title: 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.
authors.affiliation: Case Western Reserve University, Biomedical Engineering, Cleveland, Ohio 44106, USA.
authors.forename: Madhumitha
authors.initials: M
authors.lastname: Ravikumar
authors.forename: Christa L
authors.initials: CL
authors.lastname: Modery
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Wong
authors.forename: Anirban Sen
authors.initials: AS
authors.lastname: Gupta
mesh_terms: D000328:Adult; D001360:Avidin / Q000737:chemistry; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D012016:Reference Values; D013499:Surface Properties; D057772:Vascular System Injuries / Q000378:metabolism* / Q000473:pathology
chemical_list: D008081:Liposomes; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D001360:Avidin