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Dynamic duo: Nanoparticle/prodrug combination finds and fights tumors, files reports

Hazard_Journal of Small_COVER_v04Routine chemotherapy is a somewhat sloppy way of combating cancer, because the drugs employed work by killing rapidly dividing cells, not just cancerous ones. Hair cells, skin cells, the immune system, cells lining the intestine, and even a small but critical set of cells in the brain necessary for forging new memories - all these can be adversely affected.

But a Stanford team under the direction of radiologist/physician Heike Daldrup-Link, MD, and chemist Jianghong Rao, PhD, has produced a seek-and-destroy cancer therapy that could sharpen the attack while simultaneously making it easier to noninvasively visualize the therapy's progress. In a study just published in the nanotechnology journal Small, the team describes the linking of an easily imaged, FDA-approved iron-rich nanoparticle, ferumoxytol, to a prodrug (a compound that, while lacking activity on its own, can get converted in the body into a potent drug).

The key to the success of this so-called theranostic is the pummeling it gets from matrix metalloproteinases, a family of enzymes that make their living by breaking down the molecular latticework that positions cells within  tissues. Most tumors are particularly rife with one of this family's members, MMP-14, whose activities help tumors invade other, healthy tissues. Conveniently, MMP-14 is precisely the enzyme best equipped to carve up the prodrug,  releasing its active component. MMP-14 is found not only on tumor cells but, importantly, on the tiny blood vessels that pervade and feed them. When the theranostic particles, circulating in the bloodstream upon intravenous administration, reach those blood vessels, the drug is released, causing the vessels to cave in and starving the tumor mass that so depends on them.

The nanoparticles tend to stick around inside the collapsed microvasculature, allowing radiologists to see just where the drug has done its job (and, by extension, where cancerous lesions, including previously unknown ones, are in the body). Meanwhile healthy tissues are spared, tests in mice suggest.

Previously: Iron-supplement-slurping stem cells can be transplanted, then tracked to make sure they're making new knees and Nano-hitchhikers ride stem cells into heart, let researchers watch in real time and weeks later
Image provided by Kim Gray Hazard

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