Peptide-decorated liposomes promote arrest and aggregation of activated platelets under flow on vascular injury relevant protein surfaces in vitro

Biomacromolecules. 2012 May 14;13(5):1495-502. doi: 10.1021/bm300192t. Epub 2012 Apr 16.

Abstract

Platelet-mimetic synthetic hemostats are highly attractive in transfusion medicine. To this end, past research reports have described particles that either amplify platelet aggregation or mimic platelet adhesion. However, a construct design that effectively combines both functionalities has not been reported. Here we describe the design of a liposomal construct simultaneously surface-decorated with three peptides (a vWF-binding peptide (VBP), a collagen-binding peptide (CBP), and an active platelet clustering cyclic-RGD (cRGD) peptide), that can integrate platelet-mimetic dual hemostatic activities of adhesion and aggregation. We first demonstrate that surface-immobilized cRGD-liposomes are capable of aggregating activated platelets onto themselves. Subsequently, we demonstrate that hetero-multivalent liposomes bearing VBP, CBP, and cRGD, when introduced in flow with ≈ 20,000 activated platelets per microliter, are capable of adhering to vWF/collagen surfaces and promoting the recruitment/aggregation of platelets onto themselves. We envision that optimizing this construct can lead to a highly refined synthetic hemostat design for potential application in transfusion medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Avidin / chemistry
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Humans
  • Liposomes / chemistry
  • Liposomes / pharmacology*
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Platelet Adhesiveness / drug effects
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / pharmacology*
  • Reference Values
  • Surface Properties
  • Vascular System Injuries / metabolism*
  • Vascular System Injuries / pathology

Substances

  • Liposomes
  • Peptides
  • Platelet Aggregation Inhibitors
  • Avidin