A nanoparticle-based therapeutic strategy that mimics the behavior of blood platelets breaks up blood clots with minimal levels of clot-dissolving drugs.

Investigators at Harvard University’s Wyss Institute (Cambridge, MA, USA) devised a novel microscale aggregate comprised of nanoparticles coated with the clot-dissolving drug tissue plasminogen activator. The aggregates were designed to be injected into the blood stream where they would break up into discrete nanoparticles when exposed to areas of abnormally high fluid shear stress. Such areas could be caused by narrowing of blood vessels by atherosclerotic plaques.

Results published in the July 5, 2012, online edition of the journal Science revealed that when the coated aggregates were administered intravenously to mice, these shear-activated nanotherapeutics induced rapid clot dissolution in a mesenteric injury model, restored normal flow dynamics, and increased survival in an otherwise fatal mouse pulmonary embolism model.

By targeting and concentrating the drug at the precise site of the blood vessel obstruction, the investigators were able to achieve improved survival in mice with occluded lung vessels with less than 1/50th of the normal therapeutic dose.

Senior author Dr. Donald E. Ingber, professor of bioengineering at Harvard University, said, “The vascular nanotherapeutic we developed that selectively becomes activated in regions of high shear stress, much like living platelets do, is a wonderful example of how we at the Wyss Institute take inspiration from biology, and how biomimetic strategies can lead to new and unexpected solutions to age-old problems that existing technologies cannot address.”

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Harvard University’s Wyss Institute