'Smart bomb' nanoparticle strategy impacts metastasis

A new treatment strategy using molecular "smart bombs" to target metastasis with anti-cancer drugs leads to good results using significantly lower doses of toxic chemotherapy, with less collateral damage to surrounding tissue, according to a collaborative team of researchers at the University of California, San Diego. By designing a "nanoparticle" drug delivery system, the UC San Diego team, led by Moores UCSD Cancer Center Director of Translational Research David Cheresh, Ph.D., has identified a way to target chemotherapy to achieve a profound impact on metastasis in pancreatic and kidney cancer in mice.

In a study to be published online the week of July 7 in advance of publication in the Proceedings of the National Academy of Sciences (PNAS), Cheresh, professor and vice chair of pathology, and members of his team report that the nanoparticle carrying a payload of chemotherapy homes in on a protein marker called integrin ανβ3 – found on the surface of certain tumor blood vessels where it is associated with development of new blood vessels and malignant tumor growth.

The team found that the nanoparticle/drug combination didn't have much impact on primary tumors, but stopped pancreatic and kidney cancers from metastasizing throughout the bodies of mice. They showed that a greatly reduced dosage of chemotherapy can achieve the desired effect because the drug selectively targets the specific blood vessels that feed the cancerous lesion and kills the lesion without destroying surrounding tissue. The destruction of healthy tissue is a side-effect when chemotherapy is administered systemically, flooding the body with cancer-killing toxins.

"We were able to establish the desired anti-cancer effect while delivering the drug at levels 15 times below what is needed when the drug is used systemically," said Cheresh. "Even more interesting is that the metastatic lesions were more sensitive to this therapy than the primary tumor."