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One nanoparticle plus one antibody equals targeted drug delivery to tumors

Posted July 16, 2013

Herceptin and camptothecin are both powerful anticancer agents with key characteristics that limit their effectiveness in treating cancer. Patients treated with Herceptin, a monoclonal antibody that targets a growth promoting factor common to breast cancers (Her2), often relapse as their tumors become resistant to the drug. overcoming camptothecin”s toxicity and low solubility represent major therapeutic challenges. Now, researchers at the California Institute of Technology have used nanotechnology to combine the two into what so far appears to be a highly effective drug for treating aggressive breast cancer.

Mark E. Davis and his graduate student Han Han report their developmental work in the journal Molecular Pharmaceutics. Dr. Davis is also a project leader at Caltech’s Center of Cancer Nanotechnology Excellence.

Drugs based on monoclonal antibodies and nanoparticles are not new, but what Dr. Davis and Ms. Han have done for the first time is use a single antibody molecule, bound to a nanoparticle, as both a targeting agent for that drug-loaded nanoparticle and a therapeutic agent. They created this construct by first linking insoluble camptothecin to a natural biopolymer known as mucin and the widely used biocompatible polymer, polyethylene glycol (PEG). The camptothecin-mucin-PEG combination self-assembles into a tightly packed nanoparticle that readily dissolves in water and biological fluids such as blood. They then chemically linked one molecule of Herceptin per nanoparticle to create their final therapeutic agent.

In a previous study the group showed that a line of aggressive breast tumor cells that overexpress the Her2 protein readily took up the Herceptin-linked nanoparticle. Based on these results, the Caltech researchers conducted tests in mice with tumors grown from this same cell line, which cancer researchers consider one of the most resistant cell lines to anticancer drugs, including camptothecin. First, they determined the maximum tolerated dose of the camptothecin nanoparticle drug without Herceptin, that is, the highest dose that would not cause the mice to lose more than 15 percent of their body weight. They then treated tumor-bearing animals with a dose of the Herceptin-bound nanoparticle that was approximately 10 percent of this maximum tolerated dose.

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