Nanotechnology in the form of a molecular beacon, quantum-dot semiconductor, and magnetic nanoparticles is being developed at Georgia universities to detect cardiovascular, neurodegenerative, and infectious disease. Georgia is not alone in pushing into nanomedicine. Ohio (see Targeted Nanoparticles for Diapeutics in the Imaging section) and Michigan are also moving quickly into the territory.
Why the intense interest in nanomedicine? The examples of gold-coated silica “nanoshells” that can both detect and destroy cancerous cells, and of naturally occurring nanocapsules called “vaults” being possible delivery vehicles for therapeutic drugs and DNA may be a hint. (By the way, did you know that there is already an American Academy of Nanomedicine, which is about to hold first annual conference?) Also:
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Nanocardiology
Georgia Institute of Technology and Emory University are establishing a research program focused on creating advanced nanotechnologies to analyze plaque formation on the molecular level and detect plaque at its early stages, thus helping to prevent heart attack and stroke. Three types of nanoprobes will be developed to detect plaque and discover its genetic causes. One is a “molecular beacon” — a fluorescent biosensor consisting of a single-stranded DNA fragment four to five nanometers in size — that can seek out and detect specific target genes, fluorescing when it finds a cell with a level of gene expression known to contribute to cardiovascular disease. The second nanoprobe, a quantum-dot semiconductor, can be used as a marker for specific proteins and cells and thus help to understand protein-protein interactions in live cells or to detect diseased cells and the formation of early stage plaques, with dramatic sensitivity. The third type of nanoprobe, magnetic nanoparticles, enable an MRI scan to detect early-stage plaques in patients by targeting specific proteins on the surface of cells. The investigators will also develop ultra-sensitive probes for the free radicals inside cells and biomolecular constructs for molecular imaging and therapeutics. The program will integrate the biomedical engineering strengths of Georgia Tech and the cardiology expertise of Emory University School of Medicine. The Georgia Tech/Emory group also plans to expand biomolecular engineering and nanotechnology to the detection and treatment of other diseases, such as neurodegenerative and infectious diseases. The new Michigan Nanotechnology Institute for Medicine and the Biological Sciences at the University of Michigan will draw on the knowledge and experience of U-M researchers and technical experts working in a wide range of physical and biological sciences, as well as in materials research and biomedical engineering. By making it possible for funding agencies to work through just one academic unit, instead of many schools and colleges, the new institute will facilitate external support for cross-disciplinary research in nanotechnology. US researchers have developed “nanoshells” that can both detect and destroy cancerous cells. The gold-coated silica nanospheres have tunable optical properties (like other materials at nanoscale) so can be designed to scatter and absorb light at particular wavelengths. The scattering “lights up” cancer cells when the nanoshells come into contact with them. The absorption generate heats which then destroys the cancer cells. The scattering and absorption peaks occur in the near-infrared (NIR) region, a double benefit because not only is light penetration through tissue at its best in NIR but also NIR light can be generated from a source outside the body, pass harmlessly through normal tissue, and only heat the nanoshells. The imaging and therapy aspects of the nanoshells have been tested separately in animals and are currently being tested together in a mouse tumor model. Significant advantages claimed for this method over alternatives include the speed and low-cost of NIR optical imaging, the greater biocompatibility of gold nanoparticles compared to other types of optically active nanoparticles, such as quantum dots, and that it can readily be adapted for different types of cancer. One of those alternatives, developed by researchers at Washington University School of Medicine, has proved able to find human melanomas as small as 2 millimeters wide in mice within 30 minutes after an injection of nanoparticles. Their method uses MRI and spherical nanoparticles made of “the metal used to provide contrast in MRI images” [gadolinium, presumably], essentially making the contrast stronger. The nanoparticles can be engineered to be detected with nuclear, CT, and ultrasound scanners, as well as MRI. To destroy their targets, the nanoparticles are loaded with the appropriate drug, though apparently dosage is not known in advance and tumors may not be destroyed, at least with one treatment. The therapy is expected to reach clinical trials in a year or two. Nanocapsules to Take Drugs Through Cell Walls The US National Science Foundation is supporting research into naturally occurring nano-capsules called “vaults” that could be used as delivery vehicles for therapeutic drugs and DNA, among a wide range of other applications. Discovered almost 20 years ago, vaults are “hollow, barrel-like structures that circulate by the tens of thousands in just about every cell of the human body, as well as in the cells of monkeys, rats, frogs, electric rays and even slime molds,” says an NSF news release. It is not at all clear that they serve any useful purpose in nature (mice genetically engineered to be incapable of making vaults “show no ill effects whatsoever”), but they have attributes that human ingenuity can put to practical use. First, they can be engineered – so they could be used as structural elements for nanoscale machines or as components of nanoscale electrical circuits. Second, they can smuggle foreign molecules through cellular membranes and into the cell. This “strongly suggests that in practical applications, vault-encapsulated drugs, DNA strands and other such molecules will be able to interact successfully with cell contents.” A research team plans to create vaults that will hone in on specific cell surface receptors, so that they can be directed to enter only certain types of cells. This would make possible, for example:
University of Liverpool researchers have improved upon a DNA analysis technique called methylation profiling that identifies molecular markers in lung cells that are likely to become cancerous. Their new technique combines the sensitivity of high-powered microscopes with the capability of analyzing many samples at a time, and may lead to early detection of lung cancer is from the identification of early biomarkers in patients who are at risk of developing the disease prior to clinical symptoms. In four to five years, Amphora Discovery hopes its “lab on a chip” will be able to predict the side effects of experimental drugs before they are tested in animals or humans. This would be a huge benefit to pharmaceutical companies, preventing such debacles as Vioxx and Bextra, cutting the cost of getting a drug all the way to clinical trial from an average US$75 million to $3-$4 million, and getting a new drug to market four to five years faster. For two years, the company has used its lab chips to measure inhibition — the shutting down of an enzyme, for example — in 130,000 experimental drugs. The resulting 23 million measurements, recorded in the company’s database, will be used to screen for side effects in experimental drugs. “A couple of years ago QuadraSpec’s technology was science fiction,” begins an article in the Indianapolis Star. What is it? It is a “Bio-CD” — a compact disc biosensor to be on the market in 2006 that can run 1,000 medical tests (e.g., blood sugar content) in less than 30 minutes for only a few cents per test. The machine can tell if specific antigens stick to antibodies attached to the discs. |