Tuesday, January 16, 2007

Anticancer Nanoparticles Zero In on Tumors

Specially designed nanoparticles could deliver more imaging agents and drugs, leading to more-effective diagnosis and therapies.

By Prachi Patel-Predd

Fluorescent-tagged peptides attached to the surface of iron oxide nanoparticles show up bright green in an image of a breast cancer tumor in mice. The peptides bind to blood protein clots found in tumor blood vessels, helping the nanoparticles seek out tumors, where they play a role in accumulating more nanoparticles. Credit: PNAS

A new class of nanoparticles that home in on tumors and then attract additional nanoparticles to the site could play an important role in diagnosing and treating cancer, according to researchers at the Burnham Institute for Medical Research, in La Jolla, CA.

Because the nanoparticles increase their own accumulation inside tumors, the nanoparticles could be used to deliver larger quantities of MRI image-enhancing agents or cancer drugs into tumors. "The more particles you get into the tumor, the better images you're going to get, and the better therapeutic effect you're going to get if it's a drug-delivery system," says Erkki Ruoslahti, a professor at the Burnham Institute who led the research.

Ruoslahti and his colleagues demonstrated that when tagged with fluorescent molecules, the nanoparticles made images of breast-cancer tumors in mice three times brighter than they would be if the particles did not self-amplify. Imaging is crucial in diagnosing cancer, and a threefold brightness is a substantial improvement for imaging, Ruoslahti says. The particles also induce blood clotting in 20 percent of the blood vessels inside tumors, a property that could be used to destroy tumors by killing their oxygen flow.

Moreover, the new results, published last week in the Proceedings of the National Academy of Sciences, show that the self-amplifying property could be added to drug-carrying nanoparticles. "If you can get threefold more of drug into tumor, that's a big difference," Ruoslahti says.

Interest in using nanotechnology to detect and cure cancer has surged in recent years. By specifically targeting tumors, nanoparticles show promise in minimizing harm to surrounding tissue and reducing the side effects of invasive cancer treatments such as surgery and chemotherapy. One approach to targeting tumors is to coat the surface of nanoparticles with biological molecules that bind to receptor molecules found only in tumor tissue. This "smart-bomber type technology" is very effective at seeking out tumors, says Mansoor Amiji, a pharmaceutical sciences professor at Northeastern University who specializes in nanomedical technologies.

Ruoslahti's team takes this approach by coating iron-oxide nanoparticles with a special peptide that is attracted to blood protein clots found in the walls of tumor blood vessels. When injected into mice with breast cancer, the nanoparticles seek out tumors and bind to the blood-vessel walls.

But then the nanoparticles go a step further. For reasons the researchers do not yet understand, the particles induce more clotting, which attracts even more nanoparticles so that their numbers build up in the tumors. "The concept of a nanoparticle itself being involved in the recruitment of other nanoparticles to the site of interest is a very clever and novel one," says Omid Farokhzad, an assistant professor at Harvard Medical School.