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Clot Buster Shoots Straight to Problem

Clusters of nanoparticles break apart and release an anti-clotting drug when they encounter vascular narrowing. (Graphic courtesy of Wyss Institute)
Scientists have developed a safer, more effective way to deliver a life-saving anti-clotting drug to people with obstructed blood vessels.

Researchers found that, when microscopically small nanoparticles were coated with the drug and injected into the bloodstream, the particles targeted clogged vessels and the drug coating dissolved the clots before they could cause damage or death.

Blood clots are responsible for a variety of life-threatening conditions, including heart attack, stroke and a lung blockage known as a pulmonary embolism. There are several effective anti-clotting agents that doctors can use to clear these clogged blood vessels, including one called tissue plasminogen activator, or tPA.

But like other anti-clotting agents, tPA carries a significant risk of causing potentially fatal internal bleeding. So doctors must weigh tPA's benefits against its risk to seriously ill patients.

Now, an experimental drug involving nanotherapeutic technology could eliminate tPA's risk.

Don Ingber is director of the Wyss Institute for Biologically Inspired Engineering at Harvard University. Ingber says that tPA-coated clusters of nanoparticles, each no bigger than the platelets that help form blood clots, can seek out the clots, quickly bind to them and break them down.

"It travels around your blood vessels in the bloodstream as this larger particle that's the size of a platelet," Ingber says. "And then when it sees a narrowing of vessels, it breaks up into the grains which then stick to the clot and digest it."

The nanoparticles are made from a biodegradable polymer or plastic, similar to dissolving surgical stitches, and are held together by a static charge. Each particle is coated with miniscule amounts of tPA, the kind of trace amounts used by practitioners in the alternative medicine field, homeopathy.

"We're able to use one-fiftieth to one one-hundredth of the dose, which basically is almost homeopathic if you inject it, it doesn't do anything," Ingber says. "But by putting it on these little small particles that only release it when they see the occlusion [blockage], all of them get concentrated at that site. So we are able to dissolve the blood clot efficiently with a much, much lower dose and those lower side effects."

Researchers injected experimental mice with blood clots that went to their lungs. The animals died in less than an hour. But 80 percent of mice treated with the nanotherapeutic drug survived.