M ATERIALS AND BIOLOGY ECTION S PECIAL S NEWS Nanotechnology Takes Aim at Cancer The science of extremely small materials is poised to revolutionize cancer A softer touch diagnostics, imaging, and treatment and could finally usher in the long- Cancer treatment has had more than its share awaited era of personalized medicine of hype over the years. Yet despite progress in understanding cancer, its diagnosis and treat- If there is a case to be made for personalized These promises have already set off a ment have remained essentially unchanged medicine, cancer is it. Every year, nearly burgeoning effort to marry nanotechnology for decades, and death rates from the disease 1.4 million Americans are diagnosed with with oncology. Most notably, in 2004, NCI are about what they were in 1950. “If you look the disease; another 600,000 die from it. Yet, launched a $144 million cancer nanotech- at the everyday treatment of cancer, it’s just although cancer is often portrayed as a nology initiative. As the foundation of this like it was 30 years ago with just a couple of monolithic illness, it is anything but. There effort, last month NCI announced $26.3 mil- exceptions,” says Michael Phelps, a cancer are more than 200 types of cancers, each with lion for the first year of funding for seven imaging expert at the University of California, many variants. Some are aggressive, some centers of cancer nanotechnology excellence Los Angeles. Chemotherapy, radiation, and docile; some are easily treated, others are designed to foster interdisciplinary work surgery—the big three of treatments—all almost always fatal. Diagnosing, treating, among chemists, materials scientists, and wreak havoc on healthy cells and tissues as and tracking the progress of therapy for biologists. Europe and Japan are also invest- well as cancerous ones. And the only way to each type of cancer has long tell whether they have worked is to wait to see been a dream among oncologists, whether the cancer reappears. and one that has grown closer “The science in this Nanotechnologists hope to break the log- thanks to parallel revolutions in jam by giving oncologists new tools for track- genomics, proteomics, and cell area is exploding. ing and targeting cell surface receptors and biology. Now a new revolution in other molecules specific to cancer cells. This nanotechnology is pushing per- The cancer community push toward personalized medicine has been sonalized cancer treatment closer really gets this now.” under way for years. For example, the cancer than ever before. drug Herceptin, which homes in on a receptor —Gregory Downing, NCI Nanotechnology’s ability to called Her-2 that is overexpressed in certain shape matter on the scale of mole- cancer cells, is given only to patients whose cules is opening the door to a new generation ing heavily in nano approaches to fighting diagnostic tests show they carry Her-2 positive of diagnostics, imaging agents, and drugs for cancer, although nanotechnology funding cells. Nanotechnologists hope to extend that detecting and treating cancer at its earliest agencies there don’t break out specific pro- approach to numerous diagnostics, imaging stages. But perhaps more important, it is grams for cancer. “It’s fair to say [Europe and agents, and medicines. “Cancer can benefit enabling researchers to combine advances, Japan] are putting in complementary from nanotechnology in essentially every creating nanosized particles that contain drugs amounts of money to the U.S. NCI,” says sector of the cancer enterprise,” Ferrari says. designed to kill tumors, targeting compounds Ruth Duncan, a nanomedicine expert at the designed to home in on malignancies, and Welsh School of Pharmacy in Cardiff, Wales. Raising red flags imaging agents designed to light up even the Companies are also getting in on the act: Advances in diagnostics are already well earliest stage cancers. “The future of oncol- More than a half-dozen nanoparticle-based under way in laboratories around the globe. In ogy—and the opportunity to eliminate the suf- imaging agents and therapeutics are either on the October issue of Nature Biotechnology, , 10 (2005) fering and death due to cancer—will hinge on the market, in clinical trials, or awaiting for example, researchers led by Charles 23 our ability to confront cancer at its molecular clinical trials (see table, p. 1134). Lieber of Harvard University described using level,” says Andrew von Eschenbach, former “The science in this area is exploding,” arrays of silicon-based nanowire devices (see director of the U.S. National Cancer Institute says Gregory Downing, who heads NCI’s figure, above) to electrically detect minute (NCI) in Bethesda, Maryland. Unlike previous Office of Technology and Industrial Rela- levels of marker proteins overexpressed in “revolutions” in the “war” on cancer that raised tions. “The cancer community really gets this cancer cells present in blood serum. The BIOTECHNOLOGY NATURE hopes, nanotechnology “is not just one more now.” Thomas Kipps, a cancer biologist at the sensors were nanowire-based field effect ., tool, it’s an entire field and will pervade every- University of California, San Diego, agrees. transistors (FETs) akin to those in computer ET AL thing in medicine,” says Mauro Ferrari, a “I think there is tremendous potential here,” chips. In FETs, a voltage applied to a tiny cancer nanotechnology expert at Ohio State he says. “I hope it doesn’t just turn out to be “gate” electrode controls the flow of charges University in Columbus. hype. But I don’t think it will.” between two other electrodes. Lieber and CREDIT: G. ZHENG 1132 18 NOVEMBER 2005 VOL 310 SCIENCE www.sciencemag.org Published by AAAS M ATERIALS AND BIOLOGY S <<Sensitive. Nanowire devices can detect cancer with readily identifiable DNA strands. If the inner cadmium-tellurium core surrounded by a PECIAL proteins at femtomolar concentrations. target protein is in a test sample, the protein cadmium-selenium layer and then capped with binds to the antibody on the nanoparticle. Next, an organic compound to make the particles colleagues dotted charge-carrying silicon the researchers add another target-seeking anti- water-soluble. The particles are strong nanowires with monoclonal antibodies body tethered to a magnetic bead. They use a absorbers and emitters of infrared light. When S specific for the cancer proteins. When the magnet to pull the beads—and everything the researchers injected animals with tiny ECTION proteins linked up with the antibodies, the bound to them—away from the rest of the amounts of the quantum dots, lymphatic cells electrical charges of the proteins changed the sample, then identify their target protein by quickly cleared the dots and routed them to the conductance of the silicon nanowires. This sequencing the DNA strands. lymph nodes. As the researchers reported in the change signaled the presence and concentra- Mirkin says that clinical trials of the tech- January 2004 issue of Nature Biotechnology, tion of cancer markers. Lieber’s team made nique are planned for next year and that a they could light up the lymph nodes even devices that detected five cancer protein biotech company that he co-founded called through centimeters of skin simply by shining markers: prostate-specific antigen, PSA- Nanosphere in Northbrook, Illinois, plans to near-infrared light from a halogen lamp. If the alpha 1-antichymotrypsin, carcinoembryonic commercialize diagnostics based on it approach works in humans, it could guide sur- antigen, mucin 1, and telomerase. within 2 years. geons to the lymph nodes of biopsy patients. The devices detected mere The notion of using cadmium- femtomolar concentrations of the based quantum dots in humans target proteins without the fluo- has long come under fire, because rescent labels or complicated Plastic matrix the heavy metal is toxic. As an DNA-amplification procedures alternative, in the 3 August issue most often used to detect minute of the Journal of the American concentrations of biological com- Chemical Society, the researchers pounds. What’s more, the novel reported creating indium-based arrays contained 200 transistors semiconducting dots that also that could be addressed individu- MRI contrast worked for mapping sentinel ally, potentially opening the door agent lymph nodes. These dots contained to detecting scores of cancers by arsenic, another toxin, but the testing a single drop of blood. authors say the dose required to Several other research teams Molecular light up lymph nodes may be small have made similar progress in targets enough to keep the toxicity low. electrically detecting cancer- Infrared light–emitting nano- specific markers using other particles are likely to prove most types of nanodevices. Last year, Photodynamic useful in spotting tumors near the sensitizers for example, researchers led by skin surface. For tissues deep Hua Chen of NASA Ames within the body, many groups are Research Center in Mountain turning to magnetic nanoparticles View, California, reported creat- Cancer cell that can be used as contrast agents Cell membrane ing nanoelectrode arrays capable for magnetic resonance imaging of electrically detecting single (MRI) machines. In May, for mutations in the BRCA1 gene, example, Carola Leuschner, a bio- which has been shown to predis- Triple threat. Multifunctional nanoparticles can combine tumor-seeking chemist at the Pennington Biomed- pose patients to several cancers sensors, imaging agents, and toxins that kill cancer cells. ical Research Center in Baton including breast and ovarian can- Rouge, Louisiana, told attendees of cers. First, the researchers took strands of In sight the Nano Science and Technology Institute DNA complementary to BRCA1 DNA and Researchers are also making quick progress (NSTI) meeting in Anaheim, California, that bound them to electrodes made from carbon in using nanotechnology to spot cancer in its her group has developed iron oxide nano- nanotubes. Then they poured a solution con- earliest stages inside the body.