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      Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels.

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          Abstract

          Obstruction of critical blood vessels due to thrombosis or embolism is a leading cause of death worldwide. Here, we describe a biomimetic strategy that uses high shear stress caused by vascular narrowing as a targeting mechanism--in the same way platelets do--to deliver drugs to obstructed blood vessels. Microscale aggregates of nanoparticles were fabricated to break up into nanoscale components when exposed to abnormally high fluid shear stress. When coated with tissue plasminogen activator and administered intravenously in mice, these shear-activated nanotherapeutics induce rapid clot dissolution in a mesenteric injury model, restore normal flow dynamics, and increase survival in an otherwise fatal mouse pulmonary embolism model. This biophysical strategy for drug targeting, which lowers required doses and minimizes side effects while maximizing drug efficacy, offers a potential new approach for treatment of life-threatening diseases that result from acute vascular occlusion.

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          Author and article information

          Journal
          Science
          Science (New York, N.Y.)
          1095-9203
          0036-8075
          Aug 10 2012
          : 337
          : 6095
          Affiliations
          [1 ] Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
          Article
          science.1217815
          10.1126/science.1217815
          22767894

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