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Nanoparticles vs. Clots: New 'Shotgun' Approach Dissolves Blood Clots In Mice

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The shear-activated nanotherapeutic breaks apart and releases its drug when it encounters regions of vascular narrowing. | Wyss Institute for Biologically Inspired Engineeri

By Krystnell A. Storr

Think of it as Liquid-Plumr for the circulatory system. Researchers have designed a clump of tiny particles that rides the current of the bloodstream, seeks out life-threatening blood clots, and obliterates them. The approach works in mice and could soon move on to human trials.

Blood clots are bad news for the brain, heart, and other organs. These masses of blood cells can grow big enough to choke off veins and arteries, preventing oxygen from flowing to critical organs. One of the chief obstacles to dealing with blood clots is finding where they have lodged in the body. Even if doctors locate clots, they're hard to get rid of. Doctors often prescribe blood thinners that slow down the time it takes a clot to form, but such medication can also cause excessive bleeding. Another method is stenting, a procedure in which a flexible wire or tube is used to reopen a vessel. Patients recover quickly but often spend at least 1 night in the hospital.

Looking for a better approach, biomedical engineer Donald Ingber of Harvard University and colleagues turned to nanoparticles. Modeled after platelets—cells that circulate in the blood and help stop bleeding by forming clots—the nanoparticles are less than 100 nm wide and made of synthetic polymers stuck together like a ball of wet sand. Like platelets, clumps of the particles flow freely in the blood and gravitate toward blocked vessels by sensing a change in blood flow. Once there, they break apart into individual particles that stick to the clot, releasing a drug called tissue plasminogen activator (tPA) that dissolves it.

A blood clot within a mouse artery disappears following the injection of clot-busting nanoparticles. The bright areas are fluorescently labeled platelets.

The researchers tested the approach on mice suffering from blood clots. After they injected the particles into the animals, the particles coated in tPA were able to reopen the blocked vessels quickly, despite harboring low dosages of medicine, the team reports online today in Science. None of the mice had uncontrolled bleeding, and because the particles are biodegradable, they are eventually broken down by the body.

"Making these particles so that they break apart at the right amount of force was a challenge," says Ingber. "The most exciting thing that we are able to do is deliver a clot-busting drug directly to a site where a clot is, without knowing where it is." He says that the particles could be used to deliver essentially any drug—an anti-inflammatory to a specific spot where inflammation was occurring, for example.

"The beauty of these nanoparticles is that they will not deliver this drug to any other place but the area of stress," says Heyu Ni, platelet biologist at St. Michael's Hospital in Toronto, Canada, specifically referring to blood clot sites. Another advantage of the approach, he says, is that it gets around the issue of estimating the amount of anticlotting medication to give a patient. High dosages are effective but could cause excessive bleeding, whereas small doses are much safer but may not get the job done. The nanoparticles skirt this problem by depositing a small amount of medication directly on the clot. He notes that the nanoparticles could be used as a diagnostic tool to seek out blockages that may need to be removed surgically, since places where the nanoparticles wind up are easier to spot with ultrasound. "This could change our concept of how to deliver drugs effectively. I would think of this study as possibly revolutionary."

ScienceNOW, the daily online news service of the journal Science

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