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Nano Weapons Join the Fight Against Cancer

“Nanoshells” and other tools of the ultrasmall realm could improve diagnosis and treatment of tumors.
April 30, 2004

Imagine being treated for cancer with a couple of visits to your doctor. He simply gives you an injection and then a couple of weeks later runs infrared light over your body to activate cancer-killing agents and excise the tumor. Sound like a Ray Bradbury novel? Don’t tell Naomi Halas that. She is the Stanley C. Moore professor of electrical and computer engineering and professor of chemistry at Rice University, and she has more than imagined it-she’s been developing the process since 1997, when she invented miniscule particles with huge therapeutic potential. She calls them nanoshells.

Nanoshells are microscopic concentric spheres with silica cores and gold shells. Gold gives Halas the thermal and optical response her treatment process requires, and the body generates no antibodies against it. By varying the size of the silica core and the thickness of the gold, Halas found she could “tune” the nanoshells to absorb light of different wavelengths. “For cancer treatment,” she says, “infrared proved best because it penetrates the body the furthest.”

In experiments, nanoshells are injected into an animal’s bloodstream, where “targeting” agents applied to them seek out and attach to the surface receptors of cancerous cells. Illumination with infrared light “raises the cells’ temperature to 55 degrees Celsius” and burns away the tumor, she says.

Halas is focusing her research on breast cancer. She hopes nanoshells will prove a viable alternative to chemotherapy, which kills both healthy and diseased cells, resulting in side effects like fatigue and hair loss. Nanoshells, by contrast, kill only cancer cells.

Nanoshells are just one of several intriguing cancer diagnosis and treatment options that nanotechnology is making possible. Miqin Zhang, a materials scientist at the University of Washington in Seattle, is using her own brand of nanoparticles to noninvasively diagnose and treat brain tumors. She calls her creations “smart superparamagnetic nanoparticle conjugates.” When injected into the bloodstream, these particles target tumors’ cell receptors with agents known as ligands.

Zhang’s nanoparticles are made from iron oxide, which becomes especially magnetic when placed in a magnetic field such as those used for magnetic resonance imaging. The particles therefore enhance the signal that tumors emit during an MRI, making them easier to locate at earlier stages of development. But nanoparticles must circulate long enough to locate tumor cells. Zhang found in early trials that they were quickly attacked and neutralized by antibodies called microphages. So she modified them with a polymer coating that resists microphages. Once the nanoparticles find tumors, they release an attached drug called methotrexate, which kills the cell.

The nanoparticles, which are less than 20 nanometers in diameter, must remain separate from another to do their job. “Aggregated nanoparticles become toxic to healthy tissue,” Zhang explains. The particles’ small size and their ability to permeate tissue let them pass through what’s known as the blood-brain barrier and reach brain tumors. Zhang says this is key because “98 percent of cancer drugs cannot do that.”

Zhang’s combination of complementary chemicals obviates the need for biopsies in diagnosis and operations in treatment and aids in early cancer detection. But according to Mauro Ferrari, a professor of biomedical engineering at Ohio State University and a specialist in biomedical applications of nanotechnology, Zhang’s “work can also help us better see the anatomical contours of cancer.” And according to Zhang, determining the contours of a tumor lets doctors “assess whether or not a cancer therapy is effective in humans in a matter of days rather than the current standard of three months.”

Zhang’s research also “gives us information on cancer molecular expression and its time evolution,” Ferrari adds. A crucial problem in cancer research, he explains, is that at different stages of development the receptors of cancer cells have different molecular expression; that’s why early stage cancer cells may readily uptake an effective drug; with later stage cancer cells, uptake of the drug may not be successful. Zhang’s research, he says, may “help us get the right drugs to the right people at the right time.”

Nanotechnology is also supplying new instruments for examining cancer, potentially yielding new insights. Adam T. Woolley, an assistant professor of chemistry and biochemistry at Brigham Young University, has created a method for examining mutations in DNA to determine a person’s genetic predisposition for developing cancer. He uses a technique called atomic force microscopy (AFM), a nanoscale variation on old record players-but with a needle tip only about 10 nanometers across. Woolley first deposits DNA molecules on silicon or mica, the surfaces of which are so flat that the DNA protrudes above them. Then, he explains, he uses AFM “to examine the topography of the DNA to locate the positions of mutations in it.”

“The difference in size between the native and mutated sequences of DNA is extremely small-about a tenth of a nanometer-which is at the limit of what the AFM can see,” says Woolley. So he uses gold nanoparticles of about 10 nanometers to mark the mutations’ positions-this way, AFM can readily see them. Examining the DNA at this level lets Woolley identify whether a double mutation occurs, which can pose a greater genetic cancer risk than a single one. Conventional techniques for looking at chromosomes can’t determine such information. Woolley’s work has great diagnostic potential, says Ferrari; Identifying the genetic markers for cancer might permit prevention before the first tumor cell ever forms.

Because of its practical implications for battling cancer, such research has captured the attention of the scientific community at large. Robert S. Langer, the Kenneth J. Germeshausen Professor of Chemical and Biomedical Engineering at MIT, is particularly impressed by Halas’ nanoshells. “They are a very nice example of applying materials science to important medical problems,” he says, “and they have a lot of exciting potential.” Rick Kenyon, program manager at the breast cancer research program at the Department of Defense, is funding Halas’ research because, he says, nanoshells allow for “earlier detection and earlier destruction of cancer cells-which is exactly what everybody in the cancer field is looking for.”

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