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Researchers Explore Possible Applications of Nanotechnology in Cancer Treatmentby Ann Sutton
In his book, Engines of Creation, K. Eric Drexler postulates a world in which tiny robots are unable to control their own self-replication and eventually engulf the earth. Such doomsday scenarios reflect a common misunderstanding about nanotechnology. Most scientists agree that nanorobots will not be developed for many years, if ever. Instead, current research in nanotechnology is focused on nanomaterials, tiny particles of organic and inorganic matter. These particles and their potential uses in the treatment of cancer are being investigated at The University of Texas M. D. Anderson Cancer Center. Specifically, researchers are looking at ways in which nanomaterials might be used to deliver targeted treatments to cancer cells. Nanotechnology refers to materials, devices, and systems created through the manipulation of matter on a nanometric scale and the exploitation of novel phenomena and properties that occurs at that scale. At 1/80,000th the width of a human hair, a nanometer is the length of 10 hydrogen atoms placed end to end. The possible applications of nanotechnology are innumerable, but medicine and computer science are expected to be among the first fields to yield viable products and techniques. Nanotechnology is already in use in a few commercially available products, including sunscreen and wrinkle-free pants. Nanomaterials are created using either a “top-down” or “bottom-up” approach. The top-down approach refers to etching and molding materials into smaller and smaller components and is applicable to computer technology, whereas the bottom-up approach involves assembling structures atom by atom or molecule by molecule and is therefore more suited to medical research. Gravity exerts control over such things as an ant, a person, or a red dwarf star. However, material smaller than a nanometer is governed not by gravity but by the laws of quantum mechanics. Nanomaterials exist between these two worlds, resulting in odd but exploitable behavior. “Nanotechnology is kind of a test-tube wonder in search of an application,” said Michael G. Rosenblum, Ph.D., a professor in the Department of Bioimmunotherapy at M. D. Anderson. Working with such small materials in medicine poses unique problems. Nanoparticles are so small that they can be cleared out of the body before they complete their mission. They also have large surface areas relative to their volumes, which allows for easier manipulation but means that friction can be a problem. Specialized nanoparticles called nanoshells are the focus of a research collaboration between John D. Hazle, Ph.D., chair (ad interim) and associate professor in the Department of Imaging Physics at M. D. Anderson, and engineers at Rice University in Houston. Nanoshells, which are hollow spheres made of silica and sometimes coated with gold, were invented by Naomi Halas, Ph.D., a professor of electrical and computer engineering and chemistry at Rice University. Antibodies can be attached to the surface of nanoshells, causing the shells to target certain cells. Laser light directed onto the shells from outside of the body would cause them to superheat, destroying tumor cells but leaving healthy cells unaffected. This application of nanoshells is especially attractive in the treatment of prostate cancer; the prostate is near the surface of the body and therefore more easily accessible than other tumor sites. “You could theoretically spare most of the gland and just kill the part of the gland that has the tumor cells,” said Dr. Hazle. Coating the shells with gold has distinct advantages; gold colloids have been used in medicine for years and are known to have low toxicity. “It’s very inert, but you can also do the chemistry needed to bind antibodies and other biomolecules to the gold. These nanoshells can mimic gold colloids; the body doesn’t know that they’re shells instead of particles,” said Dr. Hazle.
Dr. Hazle expects that the use of gold nanoshells in tumor ablation will enter clinical trials in three to four years. “What we’re focusing on is the best way to target cells and get them in a high enough concentration to either directly damage all of the surrounding tumor cells with heat or coagulate the microvasculature and starve them [the tumor cells] though a lack of blood and oxygen,” he said. Nanoshells also could be filled with a drug-containing polymer. Heating the shells would cause the polymer to change shape, squeezing out a controlled amount of the drug. “The shells that were activated would either burst or become permeable enough that the drugs would be able to escape into the local environment, so you could do more of a locoregional therapy and get a much higher local tissue concentration of a drug than you would be able to get systemically,” said Dr. Hazle. Physicians have no way to accurately control the release rate of time-release drug implants, and patients who need regular doses of a medication must go to the doctor’s office often to have the drug administered. Using drug-filled nanoshells would allow for a more accurate rate of drug release and for patients to release the drug themselves by heating the implanted particles with an infrared light. Dr. Rosenblum is studying another type of chemotherapeutic drug delivery system by applying nanotechnology’s most famous discovery, buckminsterfullerene, or the buckyball. A nanoparticle composed of 60 carbon atoms in the shape of a soccer ball, the buckyball earned its discoverers, Sir Harold W. Kroto, Ph.D., of the University of Sussex, UK, and Robert F. Curl, Jr., Ph.D., and Richard E. Smalley, Ph.D., both of Rice University, the 1996 Nobel Prize in Chemistry. “We’re trying to put chemotherapeutic agents on the surface of these particles so that they will be active when they are delivered to the target cell,” said Dr. Rosenblum. The current method of attaching drugs directly to antibodies has not been successful because each element in the pair adversely affects the other. A buckyball could carry separately the drug and the antibodies needed to target a particular cell. It also could deliver more than one kind of drug simultaneously. “What these particles will allow us to do is to link these drugs together on the surface of the sphere in a combination that is synergistic, hopefully delivering that combination punch to the target cell with our antibodies,” said Dr. Rosenblum. Dr. Rosenblum’s group is also evaluating whether buckyballs can safely and efficiently deliver radioisotopes to cancer cells. Calculations suggest that, in most cases, the radioisotopes will not escape their carbon cages before they reach the cells. Buckyballs could potentially deliver currently unusable radioisotopes, such as radon and actinium-225, to tumor cells. “It has the potential for holding radioisotopes for which there is no known chelator, that is, no way to link these isotopes to carrier molecules,” said Dr. Rosenblum. Research into these techniques is still confined to the laboratory and, according to Dr. Rosenblum, there is no way to predict when they might be tested in clinical trials. “Before we do it, there’s no way of knowing how it is going to work,” he said. “We don’t even know what the challenges are at this point, but all of the things we are going to find out are going to be new; that’s the interesting part.” For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789. Other articles in OncoLog, July/August 2003 issue:
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