UCSF Scientists Use Nanotechnology to Increase the Amount of Drug Uptake by Tumor Cells

Several studies have shown that antibody-targeting of drug-laden nanoparticles to cancer cell receptors can significantly enhance antitumor efficacy of the drug cargo. Researchers have assumed that this increase in antitumor activity arises because targeted nanoparticles bind to the outside of tumor cells, increasing the local concentration of drug in the vicinity of the tumor. But new data from investigators at the University of California, San Francisco, shows that antibody targeting actually causes cancer cells to take up the attached nanoparticles, increasing the amount of drug inside tumor cells. John W. Park, MD leads a group that is trying to develop antibody-targeted liposomal nanoparticles for treating cancer. Earlier work from this team had shown that drug-loaded liposomes can effectively deliver anticancer agents to brain tumors, but Park and his colleagues wanted to improve the delivery of drug-loaded liposomes so that they better targeted tumor cells. To do that, the investigators used an antibody that targets the tumor cell-surface protein HER2. They then dosed animals bearing HER2-overexpressing breast tumors with these targeted nanoparticles. Data from this study showed that the antibody-targeted liposomes were no better at increasing the amount of drug that reached tumors. However, the antibody-targeted tumor cells delivered up to six times more drug into cells than did non-targeted, drug-laden liposomes. The research hypothesized that antibody binding to its target triggers endocytosis, a process that cells use to engulf large biomolecules for internalization. This work is reported in the journal Cancer Research. This work, which was supported by the National Cancer Institute, is detailed in a paper titled "Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models." Park is associate clinical professor in the Division of Hematology-Oncology at the University of California, San Francisco.

"Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models" Dmitri B. Kirpotin, Daryl C. Drummond, Yi Shao, M. Refaat Shalaby, Keelung Hong, Ulrik B. Nielsen, James D. Marks, Christopher C. Benz and John W. Park Cancer Research 2006 66: 6732-6740 Abstract | Full Text | Full Text (PDF)