Negatively charged nanoparticles of multiple materials inhibit shear-induced platelet accumulation

Michael T. Griffin, Katrina Ashworth, Nathaniel Hill, Jaydra von Behren, Jorge Di Paola, David N. Ku

Research output: Contribution to journalArticlepeer-review

Abstract

Platelet accumulation by VWF under high shear rates at the site of atherosclerotic plaque rupture leads to myocardial infarction and stroke. Current anti-platelet therapies remain ineffective for a large percentage of the population, while presenting significant risks for bleeding. We explore a novel way to inhibit arterial thrombus formation. Theoretically, a negative charge may influence the tertiary structure of VWF to favor the globular configuration by biophysical means without the use of platelet inactivating drugs. We tested this hypothesis experimentally for charged nanoparticles (CNPs) to inhibit thrombus formation in a microfluidic thrombosis assay (MTA). Several different CNPs demonstrated the ability to retard thrombotic occlusion in the MTA. A preliminary study in mice shows that thrombus stability is weaker with CNP administration and bleeding times are not markedly prolonged. The CNPs tested here show promise as a new class of antithrombotic therapies that act by biophysical means rather than biochemical pathways.

Original languageEnglish
Article number102405
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume35
DOIs
StatePublished - Jul 2021

Keywords

  • Charged nanoparticles
  • Platelets
  • Thrombosis
  • von Willebrand factor

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