new compounds, their stability and chemical makeup. The process of drug development also involves the need to fit the regulatory requirements of drug licensing authorities. Pharmaceutical companies, which produce different medications, develop new methods of targeted drug delivery. Nanotechnology, developed in recent years may provide a breakthrough technique of drug delivery.
Submitted by Natalie Halimi - Content Editor in Internet Marketing Company - Inter-Dev http://www.inter-dev.co.il/en/ Drug delivery, drug development - http://www.docoop.com/

New Drug Delivery Technique

2009-06-09T20:24:00.000-07:00

New Drug Delivery Technique Avoids NeedlesBy Sarah Graham

Hypodermic needles are the stuff of nightmares for many people, but they represent a common method for administering a variety of drugs. Patients who fear a needle prick, however, may soon have an alternative, painless way to receive medication. A new technique described today in the journal BMC Medicine uses a stream of gas to help deliver drugs through the skin with what subjects describe as the sensation of a gentle stream of air.

James Weaver of the Massachusetts Institute of Technology and his colleagues developed the novel procedure, which is known as microscission. It uses minuscule inert crystals of aluminum oxide to remove the rough outer layer of skin and create tiny holes, known as microconduits and measuring less than a quarter of a millimeter in diameter, through which medication can move. A jet of flowing gas then takes the crystals and the loosened skin away. After creating four microconduits on the inner arm of volunteers, the team applied a pad soaked in the anesthetic lidocaine. Within two minutes, the drug had worked and the subjects reported no feeling in the region.

The size and depth of the microconduits is determined by holes punched in a polymer mask laid on top of the skin. The team reports that "the onset of anesthesia takes longer in microconduits deep enough to yield blood than in shallower, nonblood producing microconduits." But deep microconduits do have some advantages. Patients suffering from diabetes, for example, often have to jab a finger to test their blood sugar; microscission could represent a less painful alternative, the team suggests.

Source>http://www.scientificamerican.com/

Nanocontainers Deliver Drugs

2009-06-09T20:22:00.000-07:00

Nanocontainers Deliver Drugs Directly to Cells
By Sarah Graham
April 28, 2003

One challenge to effective drug treatment is getting the medication to exactly the right place. To that end, researchers have been investigating myriad new methods to deliver pharmaceuticals. Findings published in the current issue of the journal Science indicate that tiny nanocontainers composed of polymers may one day distribute drugs to specific spots within individual cells.
Radoslav Savic and his colleagues at McGill University tested the properties of tiny units built out of two types of polymers. The two compounds self-assemble into a spherical shape known as a micelle. One compound, which is hydrophobic (water fearing), aligns facing inwards and the other, which is hydrophilic (water loving), faces outwards. Drugs can then be loaded inside the tiny molecular globs, which measure 20 to 45 nanometers in diameter. The researchers used fluorescent labeling to track the micelles' journeys (see image). They found that the tiny containers could pass through the wall of a rat cell, but did not enter the cell's nucleus. The micelles did, however, penetrate some cell parts, such as mitochondria and the Golgi apparatus, which are important targets for drug delivery.
The scientists also determined that the micelles are very efficient at delivering their hydrophobic drug cargo once inside a cell. This property could mean that doctors may one day be able to administer smaller doses of toxic medications. "These micelles may thus be worth exploring for their potential to selectively deliver drugs to specified subcellular targets," the authors note. In an accompanying commentary, Jeffrey A. Hubbell of the University of Zurich cautions that much work remains to be done, "yet, multifunctional polymer micelles have already come a long way to reaching these ends."

Source >http://www.scientificamerican.com/article.cfm?id=nanocontainers-deliver-dr

Nanoparticles Home in on Brain Cancer

2009-06-09T20:21:00.000-07:00

Nanoparticles Home in on Brain Cancer
By Nikhil Swaminathan
November 17, 2006

Call them laser-guided smart bombs for brain tumors. Researchers at the University of Michigan announced the testing of a drug delivery system that involves drug-toting nanoparticles and a guiding peptide to target cancerous cells in the brain. Their study finds that via this method more of the drug can be delivered to a tumor's general vicinity. They report their findings in the November 15 issue of Clinical Cancer Research.
The researchers used a pharmaceutical called Photofrin, which is photodynamic, meaning it is activated by a laser after it has entered the bloodstream. As its primary side effect, the drug renders patients photosensitive, and they must remain out of bright sunlight and even unshaded lamps for up to 30 days after receiving treatment. Despite this major drawback, Photofrin is used in the treatment of esophageal, bladder and skin cancers. But their novel delivery system, which relies on the intravenous delivery of 40-nanometer-wide particles to carry the drug, may actually avoid much of the photosensitivity, because less Photofrin circulates in the bloodstream thanks to a peptide called F3. A sequence of 31 amino acids broken off of the protein HMGN2 (high mobility group protein 2), F3 has the ability to penetrate cell membranes. "This peptide acts as a "zip code" in that it enables the binding of the nanoparticles only to blood vessels within the tumor and not normal blood vessels," says Alnawaz Rehemtulla, a radiologist and environmental health scientist who co-authored the study. F3 can detect the expression of a protein called nucleolin, which is a marker on the surface of tumor cells.
Another problem the researchers avoided was having to deliver their medicine in such a way that it could cross the blood-brain barrier, which keeps many substances from entering the brain from the bloodstream. Typical chemotherapies must penetrate this shield to treat tumors. In this case, however, the nontoxic polyacrylamide particles didn't have to cross over via the bloodstream. "The nanoparticles do not need to cross the blood-brain barrier as they were specifically designed to target the blood vessel cells within the tumor," explains radiologist Brian Ross, one of the study's authors. "The treatment should be thought of as an antivascular treatment thereby shutting off the tumor blood flow resulting in the death of the tumor cells through starvation of oxygen and energy sources."
To test the delivery method, researchers divided 34 rats--all who received injections of cancerous cells into their brains--into different groups. Those that received no treatment or got only the laser fared poorly, dying on average within 8.5 days. Those that got Photofrin either intravenously or encapsulated in nanoparticles had a median survival time of 13 days. The group that got F3 with the Photofrin-carrying nanoparticles came through the best: they lived for, on average, 33 days; three of the five in this grouping lived for 60 days, and two of those three appeared tumor-free after six months. By using iron oxide as a contrast agent--to more easily detect where the nanoparticles ended up via MRI--the group determined that twice as much drug with the F3 peptide attached reached the tumor site--10 percent of the total amount administered--compared with when nontargeted nanoparticles were injected.
Ross says that based on the success of the study, the team is investigating if this delivery technology will work for nonphotodynamic therapies. Rehemtulla adds that if other FDA-approved chemotherapeutic agents reach their targets as successfully as Photofrin did, "then we will have developed a way to make cancer drugs more 'tumor-specific,' because they will only get into tumor vasculature and not normal vasculature. This will spare patients from normal tissue toxicity that is commonly associated with almost all chemotherapy."

Source>http://www.scientificamerican.com/article.cfm?id=nanoparticles-home-in-on

Ultrasonic Nanotechnology

2009-06-09T11:40:00.000-07:00

Revolutionary Ultrasonic Nanotechnology
May Allow Scientists To See Inside Patient’s Individual Cells
ScienceDaily (June 3, 2009)

—> Revolutionary ultrasonic nanotechnology that could allow scientists to see inside a patient’s individual cells to help diagnose serious illnesses is being developed by researchers at The University of Nottingham.

The technology would be tiny enough to allow scientists to see inside and image individual cells in the human body, which would further our understanding of the structure and function of cells and could help to detect abnormalities to diagnose serious illnesses such as some cancers.
The work by the Ultrasonics Group in the Division of Electrical Systems and Optics has been deemed so potentially innovative it has recently been awarded a £850,000 five-year Platform Grant by the Engineering and Physical Sciences Research Council (EPSRC).
Ultrasound refers to sound waves that are at a frequency too high to be detected by the human ear, typically 20 kHz and above. Medical ultrasound uses an electrical transducer the size of a matchbox to produce sound waves at much higher frequencies, typically around 100-1000 times higher to probe bodies.
The Nottingham researchers are aiming to produce a miniaturised version of this technology, with transducers so tiny that you could fit 500 across the width of one human hair which would produce sound waves at frequencies a thousand times higher again, in the GHz range.
Dr Matt Clark of the Ultrasonics Group, said: “By examining the mechanical properties inside a cell there is a huge amount that we can learn about its structure and the way it functions. But it’s very much a leap into the unknown as this has never been achieved before.
“One of the reasons for this is that it presents an enormous technical challenge. To produce nano-ultrasonics you have to produce a nano-transducers, which essentially means taking a device that is currently the size of a matchbox and scaling it down to the nanoscale. How do you attach a wire to something so small?
“Our answer to some of these challenges is to create a device that works optically — using pulses of laser light to produce ultrasound rather than an electrical current. This allows us to talk to these tiny devices.”
The new technology may also allow scientists to see objects even smaller than optical microscopes and be so sensitive they may be able to measure single molecules.
In addition to medical applications, the new technology would have important uses as a testing facility for industry to assess the integrity and quality of materials and to detect tiny defects which could have an impact on performance or safety.
Ultrasonics is currently used in applications such as testing landing gear components in the aero industry for cracks and damage which may not be immediately visible or may develop with use.
The group is also looking at developing new inspection techniques for inspecting engineering metamaterials — advanced composites that are currently impossible to inspect with ultrasound. These materials offer huge performance advantages allowing radical new engineering but can't be widely used because of the difficulty of inspection.
Dr Clark added: “We are also applying our technology to nanoengineering because we have to match the enormous growth in nanotechnology with techniques to inspect the nanoworld. As products and their components become ever tinier, the testing facilities for those also need to be scaled down accordingly.
In NEMS (nanoelectromechanical) and MEMS (microelectromechanical) based machines there is an increasing demand for testing facilities which offer the same capabilities as those for real-world sized devices.

Source:University of Nottingham (2009, June 3).
Revolutionary Ultrasonic Nanotechnology
May Allow Scientists To See Inside Patient’s Individual Cells.
ScienceDaily. Retrieved June 11, 2009,
from >http://www.sciencedaily.com /releases/2009/06/090602134943.htm

Capsules Encapsulated

2009-06-09T11:30:00.000-07:00

Drug Deliver With Nanotechnology:
Capsules Encapsulated
ScienceDaily (May 20, 2009)

—> When cells cannot carry out the tasks required of them by our bodies, the result is disease. Nanobiotechnology researchers are looking for ways to allow synthetic systems take over simple cellular activities when they are absent from the cell. This requires transport systems that can encapsulate medications and other substances and release them in a controlled fashion at the right moment.

The transporter must be able to interact with the surroundings in order to receive the signal to unload its cargo. A team led by Frank Caruso at the University of Melbourne has now developed a microcontainer that can hold thousands of individual "carrier units"—a "capsosome". These are polymer capsules in which liposomes have been embedded to form subcompartments.
Currently, the primary type of nanotransporter used for drugs is the capsule: Polymer capsules form stable containers that are semipermeable, which allows for communication with the surrounding medium. However, these are not suitable for the transport of small molecules because they can escape. Liposomes are good at protecting small drug molecules; however, they are often unstable and impermeable to substances from the environment. The Australian researchers have now combined the advantages of both systems in their capsosomes.
Capsosomes are produced by several steps. First, a layer of polymer is deposited onto small silica spheres. This polymer contains building blocks modified with cholesterol. Liposomes that have been loaded with an enzyme can be securely anchored to the cholesterol units and thus attached to the polymer film. Subsequently, more polymer layers are added and then cross-linked by disulfide bridges into a gel by means of a specially developed, very gentle cross-linking reaction. In the final step, the silica core is etched away without damaging the sensitive cargo.
Experiments with an enzyme as model cargo demonstrated that the liposomes remain intact and the cargo does not escape. Addition of a detergent releases the enzyme in a functional state. By means of the enzymatic reaction, which causes a color change of the solution, it was possible to determine the number of liposome compartments to be about 8000 per polymer capsule.
"Because the capsosomes are biodegradable and nontoxic", says Brigitte Staedler, a senior researcher in the group, "they would also be suitable for use as resorbable synthetic cell organelles and for the transport of drugs." In addition, the scientists are planning to encapsulate liposomes filled with different enzymes together and to equip them with specific "receivers" which would allow the individual cargo to be released in a targeted fashion. This would make it possible to use enzymatic reaction cascades for catalytic reaction processes.

Source:Wiley-Blackwell (2009, May 20).
Drug Deliver With Nanotechnology:
Capsules Encapsulated.
ScienceDaily. Retrieved June 11, 2009,
from> http://www.sciencedaily.com/ /releases/2009/05/090519134717.htm

Drug Delivery Systems

2009-06-09T00:12:00.000-07:00

Drug Delivery SystemsMarkets and Applications for Nanotechnology Derived Drug Delivery SystemsBackgroundThe most promising aspect of pharmaceuticals and medicine as it relates to nanotechnology is currently drug delivery. In the words of LaVan and Langer: ‘It is likely that the pharmaceutical industry will transition from a paradigm of drug discovery by screening compounds to the purposeful engineering of targeted molecules.’
Reasons Why the Drug Delivery Market is Rapidly Expanding At present, there are 30 main drug delivery products on the market. The total annual income for all of these is approximately US$33 billion with an annual growth of 15% (based on global product revenue). Two major drivers are primarily responsible for this increase in the market. First, present advances in diagnostic technology appear to be outpacing advances in new therapeutic agents. Highly detailed information from a patient is becoming available, thus promoting much more specific use of pharmaceuticals. Second, the acceptance of new drug formulations is expensive and slow, taking up to 15 years to obtain accreditation of new drug formulas with no guarantee of success.
How Drug Companies are Reacting to this Expansion In response, some companies are trying to hurry the long clinical phase required in Western medicine. However, powerful incentives remain to investigate new techniques that can more effectively deliver or target existing drugs (Saxl, 2000). In addition, many of these new tools will have foundation in current techniques: a targeted molecule may simply add spatial or temporal resolution to an existing assay. Thus, although many potential applications are envisaged, the actual near future products are not much more than better research tools or aids to diagnosis. These are summarised in the following three tables.
More details see >> AZoNanotechnology Article

3.MICRO AND NANO DRUG DELIVERY SYSTEMS(cont.)

2009-06-08T23:59:00.000-07:00

3.MICRO AND NANO DRUG DELIVERY SYSTEMS(cont.)
3.4.Dendrimers
Dendrimers are small molecules which have a core and a series of branches symmetrically formed around the core resulting in a monodisperse, symmetrical macromolecule. They can be synthesized either starting from the core molecules and going out to the periphery by connecting the branch groups or by forming the branches first and then collecting all around the core. Functionality of the branching units is generally 2 or 3, which makes the layer of branching units doubles or triples. The interior cavity is very suitable for the entrapment of the drugs and their unique properties such as high degree of branching, multivalency, globular architecture and well-defined molecular weight, make dendrimers promising new carriers for drug delivery. Their nanometer size, ease of preparation and functionalization, and their ability to display multiple copies of surface groups for biological reorganization processes increase their attraction in biomedical applications.Interaction of dendrimer macromolecules with the molecular environment is predominantly controlled by their terminal groups. By modifying their termini, the interior of a dendrimer may be made hydrophilic while its exterior surface is hydrophobic, or vice versa. Drug molecules can be loaded both in the interior of the dendrimers as well as attached to the surface groups. Water-soluble dendrimers are capable of binding and solubilizing small molecules and can be used as coating agents to protect or deliver drugs to specific sites in the body or as time-release vehicles for transporting biologically active agents. In the last decades, research has increased on the design and synthesis of biocompatible dendrimers and their application to many areas of bioscience including drug delivery, immunology and the development of vaccines, antimicrobials and antivirals gained great attantion.A series of lipidic peptide dendrimers based on lysine with 16 surface alkyl (C12 ) chains has been synthesised by Florence et al (2000). A fourth generation dendrimer with a diameter of 2.5 nm was studied for its absorption at different organs after

3.MICRO AND NANO DRUG DELIVERY SYSTEMS(cont.)

2009-06-08T23:56:00.000-07:00

3.MICRO AND NANO DRUG DELIVERY SYSTEMS(cont.)
3.3.Ceramic Nanoparticles

Use of ceramics in medicine is especially significant in dental and orthopedic applications as strengthening materials for the hard tissue implants. Hydroxyapatite (HA) is a ceramic naturally existing in the bone structure and therefore its use in the hip or knee prosthesis can reduce the risk of rejection and stimulate the production of osteoblasts which are the cells responsible for the growth of the bone matrix.Ceramic particles effectively protect the doped molecules (enzymes, drugs, etc) against denaturation induced by external pH and temperature. In addition, their surfaces can be easily modified with different functional groups. They can be conjugated to a variety of monoclonal antibodies or ligands for targeting purposes in vivo. Ceramic particles with entrapped biomolecules have a great potential in delivery of drugs. Such particles, including silica, alumina, titania, etc, are known for their compatibility with biological systems. They have several advantages such as the ease of preparation with the desired size, shape and porosity under ambient conditions, high stability such as no swelling or change in shape in environmental conditions.McQuire et al (2005) synthesized hydroxyapatite sponges by using aminoacid coated HA nanoparticles dispersed within a viscous polysaccharide (dextran sulfate) matrix and examined the use of these materials for the viability and proliferation of human bone marrow stromal cells in order to search possibility for cartilage or soft tissue engineering. Rusu et al (2005) studied size-controlled hydroxyap- atite nanoparticles prepared in aqueous media in a chitosan matrix from soluble precursors salts bone for the purpose of tissue engineering applications. Serbetci et al (2000, 2002, 2004) prepared acrylic bone cements with addition of HA microparticles. They examined the effect of HA addition on the properties of the cement. They reported enhancement of mechanical, thermal and biological properties depending on the added amount of HA.Christel and co-workers (1984) implanted calcium phosphate bioglass ceramics in the tibiae of rabbits to study the interface of bioceramics. It was reported that hydroxyapatite surface give rise to a closer contact with new bone than calcium phosphate glass ceramics. Lin and colleagues (1996) implanted bioglass discs into the condyle area of rabbits. The failure load, when an implant detached from the bone or when the bone itself broke, was measured by a push-out test and compared with sintered hydroxyapatite bioceramic. Vogel and coworkers (2001) implanted bioglass particles in the distal femoral epiphysis of rabbits and examined bone formation at the implant site. They discussed the parameters (implantation model, particle size and surface-area-to-volume ratio) as possible parameters determining bone regeneration. Recently Amaral and colleagues (2002) studied wettability and surface charge properties of Si3 N4 –bioglass biocomposites. They determined that the examined bioglass had comparatively higher hydrophilic character and surface tension value than the most common bioceramics. The presence of very high negative zeta potential at neutral pH influenced albumin adsorption. They also studied mechanisms in terms of entropy and enthalpy gains from conformational unfolding and cation coadsorption (Amaral et al 2002).Zeng and co-workers (2002) prepared Al2 O3 –A/W bioglass coating through tape casting process by selecting low melting point A/W bioglass to decrease the Al2 O3 sintering temperature and modify the bioactivity of implant. On the other hand, Xin and colleagues (2005) investigated the formation of calcium phosphate (Ca-P) on various bioceramic surfaces in simulated body fluid (SBF) and in rabbit muscle. The bioceramics were sintered porous solids, including bioglass, glass-ceramics, hydroxyapatite, -tricalcium phosphate and -tricalcium phosphate. They compared the ability of inducing Ca-P formation and obtained similar results in SBF but observed considerable variations in vivo.

Source:
Nanomaterials and Nanosystems for Biomedical Applications
NESRIN HASIRCI
Middle East Technical University, Faculty of Arts and Sciences, Department of Chemistry, Ankara 06531, Turkey

3.MICRO AND NANO DRUG DELIVERY SYSTEMS(cont.)

2009-06-08T23:50:00.000-07:00

3.MICRO AND NANO SYSTEMS (cont)

3.2.Liposomes
Liposomes are small spherical vesicles in which one or more aqeous compart- ments are completely enclosed by molecules that have hydrophilic and hydrophobic functionality such as phospholipids and cholesterol. Properties of liposomes vary substantially with composition, size, surface charge and method of preparation. They can be formed as single lipid bilayer or in multiple bilayers. Liposomes containing one bilayer membrane are termed small unilamellar vesicles (SUV) or large unilamellar vesicles (LUV) based on their size ranges (Mozafari and Sahin2005). If more than one bilayer is present then they are called multilamellar vesicles (MLV). Liposomes are commonly used as model cells or carriers for various bioactive agents including drugs, vaccines, cosmetics and nutraceuticals.The introduction of positively or negatively charged lipids provides the liposomes a surface charge. Drugs associated with liposomes have markedly altered pharma- cokinetic properties compared to free drugs in solution. Liposomes are also effective in reducing systemic toxicity and preventing early degradation of the encapsu- lated drug after introduction to the body. They can be covered with polymers such as polyethylene glycol (PEG) – in which case they are called pegylated or stealth liposomes – and exhibit prolonged half-life in blood circulation (Mozafari et al 2005). Furthermore, liposomes can be conjugated to antibodies or ligands to enhance target-specific drug therapy. Visser et al (2005) studied targeting of pegylated liposomes loaded with horse radish peroxidase (HRP) and tagged with transferrin to the blood-brain barrier in vitro. They have shown effective targetting of liposomes loaded with protein or peptide drugs to the brain capillary endothelialcells and suggested that the system is an attractive approach for drug delivery to brain. Lopez-Pinto and coworkers (2005) examined the dermal delivery of a lipophilic drug, minoxidil, from ethosomes versus classic liposomes by appliying the vesicles non-occlusively on rat skin. They studied the permeation pattern, depth into the skin and the main permeation pathway of different liposomal systems. Ozden and Hasirci (1991) prepared small unilamellar vesicles composed of phosphatidyl- choline, dicetyl phosphate and cholesterol and entrapped glucose oxidase in them. They obtained loading efficiency as one protein per liposomal vesicle.Liposomes containing the expression vector pRSVneo coding for neomycin phosphotransferase–II were studied by Leibiger et al (1991) for a gene transfer into rat liver cells in vivo. After intravenous application of liposomes to male Wistar-rats, nonintegrated vector DNA was detected by blot-hybridisation in isolated nuclei of hepatocytes. Cirli and Hasirci (2004) prepared calcein encapsulated reverse phase evaporation vesicles carrying photoactive destabilization agent suprofen in the lipid bilayer. They investigated the effect of UV photoactivation of liposomal membrane- incorporated suprofen on the destabilization of the liposome bilayer and the release of encapsulated calcein as a model active agent.Liposomes are also studied as carriers for cells, genes or DNA fragments. Ito et al (2004) studied the effect of magnetite cationic liposomes which have positive surface charge to enrich and proliferate Mesenchymal stem cells (MSCs) in vitro. Kunisawa et al (2005) established a protocol for the encapsulation of nanoparticles in liposomes, which were further fused with ultra violet-inactivated Sendai virus to compose fusogenic liposomes and observed that fusogenic liposome demonstrated a high ability to deliver nanoparticles containing DNA into cytoplasm. Ito et al (2005) investigated whether coating the culture surface with RGD (Arg–Gly–Asp) conju- gated magnetite cationic liposomes (RGD-MCLs) was able to facilitate cell growth, cell sheet construction and cell sheet harvest using magnetic force without enzymatic treatment. They reported that cells adhered to the RGD-MCLs coated bottom of the culture surface, spreaded and proliferated to confluency. Detachment and harvesting of the cells did not need enzymatic process. Fuentes et al (2003) studied the adjuvan- ticity of two gamma inulin/liposomes/Vitamin E combinations in the mouse, in contraceptive vaccines by using sperm protein extracts or a synthetic HE2 peptide (Human Epididymis gene product; residues 15–28) as antigen. They showed that the gamma inulin/liposomes/Vitamin E combination, with sperm protein extracts, was better than Freund’s adjuvant. When the synthetic HE2 peptide was used as antigen, the gamma inulin/liposomes/Vitamin E combination was less effective than Freund’s adjuvant.Vierling et al (2001) published a review on fluorinated liposomes made from highly fluorinated double-chain phospho- or glyco-lipids as well as fluorinated lipoplexes, e.g. complexes made from highly fluorinated polycationic liposper- mines and a gene. The properties of the fluorinated lipoplexes including stability and in vitro cell transfection in the presence of serum or bile were reported. El Maghraby et al (2004) showed that incorporation of activators (surfactants) into liposomes improved estradiol vesicular skin delivery. They examined the interactions of additives with dipalmitoylphosphatidylcholine (DPPC) membranes by using high sensitivity differential scanning calorimetry. Lopes and colleagues (2004) investigated the encapsulation of acid (AD) and sodium diclofenac (SD) in small unilamellar liposomes (SUV) prepared by sonication from multilamellar liposomes containing soya phosphatidylcholine and diclofenac at various propor- tions. The interactions of the drug with the bilayers were examined. They proposed a schematic model for interaction of SD with phosphatidylcholine of the liposomes in which the diclofenac anion interacts with the ammonium group of the phospho- lipid and the dichlorophenyl ring occupies a more internal site of bilayer near phosphate group. Simard et al (2005) prepared multilamellar vesicles by shearing a lamellar phase of lipids and surfactants. They reported formation of vesicles with mean diameter of less than 300 nm in which hydrophilic drugs can be loaded with high yield. They coated the vesicles with PEG and loaded them with 1-d-arabinofuranosylcytosine. Following injection of the vesicles intravenously to rats they observed that the surface-modified liposomes exhibited longer circulation times compared to uncoated liposomes.Koynova and MacDonald (2005) examined the lipid exchange between model lipid systems, including vesicles of the cationic lipoids ethyl dimyristoyl phosphatidylcholine, ethyl dipalmitoyl phosphatidylcholine or their complexes with DNA, and the zwitterionic lipids by using differential scanning calorimetry. They observed that, exchange via lipid monomers was considerably more facile for the cationic ethylphosphatidylcholines than for zwitterionic phosphatidylcholines and for the cationic liposomes. The presence of serum in the dispersing medium strongly promoted lipid transfer between cationic vesicles while almost no effect was reported for zwitterionic liposomes. This phenomenon was proposed as an important point for the application of cationic liposomes as nonviral gene delivery. Foco et al (2005) studied the delivery of sodium ascorbyl phosphate (SAP), an effective oxygen species scavenger to prevent the degenerative effects of UV radiation on skin. SAP was encapsulated into liposomes to improve its penetration through the stratum corneum into the deeper layers of the skin. They prepared two types of multilamellar vesicles, one from non-hydrogenated and the other from hydrogenated soybean lecithin, together with cholesterol. Sinico et al (2005) studied transdermal delivery of tretinoin and examined the influence of liposome composition, size, lamellarity and charge on transdermal delivery. They studied positively or negatively charged liposomes of different types, i.e. multilamellar vesicles (MLV) or unilamellar vesicles (ULV), prepared from hydrogenated soy phosphatidylcholine (Phospholipon® 90H) or non-hydrogenated soy phosphatidyl- choline (Phospholipon® 90) and cholesterol, in combination with stearylamine or dicetylphosphate. It was reported that negatively charged liposomes strongly improved newborn pig skin hydration and tretinoin retention.Arcon et al (2004) encapsulated an anticancer agent, cisplatin, in sterically stabilized liposomes and studied the systems with extended X-ray absorption fine structure (EXAFS) method, and concluded that the liposome-encapsulated drug is chemically stable and does not hydrolyze. Sapra and Allen (2003) published a review article about the ligand-targeted liposomes (LTLs) for the delivery of anticancer drugs. In this article, new approaches used in the design and optimization of LTLs was discussed and the advantages and potential problems associated with their therapeutic applications were described.

Source:
Nanomaterials and Nanosystems for Biomedical Applications
NESRIN HASIRCI
Middle East Technical University, Faculty of Arts and Sciences, Department of Chemistry, Ankara 06531, Turkey

3.MICRO AND NANO DRUG DELIVERY SYSTEMS(cont.)

2009-06-08T23:41:00.000-07:00

3.MICRO AND NANO DRUG DELIVERY SYSTEMS(cont.)
3.1.Micelles

Micelles are ideal bioactive nanocarriers, especially for water insoluble agents. Many amphiphilic block copolymers can be used for this purpose. Polymers can self-associate to form spherical micelles in aqueous solution by keeping hydrophilic ends as the outer shell and the hydrophobic ends as the core. Hydrophobic drugs can be entrapped in the core during micelle formation process. Polymeric micelles have good thermodynamic stability in
physiological solutions, as indicated by their low critical micellar concentration, which makes them stable and prevents their rapid dissociation in vivo. The sizes of micelles are generally less than 100 nm in diameter. This provides them with long-term circulation in blood stream and enhanced endothelial cell ermeability in the vicinity of solid tumors by passive diffusion. If site-specific ligands or antibodies are conjugated to the surface of the micelles, the drug targeted delivery potential of polymeric micelles can be enhanced.Kataoka et al (2000) studied the effective targeting of cytotoxic agents to solid tumors by polymeric micelles. They conjugated doxorubicin to poly(ethylene glycol)-poly( , -aspartic acid) block copolymers and showed that these micelles achieved prolonged circulation in the blood compartment and accumulated more in
the solid tumor, leading to complete tumor regression against mouse C26 tumor. Rapoport (1999) studied stabilization and activation of Pluronic micelles for tumor- targeted drug delivery. Aliabadi et al (2005a) examined
the potential of polymeric micelles to modify the pharmacokinetics and tissue distribution of cyclosporine A (CsA). Their results demonstrated that PEO-b-PCL micelles can effectively solubilize CsA confining CsA to the blood circulation and restricting its access to tissues such as kidney, perhaps limiting the onset of toxicity. They also investigated micelles of methoxy poly (ethylene oxide)–b–poly ( –caprolactone) (PEO–b–PCL) as alternative vehicles for the solubilization and delivery of Cyclosporine A (Aliabadi et al 2005b). They concluded that these nanoscopic PEO–b–PCL micelles have high potential as drug carriers for efficient solubilization and controlled delivery of CsA. Prompruk et al (2005) synthesized a functionalized copolymer with three polymeric components,poly (ethylene glycol)–block–poly (aspartic acid–stat- phenylalanine) and investigated its potential to form micelles via ionic interactions with diminazene aceturate as a model water-soluble drug.Wasylewska et al (2004) entrapped human prostatic acid phosphatase (PAP)entrapped in AOT–isooctane–water reverse micelles and studied the kinetics of1–naphthyl phosphate and phenyl phosphate hydrolysis, catalyzed by PAP. Wang et al (2004) prepared polymeric micelles from poly (ethylene glycol)–distearoyl phosphoethanolamine conjugates (PEG–DSPE) loaded with
Vitamin K3 (VK3) and with 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU). These micelles were stable for 6 months during storage at 4°C and no change in their size or release of the incorporated drugs were observed. They showed that these loaded micelles resulted in synergistic anticancer effects against both murine and human cancer cells in vitro. Kang et al (2004) prepared A-B-A triblock and star-block amphiphilic copolymers such as poly (N–(2–hydroxypropyl) methacrylamide)–block–poly (D,L–lactide)–block–poly (N–(2–hydroxy propyl) methacrylamide), poly (N–vinyl-2–pyrrolidone)–block–poly (D,L–lactide)–block–poly (N–vinyl–2–pyrrolidone), star–poly (D,L–lactide)–block–poly
(N–(2–hydroxypropyl) methacryl amide) and star–poly (D,L–lactide)–block–poly (N–vinylpyrrolidone). They reported that all copolymers self-assembled in aqueous solution to form supramolecular aggregates of 20–180 nm in size. The prepared triblock copolymer micelles were examined as carriers for two drugs, indomethacin and paclitaxel, which are poorly water- soluble. Carrillo and Kane (2004) studied the formation and characterization of self– assembled nanoparticles of controlled sizes based on amphiphilic block copolymers synthesized by ring-opening metathesis polymerization. They showed that the monomer undergoes living polymerization and forms assembled nanoparticles of controlled size. The obtained micelles were fairly monodisperse with dimensions of 30–80 nm depending on the composition of the block polymer.Synthetic copolymers containing phosphorylcholine structure can also be used in the formation of micelles. Phosphorylcholine-based polymers mimic the surface of natural phospholipid membrane bilayers and therefore
demonstrate good biocom- patability. Salvage et al (2005) copolymerised 2-methacryloyloxyethyl phospho- rylcholine (MPC) with two pH responsive comonomers, 2–(diethylamino) ethyl methacrylate (DEA) and 2–
(diisopropyl amino) ethyl methacrylate (DPA), in order to develop pH responsive biocompatible drug delivery vehicles. Koo et al (2005) studied sterically stabilized micelles (SSM) and evaluated camptothecin- containing SSM CPT–SSM) as a new nanomedicine for parenteral administration where camptothecin is a well-established topoisomerase I inhibitor against a broad spectrum of cancers. Konno et al (2001) have shown that 2-ethacryloyloxyethyl phosphorylcholine (MPC) polymer immobilized on poly (l–lactic acid) nanopar- ticles effectively suppressed any unfavourable interactions with biocomponents and improved the blood compatibility of the nanoparticles. It has been suggested that the nanoparticles immobilized with the MPC polymer have the potential use as long–circulating micelles and are good candidates for carrying drugs and diagnostic reagents which can come in contact with blood components. Nishiyama et al (2005) published a review article about
construction and characteristic behaviors of intracellular environment-sensitive micelles that selectively exert drug activity and gene expression in live cells. Xiong et al (2005) grafted poly (lactic acid) to both ends of
Pluronic F87 block copolymer (PEO–PPO–PEO) to obtain amphiphilic P(LA-b-EO-b-PO-b-EO-b-LA) block copolymers. Various types of particles consisting of small micelles were obtained due to the complex structure of the copolymers and a constant initial release rates were observed for procain hydrochloride. Sot and coworkers (2005) investigated the behaviour of N–hexadecanoyl sphingosine (Cer16), N–hexanoylsphingosine (Cer6) and N–acetyl sphingosine (Cer2) ceramides in aqueous media and in lipid-water systems. Cer16 behaved as an insoluble non-swelling amphiphile while both Cer6 and Cer2 behaved as soluble amphiphiles in aqueous solutions. They observed micelle formations for Cer6 and Cer2 at high concentrations as well as phospholipid monolayer formation when the air-water interface is occupied by a phospholipid.Responsivity can be added to micelles by combining pH or temperature sensitive functional groups into the structures. Cammas et al (1997) prepared thermo- responsive polymeric micelles from amphiphilic block copolymers composed of N–isopropylacrylamide as a thermo-responsive outer shell and styrene as hydrophobic inner core. Leroux et al (2001) studied N–isopropylacrylamide bearing pH-responsive polymeric micelles and
liposomes as a delivery system for the photosensitizer aluminum chloride phthalocyanine (AlClPc), which was evaluated in photodynamic therapy. pH-responsive polymeric micelles loaded with AlClPc were found to exhibit
increased cytotoxicity against EMT-6 mouse mammary cells in vitro. Liu et al (2003) synthesized cholesteryl end-capped thermally responsive amphiphilic polymers with two different hydrophobic/hydrophilic chain-length
ratios from the hydroxyl-terminated random poly (N–isopropylacrylamide–co–N, N–dimethylacrylamide) and cholesteryl chloroformate. The micellar nanoparticles prepared from the amphiphilic polymers demonstrated
temperature sensitivity. It was suggested that these nanoparticles would make an interesting drug delivery system. Nostrum (2004) reviewed the results of photosensitizers for photodynamic therapy including drug
loading, biodistribution studies, and therapeutic efficiency and concluded that pH-sensitive micelles appeared to be promising candidates for photosensitizer delivery.

Source:
Nanomaterials and Nanosystems for Biomedical Applications
NESRIN HASIRCI
Middle East Technical University, Faculty of Arts and Sciences, Department of Chemistry, Ankara 06531, Turkey

MICRO AND NANO SYSTEMS(4)

2009-06-08T23:35:00.000-07:00

3.MICRO AND NANO DRUG DELIVERY SYSTEMS

One of the most attractive areas of micro and nano research is drug delivery. This includes the design of micro and nano carriers, synthesis of nanomedicines and production of nanosystems that are able to deliver therapeutic drugs to the specific organs or tissues in the body for appropriate periods. For drug delivery vehicles it is very important that these systems have good blood and biocompatibility properties. They themselves or the degradation products should not have any toxic, allergic or inflammatory effects. The systems should also protect the activity of the drugs and improve their transport through the biological barriers. If some specific functionality is added on the system, it would also be possible to deliver the drug to the target site where the system is
stimulated by an appropriate signal.In the design and formulation of delivery systems, the key parameters are the size of the device, entrapment method, stability of drug, degradation parameters of the matrix and release kinetics of drugs. Nanosystems have many advantages over the micro systems such as circulation in blood stream for longer periods without being recognized by macrophages, ease of penetration into tissues through capillaries and biological membranes, ability to be taken up by cells easily, demonstrating high therapeutic activity at the target site, and sustaining the effect at the desired area over a period of days or even weeks. In the last decades, numerous publications came up to describe the design of delivery systems with novel preparation methods, physicochemical properties, and bioactivities.Drug delivery is an interdisciplinary area of research that aims to make the administration of complex drugs feasible. Over the recent years there has been an increasing interest in developing new delivery systems by collaborative research of basic scientists, engineers, pharmacologists, physicians and other health related scientists. The main purpose is to deliver the drug to the desired tissue in the biological system so that it would achieve higher activity for prolonged period at the site without risk of side effects. Micro and nano drug delivery systems are developed for these purposes especially to target the drugs to a specific area or organ in a more stable and reproducible controlled way.Entrapment or conjugation of a drug to a polymeric system may protect the drug from inactivation and help to store its activity for prolonged durations, decrease its toxicity, as well as may achieve administration flexibility.
Various delivery systems, such as emulsions, liposomes, micro and anoparticles, are of major interest in the field of biomedicine and pharmaceutics. Generally biodegradable and bioabsorbable matrices are preferred so that they
would degrade inside the body by hydrolysis or by enzymatic reactions and does not require a surgical operation for removal.Targeted delivery can be achieved by either active or passive targeting. Active targeting of a therapeutic agent is
achieved by conjugating the therapeutic agent or the carrier system to a tissue or cell-specific ligand. Passive targeting is achieved by coupling the therapeutic agent to a macromolecule that passively reaches the target organ. Muvaffak et al (2002, 2004a, 2004b, 2005) prepared anticancer drug- containing gelatin microspheres and conjugated antibodies on the surfaces of these biodegradable microspheres. It was reported that the systems prepared in this way demonstrated specific activity towards its antigen. Monsigny et al (1994) reviewed the main properties of neoglycoproteins and glycosylated polymers which have been developed to study the properties of endogenous lectins and to carry drugs which can form specific ligands with cell surface receptors. The glycocon- jugates have been successfully used to carry biological response modifiers such as N-acetylmuramyldipeptide which is hundreds of times more efficient in rendering macrophages tumoricidal when it is bound to this type of
carriers. Complexes of polycationic glycosylated polymers with plasmid DNA molecules are also very efficient in transfecting cells in a sugar-dependent manner.Bioactive agents can be incorporated in micro and nano systems or in systems which have microporous structures. Local delivery of drugs or growth factors which are embedded in microporous gelatin structures was
reported by Ulubayram and coworkers (2001, 2002). They examined release kinetics of bovine serum albumin proteins from gelatin matrices (Ulubayram et al 2002) and also reported fast and proper healing of full skin defects on rabbits with application of gelatin sponges loaded with epidermal growth factor (EGF) (Ulubayram et al 2001). EGF was added in gelatin microspheres which were crosslinked with various amounts of crosslinkers (Ulubayram et al 2001, 2002). Similar systems were studied by Sakallioglu and colleagues (2002, 2004) and
positive effects of low-dose EGF loaded gelatin microspheres in colonic anastomosis were reported. Uguralp et al (2004) also reported positive effects of sustained and local administration of EGF incorporated to biodegradable
membranes on the healing of bilateral testicular tissue after torsion. Guler et al (2004) examined the effects of locally applied fibroblast containing microporous gelatin sponges on the testicular morphology and blood flow in
rats.There are a large number of studies investigating the drug releasing responses to various stimuli such as pH, temperature, electric field, ultrasound, light, or other stresses. Kim et al (2000) prepared nanospheres with core-
shell structure from amphiphilic block copolymers by using PEO-PPO-PEO block copolymer (Pluronic) and poly(-caprolactone). Release behaviors of indomethacin from Pluronic/PCL block copolymeric nanospheres showed
temperature dependence and a sustained release pattern. Chilkoti et al (2002) described recursive directional ligation approach to synthesis of recombinant polypeptide carriers for the targeted delivery of radionuclides,
chemotherapeutics and biomolecular therapeutics to tumors by using a thermally responsive, elastin-like polypeptide as the drug carrier. Determan et al (2005) synthesized a family of amphiphilic ABCBA pentablock
copolymers based on the commercially available Pluronic® F127 block copolymers and various amine containing methacrylate monomers. The systems exhibited both temperature and pH responsiveness. They suggested that
the copolymers have high potential for applications in controlled drug delivery and non-viral gene therapy due to their tunable phase behavior and biocompatibility. Micro and nano systems for drug delivery applications can be
studied in the classes of micelles, liposomes, dendrimers, and particles of polymeric and ceramic materials as explained in the following sections.

Nanomaterials and Nanosystems for Biomedical Applications
NESRIN HASIRCI
Middle East Technical University, Faculty of Arts and Sciences, Department of Chemistry, Ankara 06531, Turkey

MICRO AND NANO SYSTEMS(3)

2009-06-08T23:27:00.000-07:00

2.MICRO AND NANO TECHNOLOGY IN MEDICINE

Micro and nanotechnology have significant applications in the biomedical area, such as drug delivery, gene therapy, novel drug synthesis, imaging, etc. In diagnostics and treatment of many disorders, micro-electro-mechanical systems (MEMS) and biocompatible electronic devices have great potentials. MEMS are formed by integration of mechanical elements, sensors, actuators and electronics on a common silicon wafer with microelectronics and micromachining technologies. Sensors collect information from the environment by measuring mechanical, thermal, biological, chemical, optical or magnetic parameters; electronics process these information and actuators respond by moving, positioning, regulating, pumping or filtering. Therefore a desired response occurs against the stresses and environment is controlled by the system.Use of nano devices in imaging is another important area especially in the detection of tumor cells. In principle, nanoparticles injected into the body detect cancer cells and bind to them. They behave as contrast agents making
the malignant area visible so that the anatomical contours of the cancer lesion can be defined. For this purpose iron- oxide nanoparticles whose surfaces were modified by amines were prepared by Shieh et al (2005) and a fast and prolonged inverse contrast effect was shown in the liver in vivo that lasted for more than 1 week. Medical applications of metallic nanoparticles were studied by different groups. For example Dua et al (2005) constructed a non- toxic, biomimetic interface for immobilization of living cells by mixing colloidal gold nanoparticles in carbon paste and studied its electrochemical exogenous effect on cell viability. Pal et al (2005) prepared gold nanoparticles in the presence of a biopolymer, sodium alginate by UV photoactivation. Carrara et al (2005)
prepared nanocom- posite materials of poly(o-anisidine) containing titanium dioxide nanoparticles, carbon black and multi-walled carbon nanotubes for biosensor applications. The synthe- sized materials were deposited in thin
films in order to investigate their impedance characteristics. Lee et al (2005) prepared ultrafine poly(acrylonitrile) (PAN) fibers containing silver nanoparticles. Silver ions in a PAN solution were reduced to produce Ag
nanoparticles and the resulting solution was electrospun into ultrafine PAN fibers. Morishita et al (2005) associated HVJ-E (hemagglutinating virus of Japan- envelope) with magnetic nanoparticles so that they can
potentially enhance its transfection efficiency in the presence of a magnetic force. It was reported that, heparin coated maghemite nano particles enhanced the transfection efficiency in the analysis of direct injection into the
mouse liver. They proposed that the systemcould potentially help overcome fundamental limitations to gene therapy in vivo.

Source:
Nanomaterials and Nanosystems for Biomedical Applications
NESRIN HASIRCI
Middle East Technical University, Faculty of Arts and Sciences, Department of Chemistry, Ankara 06531, Turkey

MICRO AND NANO SYSTEMS(2)

2009-06-08T23:19:00.000-07:00

1.INTRODUCTION

Development of metal, ceramic, polymer or materials of biological origin for use in medicine is a very important research area of the last decades. Scientists made great innovations in the production of artificial organs and tissues such as dental and orthopedic prostheses, artificial veins and heart valves, contact lenses, tissue engineering scaffolds, diagnostic systems, etc. As the knowledge on materials and biological systems improved,new areas such as interaction between the material and cells, effect of therapeutic agents at molecular level, the relation between the molecular structure and macroscopic properties became important research lines. Scientists are increasingly interested in mimicking the biological systems, under- standing cell-cell communications and modeling the structures that already exist in nature. This curiosity makes them search individual molecules, study interac- tions between the functional groups, signaling between the cells at micro and nano levels to be able to
control the properties of the artificial and biological systems. Technologies based on micro and nano levels involve synthesis and utilization of materials, devices and systems in which at least one dimension is less than 1 mm or in the submicron range, respectively.

Source:
Nanomaterials and Nanosystems for Biomedical Applications
NESRIN HASIRCI
Middle East Technical University, Faculty of Arts and Sciences, Department of Chemistry, Ankara 06531, Turkey

MICRO AND NANO SYSTEMS(1)

2009-06-08T23:15:00.000-07:00

MICRO AND NANO SYSTEMS IN BIOMEDICINE AND DRUG DELIVERY
NESRIN HASIRCI
Middle East Technical University, Faculty of Arts and Sciences, Department of Chemistry, Ankara 06531, Turkey

Micro and nano sytems sysnthesized from organic and inorganic materials are gaining great attention in biomedical applications such as design of biosensors, construction of imaging systems, synthesis of drug carrying and drug targeting devices, etc. Emulsions, suspensions, micelles, liposomes, dendrimers, polymeric and responsive systems are some examples for drug carrier devices. They have lots of advantages over conven- tional systems since they enhance the delivery, extend the bioactivity of the drug by protecting them from environmental effects in biological media, show minimal side effects, demonstrate high performance characteristics, and are more economical since minimum amount of expensive drugs are used. This chapter provides brief infor- mation about micro and nano systems used in biomedicine, nanobiotechnology and drug delivery

Keywords:micelles, liposomes, dendrimers, drug carriers, responsive polymers
Source:
Nanomaterials and Nanosystems for Biomedical ApplicationsNESRIN HASIRCIMiddle East Technical University, Faculty of Arts and Sciences, Department of Chemistry, Ankara 06531, Turkey

The Nanotechnology Revolution Nanomedicine(10)

2009-06-08T22:01:00.000-07:00

Molecular Repairs

Cells are made of billions of molecules, each built by molecular machines. These molecules self-assemble to form larger structures, many in dynamic patterns, perpetually disintegrating and reforming. Cell-surgery devices will be
able to make molecules of sorts that may be lacking, while destroying molecules that are damaged or present in excess. They will be able not only to remove viral genes, but to repair chemical and radiation-caused damage to the cell's own genes. Advanced cell surgery devices would be able to repair cells almost regardless of their initial state of damage.By activating and inactivating a cell's genes, they will be able to stimulate cell division and guide what types of cells are formed. This will be a great aid to cell herding and to healing tissues.
As surgeons today rely on the spontaneous, self-organizing ability of cells and tissues to join and heal the parts they manipulate, so cell-surgery devices will rely on the spontaneous self-organizing capabilities of molecules to join and "heal" the parts they put together. Healing of a surgical wound involves sweeping up dead cells, growing new cells, and a slow and genuinely painful process of tissue reorganization. In contrast, the joining of molecules
is almost instantaneous and occurs on a scale far below that of the most sensitive pain receptor. "Healing" will not begin after the repair devices have done their work, as it does in conventional surgery: rather, when they complete their work, the tissue will have been healed.

Healing Body and Limb
The ability to herd cells and to perform molecular repairs and cell surgery will open new vistas for medicine. These abilities apply on a small scale, but their effects can be large scale.Correcting ChemistryIn many diseases, the body as a whole suffers from misregulation of the signaling molecules that travel through
its fluids. Many are rare: Cushing's disease, Grave's disease, Paget's disease, Addison's disease, Conn's syndrome, Prader-Labhart-Willi syndrome. Others are common: millions of older women suffer from osteoporosis, the weakening of bones that can accompany lowered estrogen levels.Diabetes kills frequently enough to rank in the top ten causes of death in the United States; the number of individuals known to have it doubles every fifteen years. It is the leading cause of blindness in the United States, with other complications including kidney damage, cataracts, and cardiovascular damage. Today's molecular
medicine tries to solve these troubles by supplying missing molecules: diabetics inject additional insulin. While helpful, this doesn't cure the disease or eliminate all symptoms. In an era of molecular surgery, physicians could
choose instead to repair the defective organ, so it can regulate its own chemicals again, and to readjust the metabolic properties of other cells in the body to match. This would be a true healing, far better than today's partial fix.
Only now are researchers making progress on another frequent problem of metabolic regulation: obesity. Once this was thought to have one simple cause (consuming excess calories) and one main result (greater roundness
than favored by today's aesthetics), but both assumptions proved wrong. Obesity is a serious medical problem,increasing the risk of diabetes mellitus, osteoarthritis, degenerative diseases of the heart, arteries, and kidneys,
and shortening life expectancy. And the supposed cause, simple overeating, has been shown to be incorrect—something dieters had always suspected, as they watched thinner colleagues gorge and yet gain no weight.

The ability to lay in stores of fat was a great benefit to people once upon a time, when food supplies were irregular, nomadism and marauding bands made food storage difficult and risky, and starvation was a common cause of death. Our bodies are still adapted to that world, and regulate fat reserves accordingly. This is why dieting often has perverse effects. The body, when starved, responds by attempting to build up greater reserves of fat at its next opportunity. The main effect of exercise in weight reduction isn't to burn up calories, but to
signal the body to adapt itself for efficient mobility.
Obesity therefore seems to be a matter of chemical signals within the body, signals to store fat for famine or to become lean for motion. Nanomedicine will be able to regulate these signals in the bloodstream, and to adjust how individual cells respond to them in the body. The latter would even make possible the elusive "spot reduction program" to reshape the distribution of body fat.
Here, as with many potential applications of nanotechnology, the problem may be solved by other means first. Some problems, though, will almost surely require nanomedicine.New Organs and LimbsSo far we've seen how medical nanotechnology would be used in the simpler applications outside tissues—such as in the blood—then inside tissues, and finally inside cells. Consider how these abilities will fit together for victims of automobile and motorcycle accidents.
Nanomanufactured medical devices will be of dramatic value to those who have suffered massive trauma. Take the case of a patient with a crushed or severed spinal cord high in the back or in the neck. The latest research gives hope that when such patients are treated promptly after the injury, paralysis may be at least partially avoidable, sometimes. But those whose injuries weren't treated—including virtually all of today's patients—remain paralyzed. While research continues on a variety of techniques for attempting to aid a spontaneous healing process, prospects for reversing this sort of damage using conventional medicine remain bleak.
With the techniques discussed above, it will become possible to remove scar tissue and to guide cell growth so as to produce healthy arrangements of the cells on a microscopic scale. With the right molecular-scale poking and
prodding of the cell nucleus, even nerve cells of the sorts found in the brain and spinal cord can be induced to divide. Where nerve cells have been destroyed, there need be no shortage of replacements. These technologies will eventually enable medicine to heal damaged spinal cords, reversing paralysis.
The ability to guide cell growth and division and to direct the organization of tissues will be sufficient to regrow entire organs and limbs, not merely to repair what has been damaged. This will enable medicine to restore physical health despite the most grievous injuries.
If this seems hard to believe, recall that medical advances have shocked the world before now. To those in the past, the idea of cutting people open with knives painlessly would have seemed miraculous, but surgical anesthesia is now routine. Likewise with bacterial infections and antibiotics, with the eradication of smallpox, and the vaccine for polio: Each tamed a deadly terror, and each is now half-forgotten history. Our gut sense of what seems likely has little to do with what can and cannot be done by medical technology. It has more to do with our habitual fears, including the fear of vain hopes. Yet what amazes one generation seems obvious and even boring to the next. The first baby born after each breakthrough grows up wondering what all the excitement was about.
Besides, nano-scale medicine won't be a cure-all. Consider a fifty-year-old mentally retarded man, with a mind like a two-year-old's, or a woman with a brain tumor that has spread to the point that her personality has changed: How could they be "healed"? No healing of tissues could replace a missed lifetime of adult experience, nor can it replace lost information from a severely damaged brain. The best physicians could do would be to bring the patients to some physically healthy condition. One can wish for more, but sometimes it won't be
possible.
First AidThroughout the centuries, medicine has been constrained to maintain functioning tissues, since once tissues stop functioning, they can't heal themselves. With molecular surgery to carry out the healing directly, medical priorities change drastically—function is no longer absolutely necessary. In fact, a physician able to use molecular surgery would prefer to operate on nonfunctioning, structurally stable tissue than on tissue that has been allowed to continue malfunctioning until its structure was lost.
Brain tumors are an example: They destroy the brain's structure, and with it the patient's skills, memories, and personality. Physicians in the future should be able to immediately interrupt this process, to stop the functioning of the brain to stabilize the patient for treatment.
Techniques available today can stop tissue function while preserving tissue structure. Greg Fahy, in his work on organ preservation at the American Red Cross, is developing a technique for vitrifying animal kidneys—making
them into a low-temperature, crystal-free glass—with the goal of maintaining their structure such that, when brought back to room temperature, they can be transplanted. Some kidneys have been cooled to -30 ?C, warmed back up, and then functioned after transplantation.
A variety of other procedures can also stabilize tissues on a long-term basis. These procedures enable many cells—but not whole tissues—to survive and recover without help; advanced molecular repair and cell surgery will
presumably tip the balance, enabling cells, tissues, and organs to recover and heal. When applied to stabilizing a whole patient, such a condition can be called biostasis. A patient in biostasis can be kept there indefinitely until
the required medical help arrives. So in the future, the question "Can this patient be restored to health?" will be answered "Yes, if the patient's brain is intact, and with it the patient's mind."
Sandra Lee Adamson of the National Space Society has her eyes on distant goals. Some have proposed that travel to the stars would take generations, preventing anyone on Earth from ever making the trip. But she notes that
biostasis will "give hope to some fearless adventurers who will risk suspension and subsequent reanimation so they can see the stars for themselves."
Plague InsuranceMedical nanotechnologies promise to extend healthy life, but if history is any guide, they may also avert sudden massive death. The word plague is rarely heard today, except in relation to AIDS; it calls up visions of the Black Death of the Middle Ages, when one third of Europe died in 1346-50. A virulent influenza struck in 1918, half lost in the news of the First World War: how many of us realize that it killed at least 20 million? People often act as
though plagues were gone for good, as if sanitation and antibiotics had vanquished them. But as doctors are forever telling their patients, antibiotics kill bacteria, but are useless for viruses. The flu, the common cold,
herpes, and AIDS—none has a really effective treatment, because all are caused by viruses. In some African countries, as much as 10 percent of the population is estimated to be infected with the AIDS-causing HIV virus.
Without a cure soon, the steep rise in deaths from AIDS still lies in the future. AIDS stands as a grim reminder that the great plagues of history are not behind us.
The Threat New diseases continue to appear today as they have throughout history. Today's population, far larger than that of any previous century, provides a huge, fertile territory for their spread.
Today's transportation systems can spread viruses from continent to continent in a single day. When ships sailed or churned their way across the seas, an infected passenger was likely to show full-blown disease before arrival,
permitting quarantine. But few diseases can be guaranteed to show themselves in the hours of a single aircraft flight.So far as is known, every species of organism, from bacterium to whale, is afflicted with viruses. Animal viruses
sometimes "jump the species gap" to infect other animals, or people. Most scientists believe that the ancestors of the AIDS virus could, until recently, infect only certain African monkeys. Then these viruses made the interspecies
jump. A similar jump occurred in the 1960s when scientists in West Germany, working with cells from monkeys in Uganda, suddenly fell ill. Dozens were infected, and several died of a disease that caused both blood clots and
bleeding, caused by what is now named the Marburg virus. What if the Marburg virus had spread with a sneeze, like influenza or the common cold?
We think of human plagues as a health problem, but when they hit our fellow species, we tend to see them from an environmental perspective. In the late 1980s, over half the harbor-seal population in large parts of the North
Sea suddenly died, leading many at first to blame pollution. The cause, though, appears to be a distemper virus that made the jump from dogs. Biologists worry that the virus could infect seal species around the world, since distemper virus can spread by aerosols—that is, by coughing—and seals live in close physical contact. So far its mortality rate has been 60 to 70 percent.

What of AIDS itself: Could it change and give rise to a form able to spread, say, as colds do? Nobel Laureate Howard M. Temin has said, "I think that we can very confidently say that this can't happen." Nobel Laureate
Joshua Lederberg, president of Rockefeller University in New York City, replied, "I don't share your confidence about what can and cannot happen." He points out that "there is no reason a great plague could not happen again. . . .We live in evolutionary competition with microbes—bacteria and viruses. There is no guarantee that we will be the survivors."
Our Inadequate AbilitiesBacterial diseases are mostly controllable today. Sanitation limits the ways in which plague can spread. These measures are just good enough to lull us into imagining the problem is solved.
Viruses are common, viruses mutate; some spread through the air, and some are deadly. Plagues show that fast-spreading diseases can be deadly, and effective antiviral drugs are still rare.
The only really effective treatments for viral diseases are preventive, not curative. They work either by preventing exposure, or by exposing the body beforehand to dead or harmless or fragmentary forms of the virus, to prepare
the immune system for future exposure. As the long struggle for an AIDS vaccine shows, one cannot count on modern medicine to identify a new virus and produce an effective vaccine within a single month or year or even a
single decade. But influenza epidemics spread fast, and Marburg II or AIDS II or something entirely new and deadly may do the same.
Doing BetterThe deaths from the next great plague could have begun in a village last week, or could begin next year, or a year before we learn to deal with new viral illnesses promptly and effectively. With luck, the plague will wait until
a year after.Immune machines could be set to kill a new virus as soon as it is identified. The instruments nanotechnology brings will make viral identification easy. Some day, the means will be in place to defend human life against viral
catastrophe.
From eliminating viruses to repairing individual cells, improving our control of the molecular world will improve health care. Immune machines working in the bloodstream seem about as complex as some engineering projects human beings have already completed—projects like large satellites. Other medical nanotechnologies seem to be of a higher order of complexity.
On Solving Hard ProblemsSomewhere in the progression from relatively simple immune devices to molecular surgery, we've crossed the fuzzy line between systems that teams of clever biomedical engineers could design in a reasonable length of time and ones that might take decades or prove impossibly complex. Designing a nanomachine capable of entering a cell, reading its DNA, finding and removing a deadly viral DNA sequence, and then restoring the cell to normal would be a monumental job. Such tasks are advanced applications of nanotechnology, far beyond mere computers, manufacturing equipment, and half-witted "smart materials."
To succeed within a reasonable number of years, we may need to automate much of the engineering process, including software engineering. Today's best expert systems are nowhere near sophisticated enough. The software must be able to apply physical principles, engineering rules, and fast computation to generate and test new designs. Call it automated engineering.
Automated engineering will prove useful in advanced nanomedicine because of the sheer number of small problems to be solved. The human body contains hundreds of kinds of cells forming a huge number of tissues and organs. Taken as a whole (and ignoring the immune system), the body contains hundreds of thousands of different kinds of molecules. Performing complex molecular repairs on a damaged cell might require solving millions of separate, repetitive problems. The molecular machinery in cell surgery devices will need to be
controlled by complex software, and it would be best to be able to delegate the task of writing that software to an automated system. Until then, or until a lot of more conventional design work gets done, nanomedicine will have to focus on simpler problems.
AgingWhere does aging fit in the spectrum of difficulty? The deterioration that comes with aging is increasingly recognized as a form of disease, one that weakens the body and makes it susceptible to a host of other diseases.
Aging, in this view, is as natural as smallpox and bubonic plague, and more surely fatal. Unlike bubonic plague, however, aging results from internal malfunctions in the molecular machinery of the body, and a medical
condition with so many different symptoms could be complex.
Surprisingly, substantial progress is being made with present techniques, without even a rudimentary ability to perform cell surgery in a medical context. Some researchers believe that aging is primarily the result of a fairly
small number of regulatory processes, and many of these have already been shown to be alterable. If so, aging may be tackled successfully before even simple cell repair is available. But the human aging process is not well
enough understood to enable a confident projection of this; for example, the number of regulatory processes is not yet known. A thorough solution may well require advanced nanotechnology-based medicine, but a thorough solution seems possible. The result would not be immortality, just much longer, healthier lives for those who want them.
Restoring SpeciesA challenging problem related to medicine (and to biostasis) is that of species restoration. Today, researchers are carefully preserving samples from species now becoming extinct. In some cases, all they have are tissue samples. For other species, they've been able to save germ cells in the hope that they will be able to implant fertilized eggs into related species and thus bring the (nearly?) extinct species back.Each cell typically contains the organism's complete genetic information, but what can be done with this? Many researchers today collect samples for preservation thinking only of the implantation scenario: one that they know has already been made to work. Other researchers are taking a broader view: the Center for Genetic Resources
and Heritage at the University of Queensland is a leader in the effort. Daryl Edmondson, coordinator of the gene library, explains that the center is unique because it will "actively collect data. Most other libraries simply collate
their own collections." Director John Mattick describes it as a "genetic Louvre" and points out that if genes from today's endangered species aren't preserved, "subsequent generations will see we had the technology to keep
[DNA] software and will ask why we didn't do it." With this information and the sorts of molecular repair and cell-surgery capabilities we have discussed, lost species can someday be returned to active life again as habitats are restored.
One such center isn't enough: the Queensland center focuses on Australian species (naturally enough) and has limited funds. Besides, anything so precious as the genetic information of an endangered species should be stored
in many separate locations for safety. We need to take out an insurance policy on Earth's genetic diversity with a broader network of genetic libraries, concentrating special attention on gathering biological samples from the fast
-disappearing rain forests. Scientific study can wait: the urgency of the situation calls for a vacuum-cleaner approach. The Foresight Institute is promoting this effort through its BioArchive Project; interested readers can
write to the address at the end of the Afterword.

Source
>http://inventors.about.com/gi/dynamic/offsite.htm?zi=1/XJ/Ya&sdn=inventors&zu=http%3A%2F%
2Fen.wikipedia.org%2Fwiki%2FNanotechnology

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2009-06-08T21:56:00.000-07:00

Working on Cells

Moving through tissues without leaving a trail of disruption will require devices able to manipulate and direct the motions of cells, and to repair them. Much remains to be learned—and will be easy to learn with nanoscale tools—but today's knowledge of cells is enough for a start on the problem of how to do surgery on cells.
Cell biology is a booming field, even today. Cells can be made to live and grow in laboratory cultures if they are placed in a liquid with suitable nutrients, oxygen, and the rest. Even with today's crude techniques, much has been learned about how cells respond to different chemicals, to different neighbors, and even to being poked and cut with needles. Conducting a rough sort of surgery on individual cells has been routine for many years in scientific laboratories.
Today, researchers can inject new DNA into cells using a tiny needle; small punctures in a cell membrane automatically reseal. But both these techniques use tools that on a cellular scale are large and clumsy—like doing surgery with an ax or a wrecking ball, instead of a scalpel. Nano-scale tools will enable medical procedures involving delicate surgery on individual cells.
Eliminating Viruses by Cell SurgerySome viral diseases will respond to treatments that destroy viruses in the nose and throat, or in the bloodstream.
The flu and common cold are examples. Many others would be greatly improved by this, but not eliminated. All viruses work by injecting their genes into a cell and taking over its molecular machinery, using it to produce more viruses. This is part of what makes viral illnesses so hard to treat—most of the action is performed by the body's own molecular machines, which can't be interfered with on a wholesale basis. When the immune system deals with a viral illness, it both attacks free virus particles before they enter cells, and attacks infected cells before they can churn out too many more virus particles.
Some viruses, though, insert their genes among the genes of the cell, and lay low. The cell can seem entirely normal to the immune system, for months or years, until the viral genes are triggered into action and begin the infective process anew. This pattern is responsible for the persistence of herpes nfections, and for the slow, deadly progress of AIDS.
These viruses can be eliminated by molecular-level cellular surgery. The required devices could be small enough to fit entirely within the cell, if need be. Greg Fahy, who heads the Organ Cryopreservation Project at the American Red Cross's Jerome Holland Transplantation Laboratory, writes, "Calculations imply that molecular sensors, molecular computers, and molecular effectors can be combined into a device small enough to fit easily inside a single cell and powerful enough to repair molecular and structural defects (or to degrade foreign structures such as viruses and bacteria) as rapidly as they accumulate. . . .There is no reason such systems cannot be built and function as designed."
Equally well, a cell surgery device located outside a cell could reach through the membrane with long probes. At the ends of the probes would be tools and sensors along with, perhaps, a small auxiliary computer. These would
be able to reach through multiple membranes, unpackage and uncoil DNA, read it, repackage it, and recoil it, "proofreading" the DNA by comparing the sequences in one cell to the sequences of other cells.
On reading the genetic sequence spelling out the message of the AIDS virus, a molecular surgery machine could be programmed to respond like an immune machine, destroying the cell. But it would seem to make more sense simply to cut out the AIDS virus genes themselves, and reconnect the ends as they were before infection. By doing this, and killing any viruses found in the cell, the procedure would restore the cell to health.

Source:
>1991 "Nanomedicine," Chapter 10, Unbounding the Future (K. Eric Drexler, Christine Peterson, Gayle Pergamit)
>Dec. 1994 "Nanotechnology and Medicine" (Ralph C. Merkle) >http://inventors.about.com/gi/dynamic/offsite.htm?zi=1/XJ/Ya&sdn=inventors&zu=http%3A%2F%
2Fen.wikipedia.org%2Fwiki%2FNanotechnology

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Rebuilding Tissues

Again, skin provides easy examples and may be a natural place to start in practice. People often want hair where they have bare skin, and bare skin where they have hair. Cell herding machines could move or destroy hair follicle
cells to eliminate an unwanted hair, or grow more of the needed cells and arrange them into a working follicle where a hair is desired. By adjusting the size of the follicle and the properties of some of the cells, hairs could be
made coarser, or finer, or straighter, or curlier. All these changes would involve no pain, toxic chemicals, or stench. Cell-herding devices could move down into the living layers of skin, removing unwanted cells, stimulating the growth of new cells, narrowing unnaturally prominent blood vessels, insuring good circulation by guiding the growth of any needed normal blood vessels, and moving cells and fibers around so as to eliminate even deep wrinkles.
At the opposite end of the spectrum, cell herding will revolutionize treatment of life-threatening conditions. For example, the most common cause of heart disease is reduced or interrupted supply of blood to the heart muscle.
In pumping oxygenated blood to the rest of the body, the heart diverts a portion for its own use though the coronary arteries. When these blood vessels become constricted, we speak of coronary-artery disease. When they are blocked, causing heart muscle tissue to die, we speak of someone "having a coronary," another term for heart attack.
Devices working in the bloodstream could nibble away at atherosclerotic deposits, widening the affected blood vessels. Cell herding devices could restore artery walls and artery linings to health, by ensuring that the right cells
and supporting structures are in the right places. This would prevent most heart attacks.
But what if a heart attack has already destroyed muscle tissue, leaving the patient with a scarred, damaged, and poorly functioning heart? Once again, cell-herding devices could accomplish repairs, working their way into the
scar tissue and removing it bit by bit, replacing it with fresh muscle fiber. If need be, this new fiber can be grown by applying a series of internal molecular stimuli to selected heart muscle cells to "remind" them of the instructions for growth that they used decades earlier during embryonic development.
Cell-herding capabilities should also be able to deal with the various forms of arthritis. Where this is due to attacks from the body's own immune system, the cells producing the damaging antibodies can be identified and eliminated. Then a cell-herding system would work inside the joint where it would remove diseased tissues, calcified spurs, and so forth, then rework patterns of cells and intercellular material to form a healthy, smoothly working, and pain-free joint. Clearly, learning to repair hearts and learning to repair joints will have some basic technologies in common, but much of the research and development will have to be devoted to specific tissues and specific circumstances. A similar process—but again, specially adapted to the circumstances at hand—could
be used to strengthen and reshape bone, correcting osteoporosis.

In dentistry, this sort of process could be used to fill cavities, not with amalgam, but with natural dentin and enamel. Reversing the ravages of periodontal disease will someday be straightforward, with nanomedical devices
to clean pockets, join tissues, and guide regrowth. Even missing teeth could be regrown, with enough control over cell behavior.
Source:
>1991 "Nanomedicine," Chapter 10, Unbounding the Future (K. Eric Drexler, Christine Peterson, Gayle Pergamit)
>Dec. 1994 "Nanotechnology and Medicine" (Ralph C. Merkle) >http://inventors.about.com/gi/dynamic/offsite.htm?zi=1/XJ/Ya&sdn=inventors&zu=http%3A%2F%
2Fen.wikipedia.org%2Fwiki%2FNanotechnology

The Nanotechnology Revolution Nanomedicine(7)

2009-06-08T21:48:00.000-07:00

Working Within Tissues

In most parts of the body, the finest blood vessels, capillaries, pass within a few cell diameters of every point. Certain white blood cells can leave these vessels to move among the neighboring cells. Immune machines and similar devices, being even smaller, could do likewise. In some tissues, this will be easy, in some harder, but with careful design and testing, essentially any point of the body should become accessible for healing repairs.
Merely fighting organisms in the bloodstream would be a major advance, cutting their numbers and inhibiting their spread. Roving medical nanomachines, though, will be able to hunt down invaders throughout the body and eliminate them entirely.
Eliminating InvadersCancers are a prime example. The immune system recognizes and eliminates most potential cancers, but some get by. Physicians can recognize cancer cells by their appearance and by molecular markers, but they cannot always remove them all through surgery, and often cannot find a selective poison. Immune machines, however, will have no difficulty identifying cancer cells, and will ultimately be able to track them down and destroy them
wherever they may be growing. Destroying every cancer cell will cure the cancer.
Bacteria, protozoa, worms, and other parasites have even more obvious molecular markers. Once identified, they could be destroyed, ridding the body of the disease they cause. Immune machines thus could deal with tuberculosis, strep throat, leprosy, malaria, amoebic dysentery, sleeping sickness, river blindness, hookworm, flukes, candida, valley fever, antibiotic-resistant bacteria, and even athlete's foot. All are caused by invading cells or larger organisms (such as worms). Health officials estimate that parasitic diseases, common in the Third World, affect more than one billion people. For many of these diseases, no satisfactory drug treatment exists. All can eventually be eliminated as threats to human health by a sufficiently advanced form of nanomedicine.
Herding CellsDestroying invaders will be helpful, but injuries and structural problems pose other problems. Truly advanced medicine will be able to build up and restructure tissues. Here, medical nanodevices can stimulate and guide the
body's own construction and repair mechanisms to restore healthy tissue.
What is healthy tissue? It consists of normal cells in normal patterns in a normal matrix all organized in a normal relationship to the surrounding tissues. Surgeons today (with their huge, crude tools) can fix some problems at
the tissue level. A wound disrupts the healthy relationship between two different pieces of tissue, and surgical glues and sutures can partly remedy this problem by holding the tissues in a position that promotes healing.
Likewise, coronary artery bypass surgery brings about a more healthy overall configuration of tissues—one that provides working plumbing to supply blood to the heart muscle. Surgeons cut and stitch, but then they must rely
on the tissue to heal its wounds as best it can.
Healing establishes healthy relationships on a finer scale. Cells must divide, grow, migrate, and fill gaps. They must reorganize to form properly connected networks of fine blood vessels. And cells must lay down materials to form the structural, intercellular matrix—collagen to provide the proper shape and toughness, or mineral grains to provide rigidity, as in bone. Often, they lay down unwanted scar tissue instead, blocking proper healing.
With enough knowledge of how these processes work (and nanoinstruments can help gather that knowledge) and with good enough software to guide the process—a more difficult challenge—medical nanomachines will be able
to guide this healing process. The problem here is to guide the motion and behavior of a mob of active, living cells—a process that can be termed cell herding.
Cells respond to a host of signals from their environment: to chemicals in the surrounding fluids, to signal molecules on neighboring cells, and to mechanical forces applied to them. Cell-herding devices would use these signals to spur cell division where it is needed and to discourage it where it is not. They would nudge cells to encourage them to migrate in appropriate directions, or would simply pick them up, move them along, and deliver them where needed, encouraging them to nestle into a proper relationship with their neighbors. Finally, they would stimulate cells to surround themselves with the proper intercellular-matrix materials. Or—like the owner of a small dog who, on a cold day, wraps the beast in a wool jacket—they would directly build the proper
surrounding structures for the cell in its new location.
In this way, cooperating teams of cell-herding devices could guide the healing or restructuring of tissues, ensuring that their cells form healthy patterns and a healthy matrix and that those tissues have a healthy relationship to their surroundings. Where necessary, cells could even be adjusted internally, as we will discuss later.

Source:
>1991 "Nanomedicine," Chapter 10, Unbounding the Future (K. Eric Drexler, Christine Peterson, Gayle Pergamit)
>Dec. 1994 "Nanotechnology and Medicine" (Ralph C. Merkle) >http://inventors.about.com/gi/dynamic/offsite.htm?zi=1/XJ/Ya&sdn=inventors&zu=http%3A%2F%
2Fen.wikipedia.org%2Fwiki%2FNanotechnology

The Nanotechnology Revolution Nanomedicine(6)

2009-06-08T21:42:00.000-07:00

Working Outside Tissues

One approach to nanomedicine would make use of microscopic mobile devices built using molecular-manufacturing equipment. These would resemble the ecosystem protectors and mobile cleanup machines discussed in the last chapter. Like them, they would either be biodegradable, self-collecting, or collected by something else once they were done working. Like them, they would be more difficult to develop than simple,fixed-location nanomachines, yet clearly feasible and useful. Development will start with the simpler applications, so let's begin by looking at what can be done without entering living tissues.
The skin is the body's largest organ, and its exposed position subjects it to a lot of abuse. This exposed position,though, also makes it easier to treat. Among the earlier applications of molecular manufacturing may be those popular, quasimedical products, cosmetics. A cream packed with nanomachines could do a better and more selective job of cleaning than any product can today. It could remove the right amount of dead skin, remove excess oils, add missing oils, apply the right amounts of natural moisturizing compounds, and even achieve the elusive goal of "deep pore cleaning" by actually reaching down into pores and cleaning them out. The cream could be a smart material with smooth-on, peel-off convenience.
The mouth, teeth, and gums are amazingly troublesome. Today, daily dental care is an endless cycle of brushing and flossing, of losing ground to tooth decay and gum disease as slowly as possible. A mouthwash full of smart nanomachines could do all that brushing and flossing do and more, and with far less effort—making it more likely to be used.
This mouthwash would identify and destroy pathogenic bacteria while allowing the harmless flora of the mouth to flourish in a healthy ecosystem. Further, the devices would identify particles of food, plaque, or tartar, and lift them from teeth to be rinsed away. Being suspended in liquid and able to swim about, devices would be able to reach surfaces beyond reach of toothbrush bristles or the fibers of floss. As short-lifetime medical nanodevices, they could be built to last only a few minutes in the body before falling apart into materials of the sort found in foods (such as fiber). With this sort of daily dental care from an early age, tooth decay and gum disease would likely never arise. If under way, they would be greatly lessened.
Going beyond this superficial treatment would involve moving among and modifying cells. Let's consider what can be done with this treatment inside the body, but outside the body's tissues. The bloodstream carries everything from nutrients to immune-system cells, with chemical signals and infectious organisms besides.Medical nanodevices could augment the immune system by finding and disabling unwanted bacteria and viruses.
The immune device in the foreground has found a virus; the other has touched a red blood cell. Adapted from Scientific American, January 1988. Here, it is useful to think in terms of medical nanomachines that resemble small submarines. Each of these is large enough to carry a nanocomputer as powerful as a mid-1980s mainframe, along with a huge database (a billion bytes), a complete set of instruments for identifying biological surfaces, and tools
for clobbering viruses, bacteria, and other invaders. Immune cells, as we've seen, travel through the bloodstream checking surfaces for foreignness and—when working properly—attacking and eliminating what should not be
there. These immune machines would do both more and less. With their onboard sensors and computers, they will be able to react to the same molecular signals that the immune system does, but with greater discrimination.
Before being sent into the body on their search-and-destroy mission, they could be programmed with a set of characteristics that lets them clearly distinguish their targets from everything else. The body's immune system can
respond only to invading organisms that had been encountered by that individual's body. Immune machines,however, could be programmed to respond to anything that had been encountered by world medicine.
Immune machines can be designed for use in the bloodstream or the digestive tract (the mouthwash described above used these abilities in hunting down harmful bacteria). They could float and circulate, as antibiotics do,
while searching for intruders to neutralize. To escape being engulfed by white blood cells making their own patrols, immune machines could display standard molecules on their surface-molecules the body knows and trusts already—like a fellow police officer wearing a familiar uniform.
When an invader is identified, it can be punctured, letting its contents spill out and ending its effectiveness. If the contents were known to be hazardous by themselves, then the immune machine could hold on to it long enough
to dismantle it more completely.
How will these devices know when it's time to depart? If the physician in charge is sure the task will be finished within, say, one day, the devices prescribed could be of a type designed to fall apart after twenty-four hours. If the treatment time needed is variable, the physician could monitor progress and stop action at the appropriate time by sending a specific molecule—aspirin perhaps, or something even safer—as a signal to stop work. The inactivated devices would then be cleared out along with other waste eliminated from the body.

Source:
>1991 "Nanomedicine," Chapter 10, Unbounding the Future (K. Eric Drexler, Christine Peterson, Gayle Pergamit)
>Dec. 1994 "Nanotechnology and Medicine" (Ralph C. Merkle) >http://inventors.about.com/gi/dynamic/offsite.htm?zi=1/XJ/Ya&sdn=inventors&zu=http%3A%2F%
2Fen.wikipedia.org%2Fwiki%2FNanotechnology

The Nanotechnology Revolution Nanomedicine(5)

2009-06-08T21:37:00.000-07:00

Nanotechnology in Medicine

Developments in nanotechnology will result in improved medical sensors. As protein chemist Bill DeGrado notes, "Probably the first use you may see would be in diagnostics: being able to take a tiny amount of blood from somebody, just a pinprick, and diagnose for a hundred different things. Biological systems are already able to do that, and I think we should be able to design molecules or assemblies of molecules that mimic the biological system."
In the longer term, though, the story of nanotechnology in medicine will be the story of extending surgical control to the molecular level. The easiest applications will be aids to the immune system, which selectively attack
invaders outside tissues. More difficult applications will require that medical nanomachines mimic white blood cells by entering tissues to interact with their cells. Further applications will involve the complexities of molecular-level surgery on individual cells.
As we look at how to solve various problems, you'll notice that some that look difficult today will become easy,while others that might seem easier turn out to be more difficult. The seeming difficulty of treating disorders is always changing: Once polio was frequent and incurable, today it is easily prevented. Syphilis once caused steady physical decline leading to insanity and death; now it is cured with a shot.
Athlete's foot has never been seen as a great scourge, yet it remains hard to cure. Likewise with the common cold. This pattern will continue: Deadly diseases may be easily dealt with, while minor ills remain incurable, or vice versa. As we will see, a mature nanotechnology-based medicine will be able to deal with almost any physical problem, but the order of difficulty may be surprising. Nature cares nothing for our sense of appropriateness. Horribleness and difficulty just aren't the same thing.

Source:
>1991 "Nanomedicine," Chapter 10, Unbounding the Future (K. Eric Drexler, Christine Peterson, Gayle Pergamit)
>Dec. 1994 "Nanotechnology and Medicine" (Ralph C. Merkle) >http://inventors.about.com/gi/dynamic/offsite.htm?zi=1/XJ/Ya&sdn=inventors&zu=http%3A%2F%
2Fen.wikipedia.org%2Fwiki%2FNanotechnology

The Nanotechnology Revolution Nanomedicine(4)

2009-06-08T21:25:00.000-07:00

Medicine Today

When the body's working, building, and battling goes awry, we turn to medicine for diagnosis and treatment. Today's methods, though, have obvious shortcomings.Crude MethodsDiagnostic procedures vary widely, from asking a patient questions, through looking at X-ray shadows, through
exploratory surgery and the microscopic and chemical analysis of materials from the body. Doctors can diagnose many ills, but others remain mysteries. Even a diagnosis does not imply understanding: doctors could diagnose
infections before they knew about germs, and today can diagnose many syndromes with unknown causes. After years of experimentation and untold loss of life, they can even treat what they don't understand—a drug may
help, though no one knows why.Leaving aside such therapies as heating, massaging, irradiating, and so forth, the two main forms of treatment
are surgery and drugs. From a molecular perspective, neither is sophisticated.
Surgery is a direct, manual approach to fixing the body, now practiced by highly trained specialists. Surgeons sew together torn tissues and skin to enable healing, cut out cancer, clear out clogged arteries, and even install pacemakers and replacement organs. It's direct, but it can be dangerous: anesthetics, infections, organ rejection, and missed cancer cells can all cause failure. Surgeons lack fine-scale control. The body works by means of molecular machines, most working inside cells. Surgeons can see neither molecules nor cells, and can repair neither.

Drug therapies affect the body at the molecular level. Some therapies—like insulin for diabetics—provide materials the body lacks. Most—like antibiotics for infections—introduce materials no human body produces. A drug consists of small molecules; in our simulated molecular world, many would fit in the palm of your hand. These molecules are dumped into the body (sometimes directed to a particular region by a needle or the like), where they mix and wander through blood and tissue. They typically bump into other molecules of all sorts in all places,but only stick to and affect molecules of certain kinds.
Antibiotics like penicillin are selective poisons. They stick to molecular machines in bacteria and jam them, thus fighting infection. Viruses are a harder case because they are simpler and have fewer vulnerable molecular
machines. Worms, fungi, and protozoa are also difficult, because their molecular machines are more like those found in the human body, and hence harder to jam selectively. Cancer is the most difficult of all. Cancerous
growths consist of human cells, and attempts to poison the cancer cells typically poison the rest of the patient as well.
Other drug molecules bind to molecules in the human body and modify their behavior. Some decrease the secretion of stomach acid, others stimulate the kidneys, many affect the molecular dynamics of the brain.Designing drug molecules to bind to specific targets is a growth industry today, and provides one of the many short-term payoffs that is spurring developments in molecular engineering.

Limited Abilities
Current medicine is limited both by its understanding and by its tools. In many ways, it is still more an art than a science. Mark Pearson of Du Pont points out, "In some areas, medicine has become much more scientific, and in others not much at all. We're still short of what I would consider a reasonable scientific level. Many people don't realize that we just don't know fundamentally how things work. It's like having an automobile, and hoping that by taking things apart, we'll understand something of how they operate. We know there's an engine in the front and we know it's under the hood, we have an idea that it's big and heavy, but we don't really see the rings that allow pistons to slide in the block. We don't even understand that controlled explosions are responsible for providing the energy that drives the machine."
Better tools could provide both better knowledge and better ways to apply that knowledge for healing. Today's surgery can rearrange blood vessels, but is far too coarse to rearrange or repair cells. Today's drug therapies can target some specific molecules, but only some, and only on the basis of type. Doctors today can't affect molecules in one cell while leaving identical molecules in a neighboring cell untouched because medicine today cannot apply surgical control to the molecular level.

Source:
>1991 "Nanomedicine," Chapter 10, Unbounding the Future (K. Eric Drexler, Christine Peterson, Gayle Pergamit)
>Dec. 1994 "Nanotechnology and Medicine" (Ralph C. Merkle) >http://inventors.about.com/gi/dynamic/offsite.htm?zi=1/XJ/Ya&sdn=inventors&zu=http%3A%2F%
2Fen.wikipedia.org%2Fwiki%2FNanotechnology

The Nanotechnology Revolution Nanomedicine(3)

2009-06-08T21:22:00.000-07:00

The Body As BattlefieldAssaults from outside the body turn it into a battlefield where the aggressors sometimes get the upper hand.
From parasitic worms to protozoa to fungi to bacteria to viruses, organisms of many kinds have learned to live by
entering the body and using their molecular machinery to build more of themselves from the body's building
blocks. To meet this onslaught, the body musters the defenses of the immune system—an armada of its own
molecular machines. Your body's own amoebalike white blood cells patrol the bloodstream and move out into
tissues, threading their way between other cells, searching for invaders.
How can the immune system distinguish the hundreds of kinds of cells that should be in the body from the
invading cells and viruses that shouldn't? This has been the central question of the complex science of
immunology. The answer, as yet only partially understood, involves a complex interplay of molecules that
recognize other molecules by sticking to them in a selective fashion. These include free-floating antibodies—which
are a bit like bumbling guided missiles—and similar molecules that are bound to the surface of white blood cells
and other cells of the immune system, enabling them to recognize foreign surfaces on contact.
This system makes life possible, defending our bodies from the fate of meat left at room temperature. Still, it lets
us down in two basic ways.
First, the immune system does not respond to all invaders, or responds inadequately. Malaria, tuberculosis,
herpes, and AIDS all have their strategies for evading destruction. Cancer is a special case in which the invaders
are altered cells of the body itself, sometimes successfully masquerading as healthy cells and escaping detection.
Second, the immune system sometimes overresponds, attacking cells that should be left alone. Certain kinds of
arthritis, as well as lupus and rheumatic fever, are caused by this mistake. Between attacking when it shouldn't
and not attacking when it should, the immune system often fails, causing suffering and death.

Source:
>1991 "Nanomedicine," Chapter 10, Unbounding the Future (K. Eric Drexler, Christine Peterson, Gayle Pergamit)
>Dec. 1994 "Nanotechnology and Medicine" (Ralph C. Merkle) >http://inventors.about.com/gi/dynamic/offsite.htm?zi=1/XJ/Ya&sdn=inventors&zu=http%3A%2F%
2Fen.wikipedia.org%2Fwiki%2FNanotechnology

The Nanotechnology Revolution Nanomedicine(2)

2009-06-08T21:17:00.000-07:00

The Body As Construction Site
In growing, healing, and renewing tissue, the body is a construction site. Cells take building materials from the bloodstream. Molecular machinery programmed by the cell's genes uses these materials to build biological structures: to lay down bone and collagen, to build whole new cells, to renew skin, and to heal wounds.
With the exception of tooth fillings and other artificial implants, everything in the human body is constructed by molecular machines. These molecular machines build molecules, including more molecular machines. They clear away structures that are old or out of place, sometimes using machinery like digestive enzymes to take structures apart.
During tissue construction, whole cells move about, amoebalike: extending part of themselves forward, attaching, pulling their material along, and letting go of the former attachment site behind them. Individual cells contain a dynamic pattern of molecules made of components that can break down but can also be replaced. Some molecular machines in the cell specialize in digesting molecules that show signs of damage, allowing them to be replaced by fresh molecules made according to genetic instructions. Components inside cells form their complex patterns by self-assembly, that is, by sticking to the proper partners.
Failures in construction increase as we age. Teeth wear and crack and aren't replaced; hair follicles stop working; skin sags and wrinkles. The eye's shape becomes more rigid, ruining close vision. Younger bodies can knit together broken bones quickly, making them stronger than before, but osteoporosis can make older bones so fragile that they break under minor stress.
Sometimes construction is botched from the beginning due to a missing or defective genetic code. In hemophilia, bleeding fails to stop due to the lack of blood clotting factor. Construction of muscle tissue is disrupted in 1 in 3,300 male births by muscular dystrophy, in which muscles are gradually replaced by scar tissue and fat; the molecule "dystrophin" is missing. Sickle cell anemia results from abnormal hemoglobin molecules.
Paraplegics and quadriplegics know that some parts of the body don't heal well. The spinal cord is an extreme—and extremely serious—case, but scarring and improper regrowth of tissues result from many accidents. If tissues always regrew properly, injury would do no permanent physical damage.

Source:
>1991 "Nanomedicine," Chapter 10, Unbounding the Future (K. Eric Drexler, Christine Peterson, Gayle Pergamit)
>Dec. 1994 "Nanotechnology and Medicine" (Ralph C. Merkle)

Nanotechnology Revolution(1)

2009-06-08T20:53:00.000-07:00

Our bodies are filled with intricate, active molecular structures. When those structures are damaged, health suffers. Modern medicine can affect the workings of the body in many ways, but from a molecular viewpoint it remains crude indeed. Molecular manufacturing can construct a range of medical instruments and devices with far greater abilities. The body is an enormously complex world of molecules. With nanotechnology to help, we can learn to repair it.
The Molecular Body
To understand what nanotechnology can do for medicine, we need a picture of the body from a molecular perspective. The human body can be seen as a workyard, construction site, and battleground for molecular machines. It works remarkably well, using systems so complex that medical science still doesn't understand many of them. Failures, though, are all too common.
The Body As Workyard
Molecular machines do the daily work of the body. When we chew and swallow, muscles drive our motions. Muscle fibers contain bundles of molecular fibers that shorten by sliding past one another.
In the stomach and intestines, the molecular machines we call digestive enzymes break down the complex molecules in foods, forming smaller molecules for use as fuel or as building blocks. Molecular devices in the lining of the digestive tract carry useful molecules to the bloodstream.
Meanwhile, in the lungs, molecular storage devices called hemoglobin molecules pick up oxygen. Driven by molecular fibers, the heart pumps blood laden with fuel and oxygen to cells. In the muscles, fuel and oxygen drive contraction based on sliding molecular fibers. In the brain, they drive the molecular pumps that charge nerve cells for action. In the liver, they drive molecular machines that build and break down a whole host of molecules. And so the story continues through all the work of the body.
Yet each of these functions sometimes fails, whether through damage or inborn defect.

Source:
>1991 "Nanomedicine," Chapter 10, Unbounding the Future (K. Eric Drexler, Christine Peterson, Gayle Pergamit)
>Dec. 1994 "Nanotechnology and Medicine" (Ralph C. Merkle)
>http://inventors.about.com/gi/dynamic/offsite.htm?zi=1/XJ/Ya&sdn=inventors&zu=http%3A%2F%2Fen.wikipedia.org%2Fwiki%2FNanotechnology

Age of Convergence

2009-06-08T20:05:00.000-07:00

Nanomedicine is the medical application of nanotechnology. It covers areas such as nanoparticle drug delivery and possible future applications of molecular nanotechnology (MNT) and nanovaccinology. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials Nanomedicine research is directly funded, with the US National Institutes of Health in 2005 funding a five-year plan to set up four nanomedicine centers. In April 2006, the journal Nature Materials estimated that 130 nanotech-based drugs and delivery systems were being developed worldwide
In the near future, advancement in nanomedicine will deliver a valuable set of research tools and clinically helpful devices. The National Nanotechnology Initiative expects new commercial applications in the pharmaceutical industry that will include advanced drug delivery systems, new therapies, and in vivo imaging. The most important innovations are taking place in drug delivery which involves developing nanoscale particles or molecules to improve bioavailability. Bioavailability refers to the presence of drug molecules where they are needed in the body and where they will do the most good. Drug delivery focuses on maximizing bioavailability both at specific places in the body and over a period of time. Over 65 billion dollars is wasted every year because of poor bioavailability. In vivo imaging is another area where tools and devices are being developed. Using nanoparticle contrast agents, images such as ultrasound and MRI have a favorable distribution and improved contrast. The new therapies and surgeries that are being developed might be effective in treating illnesses and diseases such as cancer. Finally, a shift from the possible to the potential will be made when nanorobots such as neuro-electronic interfaces and cell repair machines are discussed. Drug delivery systems, lipid- or polymer-based nanoparticles, can be designed to improve the pharmacological and therapeutic properties of drugs. The strength of drug delivery systems is their ability to alter the pharmacokinetics and biodistribution of the drug. Nanoparticles have unusual properties that can be used to improve drug delivery. Where larger particles would have been cleared from the body, cells take up these nanoparticles because of their size. Complex drug delivery mechanisms are being developed, including the ability to get drugs through cell walls and into cells. Efficiency is important because many diseases depend upon processes within the cell and can only be impeded by drugs that make their way into the cell. Triggered response is one way for drug molecules to be used more efficiently. Drugs are placed in the body and only activate on encountering a particular signal. For example, a drug with poor solubility will be replaced by a drug delivery system where both hydrophilic and hydrophobic environments exist, improving the solubility. Also, a drug may cause tissue damage, but with drug delivery, regulated drug release can eliminate the problem. If a drug is cleared too quickly from the body, this could force a patient to use high doses, but with drug delivery systems clearance can be reduced by altering the pharmacokinetics of the drug. Poor biodistribution is a problem that can affect normal tissues through widespread distribution, but the particulates from drug delivery systems lower the volume of distribution and reduce the effect on non-target tissue. Potential nanodrugs will work by very specific and well-understood mechanisms, one of the major impacts of nanotechnology and nanoscience will be in leading development of completely new drugs with more useful behavior and less side effects.

Biomarker

2009-06-08T19:59:00.000-07:00

Biomarker discovery is the process by which biomarkers are discovered. It is a medical term. Many commonly used blood tests in medicine are biomarkers. The way that these tests have been found can be seen as biomarker discovery. However, their identification has mostly been a one-at-a time approach. Many of these well-known tests have been identified based on clear biological insight, from physiology or biochemistry. This means that only a few markers at a time have been considered. One example of this way of biomarker discovery is the use of injections of inulin for measuring kidney function. From this, one discovered a naturally occurring molecule, creatinine, that enabled the same measurements to be made easily without injections. This can be seen as a serial process.
The recent interest in biomarker discovery is because new molecular biologic techniques promise to find relevant markers rapidly, without detailed insight into mechanisms of disease. By screening many possible biomolecules at a time, a parallel approach can be tried. Genomics and proteomics are some technologies that are used in this process. Significant technical difficulties remain. There is considerable interest in biomarker discovery from the pharmaceutical industry. Blood test or other biomarkers could serve as intermediate markers of disease in clinical trials, and also be possible drug targets.

Source:>http://bioinformations.info/nano-bioengineering.html

Intro Nanotechnology

2009-06-08T19:50:00.000-07:00

Introduction to Nanotechnology
Nanotechnology definition and basic terms.
By Mary Bellis, About.com

Nanotechnology is the application of scientific and engineering principles to make and utilize very small things. The inventions being created based on the new science of nanotechnology promise to make what was science fiction become science fact.

Nanoscience & Nanoengineering
Nanotechnology does not have to be as small as atoms or molecules, but it is much smaller than anything you can see with your naked eye. Many materials exhibit unusual and useful properties when their size is reduced. Researchers who try to understand the fundamentals of these size-dependent properties call their work nanoscience, while those focusing on how to effectively use the properties call their work nanoengineering.

Nanoscale & Nanometer
How do we measure the size of nanotechnology materials? We measure materials using the nanoscale. While not precisely defined, the nanoscale ranges from about 1 nanometer (nm) to 100 nanometers. From things the size of individual atoms on the smallest to what you might see with very good optical microscope at the largest size.A nanometer is one billionth of a meter. (A meter is about 10% longer than a yard.) The prefix “nano” means “one billionth”, or 10-9, in the international system for units of weights and measure. A sheet of paper is about 100,000 nanometers thick; a single gold atom is about a third or a nanometer in diameter.

Nanomaterials
By nanomaterials is a term that refers to all nanosized materials.When particles are purposefully manufactured with nanoscale dimensions, we call them engineered nanoparticles. There are two other ways nanoparticles are formed. Nanoparticles can occur as a byproduct of combustion, industrial manufacturing, and other human activities; these are known as incidental nanoparticles. Natural processes, such as sea spray and erosion, can also create nanoparticles.
Many important functions of living organisms take place at the nanoscale. The human body uses natural nanoscale materials, such as proteins and other molecules, to control the body’s many systems and processes. A typical protein such as hemoglobin, which carries oxygen through the bloodstream, is 5 nms in diameter.
Nanoparticles, Nanotubes, & NanofilmsThink of these simply as particles, tubes, and films that have one or more nanosized dimension. Nanoparticles are bits of a material in which all three dimensions of the particle are within the nanoscale. Nanotubes have a diameter that’s nanosize, but can be several hundred nanometers (nm) long or even longer. Nanofilms or nanoplates have a thickness that’s nanosize, but their other two dimensions can be quite large.

Nanotechnology

2009-06-08T19:47:00.000-07:00

From Wikipedia, the free encyclopedia

Nanotechnology, shortened to "Nanotech", is the study of the control of matter on an atomic and molecular scale. Generally nanotechnology deals with structures of the size 100 nanometers or smaller, and involves developing materials or devices within that size. Nanotechnology is very diverse, ranging from novel extensions of conventional device physics, to completely new approaches based upon molecular self-assembly, to developing new materials with dimensions on the nanoscale, even to speculation on whether we can directly control matter on the atomic scale.
There has been much debate on the future of implications of nanotechnology. Nanotechnology has the potential to create many new materials and devices with wide-ranging applications, such as in medicine, electronics, and energy production. On the other hand, nanotechnology raises many of the same issues as with any introduction of new technology, including concerns about the toxicity and environmental impact of nanomaterials [1], and their potential effects on global economics, as well as speculation about various doomsday scenarios. These concerns have led to a debate among advocacy groups and governments on whether special regulation of nanotechnology is warranted.

Biomedical Engineering

2009-06-08T19:35:00.000-07:00

Definition of Biomedical Engineering
Biomedical engineering is a discipline that advances knowledge in engineering, biology and medicine, and improves human health through cross-disciplinary activities that integrate the engineering sciences with the biomedical sciences and clinical practice. It includes:
1. The acquisition of new knowledge and understanding of living systems through the innovative and substantive application of experimental and analytical techniques based on the engineering sciences.
2. The development of new devices, algorithms, processes and systems that advance biology and medicine and improve medical practice and health care delivery.As used by the foundation, the term "biomedical engineering research" is thus defined in a broad sense: It includes not only the relevant applications of engineering to medicine but also to the basic life sciences."

>Source:http://www.bmes.org/WhitakerArchives/glance/definition.html

As can be seen from the definition biomedical engineering is a wide open field that historically attempts to advance and apply engineering knowledge that will lead to new or improve current medical technology. As the term "medical" suggests the vast majority of this research focuses on technology that helps improve human health.If you decide to delve into this field it will be useful to know some context and definitions which can be found below.

>http://en.wikipedia.org/wiki/Bioengineer
>http://www.bmes.org/WhitakerArchives/glance/history.html
>More Informations

Nanomedicine FAQ(7)

2009-06-08T19:17:00.000-07:00

The following nanomedicine FAQ and their answers have been compiled by Robert A. Freitas Jr.
7. How would the nanorobots be retrieved from the body?Some nanodevices will be able to exfuse themselves from the body via the usual human excretory channels; others will be designed to allow ready exfusion by medical personnel using apheresis-like processes (commonly called nanapheresis) or active scavenger systems. It is very design dependent. In the case of the respirocytes, the removal procedure is fairly simple:
"Once a therapeutic purpose is completed, it may be desirable to extract artificial devices from circulation. Onboard water ballast control is extremely useful during respirocyte exfusion from the blood. Blood to be cleared may be passed from the patient to a specialized centrifugation apparatus where acoustic transmitters command respirocytes to establish neutral buoyancy. No other solid blood component can maintain exact neutral buoyancy, hence those other components precipitate outward during gentle centrifugation and are drawn off and added back to filtered plasma on the other side of the apparatus. Meanwhile, after a period of centrifugation, the plasma, containing mostly suspended respirocytes but few other solids, is drawn off through a 1-micron filter, removing the respirocytes. Filtered plasma is recombined with centrifuged solid components and returned undamaged to the patient's body. The rate of separation is further enhanced either by commanding respirocytes to empty all tanks, lowering net density to 66% of blood plasma density, or by commanding respirocytes to blow a 5-micron O2 gas bubble to which the device may adhere via surface tension, allowing it to rise at 45 mm/hour under normal gravitational acceleration."
(Quoted from Robert A. Freitas Jr., "Exploratory Design in Medical Nanotechnology: A Mechanical Artificial Red Cell," Artificial Cells, Volume 26, 1998, pp. 411-430. This paper is apparently the first detailed design study of a specific medical nanodevice (of the general type proposed by Drexler in Nanosystems) that has been published. See earlier description in: Robert A. Freitas Jr., "Respirocytes: High Performance Artificial Nanotechnology Red Blood Cells," Nanotechnology Magazine, Volume 2, October 1996, pp. 1, 8-13.)

Nanomedicine FAQ(6)

2009-06-08T19:12:00.000-07:00

The following nanomedicine FAQ and their answers have been compiled by Robert A. Freitas Jr.
6. Will "old nanorobots" left in the body cause problems when they eventually fail?Following most simple treatments, nanodoctors of the 21st century will want to remove their therapeutic nanorobots from the patient's body as soon as the nanodevices have finished the job. So there will be little danger of "old nanorobots" breaking down or malfunctioning, or causing something unpleasant to happen to the patient after the original disease or traumatic condition has been treated.
Additionally, nanorobots will be designed with a high level of redundancy to ensure fail-operational and fail-safe performance, further reducing the medical risk.

Nanomedicine FAQ(5)

2009-06-08T19:11:00.000-07:00

The following nanomedicine FAQ and their answers have been compiled by Robert A. Freitas Jr.
5. Can you give a concrete example of a simple medical nanorobot?One very simple nanorobot that I designed a few years ago is the artificial mechanical red cell, which I call a "respirocyte." The respirocyte measures about 1 micron in diameter and just floats along in the bloodstream. It is a spherical nanorobot made of 18 billion atoms. These atoms are mostly carbon atoms arranged as diamond in a porous lattice structure inside the spherical shell. The respirocyte is essentially a tiny pressure tank that can be pumped full of up to 9 billion oxygen (O2) and carbon dioxide (CO2) molecules. Later on, these gases can be released from the tiny tank in a controlled manner. The gases are stored onboard at pressures up to about 1000 atmospheres. (Respirocytes can be rendered completely nonflammable by constructing the device internally of sapphire, a flameproof material with chemical and mechanical properties otherwise similar to diamond.)
The surface of each respirocyte is 37% covered with 29,160 molecular sorting rotors (Nanosystems, page 374) that can load and unload gases into the tanks. There are also gas concentration sensors on the outside of each device. When the nanorobot passes through the lung capillaries, O2 partial pressure is high and CO2 partial pressure is low, so the onboard computer tells the sorting rotors to load the tanks with oxygen and to dump the CO2. When the device later finds itself in the oxygen-starved peripheral tissues, the sensor readings are reversed. That is, CO2 partial pressure is relatively high and O2 partial pressure relatively low, so the onboard computer commands the sorting rotors to release O2 and to absorb CO2.
Respirocytes mimic the action of the natural hemoglobin-filled red blood cells. But a respirocyte can deliver 236 times more oxygen per unit volume than a natural red cell. This nanorobot is far more efficient than biology, mainly because its diamondoid construction permits a much higher operating pressure. (The operating pressure of the natural red blood cell is the equivalent of only about 0.51 atm, of which only about 0.13 atm is deliverable to tissues.) So the injection of a 5 cm3 dose of 50% respirocyte aqueous suspension into the bloodstream can exactly replace the entire O2 and CO2 carrying capacity of the patient's entire 5,400 cm3 of blood!
Respirocytes will have pressure sensors to receive acoustic signals from the doctor, who will use an ultrasound-like transmitter device to give the respirocytes commands to modify their behavior while they are still inside the patient's body. For example, the doctor might order all the respirocytes to just stop pumping, and become dormant. Later, the doctor might order them all to turn on again.
What if you added 1 liter of respirocytes into your bloodstream, the maximum that could possibly be safe? You could then hold your breath for nearly 4 hours if sitting quietly at the bottom of a swimming pool. Or if you were sprinting at top speed, you could run for at least 15 minutes before you had to take a breath!
It is clear that very "simple" medical nanodevices can have extremely useful abilities, even when applied in relatively small doses. Other more complex devices will have a broader range of capabilities. Some devices may have mobilitythe ability to swim through the blood, or crawl through body tissue or along the walls of arteries. Others will have different shapes, colors, and surface textures, depending on the functions they must perform. They will have different types of robotic manipulators, different sensor arrays, and so forth. Each medical nanorobot will be designed to do a particular job extremely well, and will have a unique shape and behavior.

Nanomedicine FAQ(4)

2009-06-08T19:09:00.000-07:00

The following nanomedicine FAQ and their answers have been compiled by Robert A. Freitas Jr.
4. What would a typical nanorobot look like?It is impossible to say exactly what a generic nanorobot would look like. Nanorobots intended to travel through the bloodstream to their target will probably be 500-3000 nanometers (1 nanometer = 10-9 meter) in characteristic dimension. Nonbloodborne tissue-traversing nanorobots might be as large as 50-100 microns, and alimentary or bronchial-traveling nanorobots may be even larger still. Each species of medical nanorobot will be designed to accomplish a specific task, and many shapes and sizes are possible.
Finally, and perhaps most importantly, no actual working nanorobot has yet been built. Many theoretical designs have been proposed that look good on paper, but these preliminary designs could change significantly after the necessary research, development and testing has been completed.

Nanomedicine FAQ(3)

2009-06-08T18:55:00.000-07:00

The following nanomedicine FAQ and their answers have been compiled by Robert A. Freitas Jr.
3. What would be the physical appearance of a human who has been injected with medical nanorobots?In most cases a human patient who is is undergoing a nanomedical treatment is going to look just like anyone else who is sick. The typical nanomedical treatment (e.g. to combat a bacterial or viral infection) will consist of an injection of perhaps a few cubic centimeters of micron-sized nanorobots suspended in fluid (probably a water/saline suspension). The typical therapeutic dose may include up to 1-10 trillion (1 trillion = 1012) individual nanorobots, although in some cases treatment may only require a few million or a few billion individual devices to be injected. Each nanorobot will be on the order of perhaps 0.5 micron up to perhaps 3 microns in diameter. (The exact size depends on the design, and on exactly what the nanorobots are intended to do.)
The adult human body has a volume of perhaps 100,000 cm3 and a blood volume of ~5400 cm3, so adding a mere ~3 cm3 dose of nanorobots is not particularly invasive. The nanorobots are going to be doing exactly what the doctor tells them to do, and nothing more (barring malfunctions). So the only physical change you will see in the patient is that he or she will very rapidly become well again. Most symptoms such as fever and itching have specific biochemical causes which can also be managed, reduced, and eliminated using the appropriate injected nanorobots. Major rashes or lesions such as those that occur when you have the measles will take a bit longer to reverse, because in this case the broken skin must also be repaired.

Nanomedicine FAQ(2)

2009-06-08T18:54:00.000-07:00

The following nanomedicine FAQ and their answers have been compiled by Robert A. Freitas Jr.
2. Could human body fluids get inside the nanorobot?From a medical standpoint, it makes sense to regard the nanorobot as having two spaces which should be considered separatelyits interior and its exterior. It is true that the nanorobot exterior will be exposed to the diverse chemical brew that makes up our human biochemistry. But the interior of the nanorobot may be a highly controlled environment, possibly a vacuum, into which external liquids cannot normally intrude.
Of course it may often be necessary for a nanorobot to import external fluids in a controlled manner for chemical analysis or other purposes. But the important thing is that the device will be watertight and airtight. Body fluids cannot get into the interior of the device, unless these fluids are purposely pumped in for some specific reason.

Nanomedicine FAQ(1)

2009-06-08T18:50:00.000-07:00

The following nanomedicine FAQ and their answers have been compiled by Robert A. Freitas Jr.
1. What chemical elements would medical nanorobots be made of?

The typical medical nanodevice will probably be a micron-scale robot assembled from nanoscale parts. These parts could range in size from 1-100 nm (1 nm = 10-9 meter), and might be fitted together to make a working machine measuring perhaps 0.5-3 microns (1 micron = 10-6 meter) in diameter. Three microns is about the maximum size for bloodborne medical nanorobots, due to the capillary passage requirement.
Carbon will likely be the principal element comprising the bulk of a medical nanorobot, probably in the form of diamond or diamondoid/fullerene nanocompositeslargely because of the tremendous strength and chemical inertness of diamond. Many other light elements such as hydrogen, sulfur, oxygen, nitrogen, fluorine, silicon, etc. will be used for special purposes in nanoscale gears and other components.

Biomedical Nanotechnology

2009-06-08T07:47:00.000-07:00

Biomedical nanotechnology is one of the fastest-growing fields of research across the globe. However, even the most promising technologies may never realize their full potential if public and political opinions are galvanized against them, a situation clearly evident in such controversial fields as cloning and stem cell research. Biomedical Nanotechnology presents state-of-the-art research in the field and also considers the socio-political risks and perceptions of this important science. Contributed by prominent experts in this expansive and interdisciplinary field, Biomedical Nanotechnology examines developments in three sub-fields: nanodrugs and drug delivery; prostheses and implants; and diagnostics and screening technologies. The authors compare new capabilities introduced by nanotechnology to traditional methods of release, target, and controlled drug delivery in the body. They also consider the challenge of understanding and controlling the biological processes involved upon implantation and discuss nanoscale sensors for biological chemical detection and biodefense. The book concludes with individual chapters devoted to the social and economic context of nanotechnologies and to their potential risks and possible solutions. By outlining cutting-edge research in the context of pressing global medical needs and potential risks, this authoritative reference supplies a holistic treatment of biomedical nanotechnology that enables us to understand its implications and decide the best way to move forward.