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Biological Chemistry

Dendrimer-DOX slays cancer cells in mice

November 6, 2006 | APPEARED IN VOLUME 84, ISSUE 45

By attaching the anticancer drug doxorubicin (DOX) to a bow-tie-shaped polyester dendrimer, scientists have created a chemotherapeutic delivery system that can cure mice of certain colon carcinomas (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.0607705103). The dendrimer-DOX hybrid, developed by Jean M. J. Frèchet of the University of California, Berkeley, and Francis C. Szoka of the University of California, San Francisco, exploits a dendrimer's pharmacokinetics-regulating ability. As bulky, high-molecular-weight polymers, dendrimers tend to penetrate and accumulate in a tumor's leaky vasculature. Their size and branched structure also make them less susceptible to the quick circulatory clearance that often eliminates drugs such as DOX from the body before they even reach tumors. Frèchet and Szoka's team grafted DOX onto one half of the asymmetric biodegradable bow-tie dendrimer, creating a system that uses a minimal amount of the toxic drug to maximum effect. Mice with C-26 colon carcinomas—tumors known to be insensitive to DOX—exhibited complete tumor regression after a single injection of the dendrimer-DOX hybrid.

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