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Public ETP Nanomedicine

Workshop organized by the Ecole Polytechnique Fdrale de Lausanne (EPFL) and Vision Dyamics, in conjunction with the CMi annual review meeting at EPFL, 8 May 2018 at the Rolex Learning Center (RLC) at EPFL.

ETPN2018, the 13th annual meeting of the European Technology Platform on Nanomedicine, will be held in Berlin on May 28-30 2018. Three days to bring the European Nanomedicine community together!

International conference of Nanotechnologies and Bionanoscience in Heraklion, Crete.

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Public ETP Nanomedicine

Nanomedicine | NEJM

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Regenerative Nanomedicine Lab – yimlab.com

Our recent research article “In-vitro Topographical Model of Fuchs Dystrophy for Evaluation of Corneal Endothelial Cell Monolayer Formation” appeared on theBack cover of Advanced Healthcare Materials latest issue.

Several diseases have been known to be caused by microstructural changes in the extracellular microenvironment. Therefore, the knowledge of the interaction of cells with the altered extracellular micro-structures or surface topography is critical to develop a better understanding of the disease for therapeutic development. One such disease is Fuchs corneal endothelial dystrophy (FED). FED is the primary disease and major reason of corneal endothelial cell death. If left untreated, corneal blindness will be resulted; thus, FED is the leading indication for corneal transplantation. In the USA, 4% of population over the age of 40 is believed to have compromised corneal endothelium due to FED, which will further increase due to increasing life expectancy and rapidly ageing population. A diagnostic clinical hallmark of FED is the development of discrete pillar or dome-like microstructures on the corneal endothelial basement membrane (Descemet membrane). These microstructures are called corneal guttata or guttae. Cell therapies have been proposed as an alternative treatment method for Fuchs dystrophy patients. However, currently, no in-vitro or in-vivo FED disease model is available to study the cell therapies before clinical trials.

In this study, the pathological changes in the micro-structure of basement membranes resulting from FED disease was analyzed, to identify geometrical dimension to develop an in-vitro disease model of synthetic corneal guttata pillars/domes by using microfabrication techniques. This model was used to study the monolayer formation of donor-derived human corneal endothelial cells to test the effectiveness of the corneal endothelial cell regenerative therapies. The results suggest that the corneal cell therapies may not be equally effective for patients at different stages of disease progression. The pre-existing guttata in patients could interfere with the cells thus hampering monolayer formation within the eye. Surgical removal of the guttata from the diseased Descemet membrane prior to cell regenerative therapy could increase the success rate of monolayer formation, which could potentially increase the chances of cell therapy success. This study also demonstrate how biomaterial design can be employed to mimic the pathological microstructural changes in basement membranes for better understanding of cellular responses in disease conditions.

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Regenerative Nanomedicine Lab – yimlab.com

Nanomedicine | NEJM

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Nanomedicine | NEJM

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Nanomedicine: Nanotechnology, Biology and Medicine, In Press

Note to users: The section “Articles in Press” contains peer reviewed and accepted articles to be published in this journal. When the final article is assigned to an issue of the journal, the “Article in Press” version will be removed from this section and will appear in the associated journal issue.

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Nanomedicine: Nanotechnology, Biology and Medicine, In Press

Nanomedicine | NEJM

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Public ETP Nanomedicine

The INTERNATIONAL SCHOOL OF NANOMEDICINE has the pleasure to invite you to attend the course Nanofluidics, Nanoimaging and Nanomanipulation that will be held on 5-11 April 2018 at International ETTORE MAJORANA FOUNDATION AND CENTRE FOR SCIENTIFIC CULTURE of ERICE (Sicily) Italy.

Workshop organized by the Ecole Polytechnique Fdrale de Lausanne (EPFL) and Vision Dyamics, in conjunction with the CMi annual review meeting at EPFL, 8 May 2018 at the Rolex Learning Center (RLC) at EPFL.

ETPN2018, the 13th annual meeting of the European Technology Platform on Nanomedicine, will be held in Berlin on May 28-30 2018. Three days to bring the European Nanomedicine community together!

International conference of Nanotechnologies and Bionanoscience in Heraklion, Crete.

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Public ETP Nanomedicine

Nanomedicine | NEJM

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Nanomedicine | NEJM

Nanomedicine Lab

In Vivo Reprogramming in Regenerative Medicine, originally published: 21 November 2017, 83-98

In Vivo Reprogramming in Regenerative Medicine, originally published: 21 November 2017, 65-82

ACS Nano, 2018, in press

Chem, 2018, in press

Nanoscale, 2018, in press

Science Robotics, 2017, 2, 12, eaaq1155

Nanoscale, 2017, in press

Advanced Healthcare Materials, 2017, in press

2D Materials, 2017, in press

npj 2D Materials and Applications, 2017, in press

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Nanomedicine Lab

Public ETP Nanomedicine

The INTERNATIONAL SCHOOL OF NANOMEDICINE has the pleasure to invite you to attend the course Nanofluidics, Nanoimaging and Nanomanipulation that will be held on 5-11 April 2018 at International ETTORE MAJORANA FOUNDATION AND CENTRE FOR SCIENTIFIC CULTURE of ERICE (Sicily) Italy.

Workshop organized by the Ecole Polytechnique Fdrale de Lausanne (EPFL) and Vision Dyamics, in conjunction with the CMi annual review meeting at EPFL, 8 May 2018 at the Rolex Learning Center (RLC) at EPFL.

ETPN2018, the 13th annual meeting of the European Technology Platform on Nanomedicine, will be held in Berlin on May 28-30 2018. Three days to bring the European Nanomedicine community together!

International conference of Nanotechnologies and Bionanoscience in Heraklion, Crete.

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Public ETP Nanomedicine

Nanomedicine | NEJM

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Nanomedicine – Wikipedia

Nanomedicine is the medical application of nanotechnology.[1] Nanomedicine ranges from the medical applications of nanomaterials and biological devices, to nanoelectronic biosensors, and even possible future applications of molecular nanotechnology such as biological machines. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials (materials whose structure is on the scale of nanometers, i.e. billionths of a meter).

Functionalities can be added to nanomaterials by interfacing them with biological molecules or structures. The size of nanomaterials is similar to that of most biological molecules and structures; therefore, nanomaterials can be useful for both in vivo and in vitro biomedical research and applications. Thus far, the integration of nanomaterials with biology has led to the development of diagnostic devices, contrast agents, analytical tools, physical therapy applications, and drug delivery vehicles.

Nanomedicine seeks to deliver a valuable set of research tools and clinically useful devices in the near future.[2][3] 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.[4] Nanomedicine research is receiving funding from the US National Institutes of Health Common Fund program, supporting four nanomedicine development centers.[5]

Nanomedicine sales reached $16 billion in 2015, with a minimum of $3.8 billion in nanotechnology R&D being invested every year. Global funding for emerging nanotechnology increased by 45% per year in recent years, with product sales exceeding $1 trillion in 2013.[6] As the nanomedicine industry continues to grow, it is expected to have a significant impact on the economy.

Nanotechnology has provided the possibility of delivering drugs to specific cells using nanoparticles.[7] The overall drug consumption and side-effects may be lowered significantly by depositing the active agent in the morbid region only and in no higher dose than needed. Targeted drug delivery is intended to reduce the side effects of drugs with concomitant decreases in consumption and treatment expenses. Drug delivery focuses on maximizing bioavailability both at specific places in the body and over a period of time. This can potentially be achieved by molecular targeting by nanoengineered devices.[8][9] A benefit of using nanoscale for medical technologies is that smaller devices are less invasive and can possibly be implanted inside the body, plus biochemical reaction times are much shorter. These devices are faster and more sensitive than typical drug delivery.[10] The efficacy of drug delivery through nanomedicine is largely based upon: a) efficient encapsulation of the drugs, b) successful delivery of drug to the targeted region of the body, and c) successful release of the drug.[citation needed]

Drug delivery systems, lipid-[11] or polymer-based nanoparticles,[12] can be designed to improve the pharmacokinetics and biodistribution of the drug.[13][14][15] However, the pharmacokinetics and pharmacodynamics of nanomedicine is highly variable among different patients.[16] When designed to avoid the body’s defence mechanisms,[17] nanoparticles have beneficial properties that can be used to improve drug delivery. Complex drug delivery mechanisms are being developed, including the ability to get drugs through cell membranes and into cell cytoplasm. 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.[18] Drug delivery systems may also be able to prevent tissue damage through regulated drug release; reduce drug clearance rates; or lower the volume of distribution and reduce the effect on non-target tissue. However, the biodistribution of these nanoparticles is still imperfect due to the complex host’s reactions to nano- and microsized materials[17] and the difficulty in targeting specific organs in the body. Nevertheless, a lot of work is still ongoing to optimize and better understand the potential and limitations of nanoparticulate systems. 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.[19]

Nanoparticles are under research for their potential to decrease antibiotic resistance or for various antimicrobial uses.[20][21][22] Nanoparticles might also used to circumvent multidrug resistance (MDR) mechanisms.[7]

Two forms of nanomedicine that have already been tested in mice and are awaiting human testing will use gold nanoshells to help diagnose and treat cancer,[23] along with liposomes as vaccine adjuvants and drug transport vehicles.[24][25] Similarly, drug detoxification is also another application for nanomedicine which has shown promising results in rats.[26] Advances in Lipid nanotechnology was also instrumental in engineering medical nanodevices and novel drug delivery systems as well as in developing sensing applications.[27] Another example can be found in dendrimers and nanoporous materials. Another example is to use block co-polymers, which form micelles for drug encapsulation.[12]

Polymeric nanoparticles are a competing technology to lipidic (based mainly on Phospholipids) nanoparticles. There is an additional risk of toxicity associated with polymers not widely studied or understood. The major advantages of polymers is stability, lower cost and predictable characterisation. However, in the patient’s body this very stability (slow degradation) is a negative factor. Phospholipids on the other hand are membrane lipids (already present in the body and surrounding each cell), have a GRAS (Generally Recognised As Safe) status from FDA and are derived from natural sources without any complex chemistry involved. They are not metabolised but rather absorbed by the body and the degradation products are themselves nutrients (fats or micronutrients).[citation needed]

Protein and peptides exert multiple biological actions in the human body and they have been identified as showing great promise for treatment of various diseases and disorders. These macromolecules are called biopharmaceuticals. Targeted and/or controlled delivery of these biopharmaceuticals using nanomaterials like nanoparticles[28] and Dendrimers is an emerging field called nanobiopharmaceutics, and these products are called nanobiopharmaceuticals.[citation needed]

Another highly efficient system for microRNA delivery for example are nanoparticles formed by the self-assembly of two different microRNAs deregulated in cancer.[29]

Another vision is based on small electromechanical systems; nanoelectromechanical systems are being investigated for the active release of drugs and sensors. Some potentially important applications include cancer treatment with iron nanoparticles or gold shells or cancer early diagnosis.[30] Nanotechnology is also opening up new opportunities in implantable delivery systems, which are often preferable to the use of injectable drugs, because the latter frequently display first-order kinetics (the blood concentration goes up rapidly, but drops exponentially over time). This rapid rise may cause difficulties with toxicity, and drug efficacy can diminish as the drug concentration falls below the targeted range.[citation needed]

Some nanotechnology-based drugs that are commercially available or in human clinical trials include:

Existing and potential drug nanocarriers have been reviewed.[7][41][42][43][44][45][46]

Nanoparticles have high surface area to volume ratio. This allows for many functional groups to be attached to a nanoparticle, which can seek out and bind to certain tumor cells.[47] 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).[48] Limitations to conventional cancer chemotherapy include drug resistance, lack of selectivity, and lack of solubility.[46] Nanoparticles have the potential to overcome these problems.[41][49]

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, growth and tumors. Kanzius RF therapy is one example of such therapy (nanoparticle hyperthermia) .[citation needed] Also, gold nanoparticles have the potential to join numerous therapeutic functions into a single platform, by targeting specific tumor cells, tissues and organs.[50][51]

In vivo imaging is another area where tools and devices are being developed.[52] Using nanoparticle contrast agents, images such as ultrasound and MRI have a favorable distribution and improved contrast. In cardiovascular imaging, nanoparticles have potential to aid visualization of blood pooling, ischemia, angiogenesis, atherosclerosis, and focal areas where inflammation is present.[52]

The small size of nanoparticles endows them with properties that can be very useful in oncology, particularly in imaging.[7] 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. 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.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, but this concern may be addressed by use of fluorescent dopants.[53]

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.[53] 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. They have also found a way to insert nanoparticles[54] into the affected parts of the body so that those parts of the body will glow showing the tumor growth or shrinkage or also organ trouble.[55]

Nanotechnology-on-a-chip is one more dimension of lab-on-a-chip technology. Magnetic nanoparticles, bound to a suitable antibody, are used to label specific molecules, structures or microorganisms. In particular silica nanoparticles are inert from the photophysical point of view and might accumulate a large number of dye(s) within the nanoparticle shell.[28] Gold nanoparticles tagged with short segments of DNA can be used for detection of genetic sequence in a sample. Multicolor optical coding for biological assays has been achieved by embedding different-sized quantum dots into polymeric microbeads. Nanopore technology for analysis of nucleic acids converts strings of nucleotides directly into electronic signatures.[citation needed]

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.[56] Nanotechnology is helping to advance the use of arthroscopes, which are pencil-sized devices that are used in surgeries with lights and cameras so surgeons can do the surgeries with smaller incisions. The smaller the incisions the faster the healing time which is better for the patients. It is also helping to find a way to make an arthroscope smaller than a strand of hair.[57]

Research on nanoelectronics-based cancer diagnostics could lead to tests that can be done in pharmacies. The results promise to be highly accurate and the product promises to be inexpensive. They could take a very small amount of blood and detect cancer anywhere in the body in about five minutes, with a sensitivity that is a thousand times better than in a conventional laboratory test. These devices that are built with nanowires to detect cancer proteins; each nanowire detector is primed to be sensitive to a different cancer marker.[30] The biggest advantage of the nanowire detectors is that they could test for anywhere from ten to one hundred similar medical conditions without adding cost to the testing device.[58] Nanotechnology has also helped to personalize oncology for the detection, diagnosis, and treatment of cancer. It is now able to be tailored to each individuals tumor for better performance. They have found ways that they will be able to target a specific part of the body that is being affected by cancer.[59]

Magnetic micro particles are proven research instruments for the separation of cells and proteins from complex media. The technology is available under the name Magnetic-activated cell sorting or Dynabeads among others. More recently it was shown in animal models that magnetic nanoparticles can be used for the removal of various noxious compounds including toxins, pathogens, and proteins from whole blood in an extracorporeal circuit similar to dialysis.[60][61] In contrast to dialysis, which works on the principle of the size related diffusion of solutes and ultrafiltration of fluid across a semi-permeable membrane, the purification with nanoparticles allows specific targeting of substances. Additionally larger compounds which are commonly not dialyzable can be removed.[citation needed]

The purification process is based on functionalized iron oxide or carbon coated metal nanoparticles with ferromagnetic or superparamagnetic properties.[62] Binding agents such as proteins,[61] antibodies,[60] antibiotics,[63] or synthetic ligands[64] are covalently linked to the particle surface. These binding agents are able to interact with target species forming an agglomerate. Applying an external magnetic field gradient allows exerting a force on the nanoparticles. Hence the particles can be separated from the bulk fluid, thereby cleaning it from the contaminants.[65][66]

The small size (

This approach offers new therapeutic possibilities for the treatment of systemic infections such as sepsis by directly removing the pathogen. It can also be used to selectively remove cytokines or endotoxins[63] or for the dialysis of compounds which are not accessible by traditional dialysis methods. However the technology is still in a preclinical phase and first clinical trials are not expected before 2017.[68]

Nanotechnology may be used as part of tissue engineering to help reproduce or repair or reshape damaged tissue using suitable nanomaterial-based scaffolds and growth factors. Tissue engineering if successful may replace conventional treatments like organ transplants or artificial implants. Nanoparticles such as graphene, carbon nanotubes, molybdenum disulfide and tungsten disulfide are being used as reinforcing agents to fabricate mechanically strong biodegradable polymeric nanocomposites for bone tissue engineering applications. The addition of these nanoparticles in the polymer matrix at low concentrations (~0.2 weight%) leads to significant improvements in the compressive and flexural mechanical properties of polymeric nanocomposites.[69][70] Potentially, these nanocomposites may be used as a novel, mechanically strong, light weight composite as bone implants.[citation needed]

For example, a flesh welder was demonstrated to fuse two pieces of chicken meat into a single piece using a suspension of gold-coated nanoshells activated by an infrared laser. This could be used to weld arteries during surgery.[71] Another example is nanonephrology, the use of nanomedicine on the kidney.

Neuro-electronic interfacing is 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. A refuelable strategy implies energy is refilled continuously or periodically with external sonic, chemical, tethered, magnetic, or biological electrical sources, while a nonrefuelable strategy implies that all power is drawn from internal energy storage which would stop when all energy is drained. A nanoscale enzymatic biofuel cell for self-powered nanodevices have been developed that uses glucose from biofluids including human blood and watermelons.[72] One limitation to this innovation is the fact that electrical interference or leakage or overheating from power consumption is possible. The wiring of the structure is extremely difficult because they must be positioned precisely in the nervous system. The structures that will provide the interface must also be compatible with the body’s immune system.[73]

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. Nanomedicine would make use of these nanorobots, introduced into the body, to repair or detect damages and infections. 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.[1][73][74][75] Future advances in nanomedicine could give rise to life extension through the repair of many processes thought to be responsible for aging. K. Eric Drexler, one of the founders of nanotechnology, postulated cell repair machines, including ones operating within cells and utilizing as yet hypothetical molecular machines, in his 1986 book Engines of Creation, with the first technical discussion of medical nanorobots by Robert Freitas appearing in 1999.[1] Raymond Kurzweil, a futurist and transhumanist, stated in his book The Singularity Is Near that he believes that advanced medical nanorobotics could completely remedy the effects of aging by 2030.[76] According to Richard Feynman, it was his former graduate student and collaborator Albert Hibbs who originally suggested to him (circa 1959) the idea of a medical use for Feynman’s theoretical micromachines (see nanotechnology). Hibbs suggested that certain repair machines might one day be reduced in size to the point that it would, in theory, be possible to (as Feynman put it) “swallow the doctor”. The idea was incorporated into Feynman’s 1959 essay There’s Plenty of Room at the Bottom.[77]

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Nanomedicine – Wikipedia

Nanomedicine Fact Sheet – National Human Genome Research …

NanomedicineOverview

What if doctors had tiny tools that could search out and destroy the very first cancer cells of a tumor developing in the body? What if a cell’s broken part could be removed and replaced with a functioning miniature biological machine? Or what if molecule-sized pumps could be implanted in sick people to deliver life-saving medicines precisely where they are needed? These scenarios may sound unbelievable, but they are the ultimate goals of nanomedicine, a cutting-edge area of biomedical research that seeks to use nanotechnology tools to improve human health.

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A lot of things are small in today’s high-tech world of biomedical tools and therapies. But when it comes to nanomedicine, researchers are talking very, very small. A nanometer is one-billionth of a meter, too small even to be seen with a conventional lab microscope.

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Nanotechnology is the broad scientific field that encompasses nanomedicine. It involves the creation and use of materials and devices at the level of molecules and atoms, which are the parts of matter that combine to make molecules. Non-medical applications of nanotechnology now under development include tiny semiconductor chips made out of strings of single molecules and miniature computers made out of DNA, the material of our genes. Federally supported research in this area, conducted under the rubric of the National Nanotechnology Initiative, is ongoing with coordinated support from several agencies.

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For hundreds of years, microscopes have offered scientists a window inside cells. Researchers have used ever more powerful visualization tools to extensively categorize the parts and sub-parts of cells in vivid detail. Yet, what scientists have not been able to do is to exhaustively inventory cells, cell parts, and molecules within cell parts to answer questions such as, “How many?” “How big?” and “How fast?” Obtaining thorough, reliable measures of quantity is the vital first step of nanomedicine.

As part of the National Institutes of Health (NIH) Common Fund [nihroadmap.nih.gov], the NIH [nih.gov] has established a handful of nanomedicine centers. These centers are staffed by a highly interdisciplinary scientific crew, including biologists, physicians, mathematicians, engineers and computer scientists. Research conducted over the first few years was spent gathering extensive information about how molecular machines are built.

Once researchers had catalogued the interactions between and within molecules, they turned toward using that information to manipulate those molecular machines to treat specific diseases. For example, one center is trying to return at least limited vision to people who have lost their sight. Others are trying to develop treatments for severe neurological disorders, cancer, and a serious blood disorder.

The availability of innovative, body-friendly nanotools that depend on precise knowledge of how the body’s molecular machines work, will help scientists figure out how to build synthetic biological and biochemical devices that can help the cells in our bodies work the way they were meant to, returning the body to a healthier state.

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Last Updated: January 22, 2014

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