Nanotech Revives a Cancer Drug

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Folkman, who died in January, encouraged another researcher in his lab, Ofra Benny, to develop a version of TNP-470 that could be taken orally. Benny encased the drug in a micelle, a spherical polymer coating that resembles the fluff on a dandelion. The micelle, which is about 10 nanometers in diameter, is made up of two polymers that are both already FDA approved. Benny tested the new formulation, called Lodamin, in mouse models of melanoma and lung cancer. Her results, recently published in Nature Biotechnology, show that Lodamin is as effective as TNP-470--without having its toxicity. Hidden in the micelle, the drug is absorbed by the intestine into the bloodstream. First, it reaches the liver--a common site of secondary tumor growth--and then selectively accumulates in tumors throughout the body, inhibiting their growth.

The National Cancer Institute's Grodzinski says that the potential for Lodamin to be taken orally is significant. "If it's successful, that simplifies the treatment: you don't have to come to the clinic to take it," he says. The use of micelles for this purpose is novel, says Ingber, and could be applied to a range of other small-molecule drugs. Simple treatments with fewer side effects that keep small tumors from becoming dangerous are "the future for angiogenesis inhibitors," he says, and will help cancer therapies keep pace with cancer diagnostics. "Early diagnosis is getting better, but we have nothing to offer these people."

The group at Children's Hospital is also developing Lodamin for other blood-vessel diseases, including some forms of blindness and arthritic pain caused by the invasion of capillaries into cartilage. Biotechnology company SynDevRx, based in Cambridge, MA, has optioned Lodamin for clinical development and is trying to bring it to clinical trials, says Ingber.