Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels

Research output: Contribution to journalArticlepeer-review

Authors

  • Netanel Korin
  • Mathumai Kanapathipillai
  • Benjamin D Matthews
  • Marilena Crescente
  • Tadanori Mammoto
  • Kaustabh Ghosh
  • Samuel Jurek
  • Sidi A Bencherif
  • Deen Bhatta
  • Ahmet U Coskun
  • Charles L Feldman
  • Denisa D Wagner
  • Donald E Ingber

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)738-42
Number of pages5
JournalScience
Volume337
Issue number6095
Publication statusPublished - 10 Aug 2012

Keywords

  • Animals, Drug Delivery Systems, Blood Circulation, Pulmonary Embolism, Mesenteric Arteries, Tissue Plasminogen Activator, Hemodynamics, Lactic Acid, Fibrinolytic Agents, Mice, Nanoparticles, Biomimetic Materials, Thrombosis, Mesenteric Vascular Occlusion, Polyglycolic Acid, Stress, Mechanical, Mice, Inbred C57BL, Microfluidic Analytical Techniques, Male, Models, Anatomic, Hemorheology