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.
The researchers found that the amplification also worked when they used liposomes–tiny liquid-filled spheres made of fat molecules–instead of iron-oxide nanoparticles. That means the self-amplifying process depends on the peptide, and the researchers could use different nanoparticles for various functions. For instance, the magnetic iron-oxide nanoparticles that they use could be employed for diagnosing cancer in humans, because they are popular MRI image-enhancing agents. Liposomes, on the other hand, could be used to carry cancer drugs. “The novelty here is the self-amplification,” Farokhzad says. “The technology would be applicable to just about any other nanoplatform that we use for tumor targeting, whether for imaging or therapeutic purposes.”
Ruoslahti also plans to test other similar peptides that could cause clotting in much more than 20 percent of the blood vessels to choke off the tumor’s oxygen supply.
Making the technique safe and effective will take a lot more work. When injected into mice, the peptide-coated nanoparticles trigger an immune response, and the liver tries to get rid of them. The researchers currently avoid this by injecting a decoy particle to take the immune system’s attention away from the peptide particles. But to be efficient, “we should be able to engineer a nanoparticle that does what we need it to do without the help of other nanoparticles,” Farokhzad says.
Hayat Onyuksel, a pharmaceutics and bioengineering professor at the University of Illinois at Chicago, says that the main safety challenge would arise from precisely what makes this new work exciting: self-amplification. It would be crucial to localize the nanoparticles inside tumors so that they do not cause clots in the liver, lungs, and other organs, and so that drug-carrying nanoparticles do not accumulate in the organs, she says.
It would also be important to control the clotting that the peptides induce inside tumor blood vessels, Amiji says, because the clots could dislodge from the vessels and enter into the brain, heart, or other areas. “As long as you can keep the clots in the tumor, this is a very elegant concept.”
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