Novel Strategy Delivers tPA-Coated Nanoparticles Directly to Occluded Blood Vessels (With Video)

  Image courtesy of the Wyss Institute.

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have developed a novel biomimetic strategy that delivers nanotherapeutics directly to obstructed blood vessels, dissolving blood clots before they cause serious damage or death (see video below).

This approach could lead to safer and more effective therapeutic strategies against life-threatening clots in patients with pulmonary embolism, stroke, and myocardial infarction. In addition, this new approach enables thrombus dissolution while using only a fraction of the drug dose normally required, thereby minimizing bleeding complications that currently limit widespread use of clot-busting drugs. The research findings were ported by Korin et al online ahead of print July 5 by the journal Science.

The vascular nanotherapeutic is about the size of a platelet, but it is an aggregate of biodegradable nanoparticles that have been coated with tissue plasminogen activator (tPA). Much like when a wet ball of sand breaks up into individual grains when it is sheared between two hands, the aggregates selectively dissociate and release tPA-coated nanoparticles that bind to clots and degrade them when they sense high shear stress in regions of vascular narrowing, such as caused by blood clot formation.

By targeting and concentrating the drug at the precise site of the blood vessel obstruction, the Wyss team has been able to achieve improved survival in mice with occluded lung vessels with less than 1/50th of the normal therapeutic dose, which should translate into fewer adverse effects and greater safety. This raises the possibility that, in the future, an emergency technician might be able to immediately administer this nanotherapeutic to anyone suspected of having a life-threatening blood clot in a vital organ before the patient even reaches the hospital.

A blood clot within a mouse artery disappears following the injection of a clot-busting, shear-activated nanotherapeutic. The bright areas are fluorescent-labeled platelets. Video courtesy of the Wyss Institute for Biologically Inspired Engineering at Harvard University.