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

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.