Biomedical NanoEngineering: 2009

วันพฤหัสบดีที่ 11 มิถุนายน พ.ศ. 2552

Breath analyzer

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

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

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

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

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)

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)

What is nanotechnology?(6)

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)

CNTs are now available commercially in limited quantities. They can be grown by several techniques. However, the selective and uniform production of CNTs with specific dimensions and physical properties is yet to be achieved. The potential similarity in size and shape between CNTs and asbestos fibres has led to concerns about their safety.

What is nanotechnology?(4)

What is nanotechnology?(3)

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)

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)

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

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

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

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

วันพุธที่ 10 มิถุนายน พ.ศ. 2552

Biomedical devices

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)

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

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

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

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

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

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

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

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.

Biomedical NanoEngineering