By using targeted nanoparticles carrying significantly reduced doses of chemotherapy, researchers have demonstrated the ability to preferentially block the spread of cancer, while largely sparing the surrounding tissues. A series of experiments in animals with forms of pancreatic and kidney cancer showed that the nanotechnology therapy consistently reduced the incidence of metastasis by 90 percent as compared with untreated mice.

The results, reported online July 8 in the Proceedings of the National Academy of Sciences, suggest possible new approaches for inhibiting tumor angiogenesis, the formation of blood vessels that supply tumors with the nutrients needed to grow and spread. Dr. David Cheresh, a participant in the NCI Center of Cancer Nanotechnology Excellence (CCNE) at the University of California, San Diego (UCSD), led the study. Dr. Cheresh leads efforts to develop "smart" nanoparticle platforms at the Center.

"Particularly significant and promising is the fact that tumor metastases were reduced in the treated animals," said Dr. Piotr Grodzinski, program director for the NCI Alliance for Nanotechnology in Cancer.

The research builds upon a discovery made earlier by Dr. Cheresh's group showing that a protein called integrin a?ß3 is often found on growing tumor blood vessels but not on preexisting ones. The lipid-based nanoparticles were designed to attach to the protein receptor and deliver doxorubicin, a chemotherapeutic agent typically delivered systemically but with undesirable toxic side-effects.

By encapsulating and targeting the drug through the use of these nanoparticles, the investigators observed a 15-fold improvement in drug efficacy relative to conventional delivery. While the effect on primary tumors was modest, treatment with the nanoparticles was effective in preventing dissemination of the cancer. The researchers noted that this is a highly significant finding since more than 90 percent of patients with solid tumors die due to metastasis.

Dr. Cheresh noted that the CCNE researchers are continuing their work with collaborators at the Moores UCSD Cancer Center to repeat the doxorubicin experiments with newer agents that target additional pathways involved in angiogenesis.