Novel Platelet-Like PLGA-PSP Nanoparticles Based on Platelet-Specific Peptides Alleviated Traumatic Hemorrhage.

Background: Platelets play a crucial role in regulating coagulation. However, balancing the supply and clinical demands of platelet concentrates is a tough challenge. It is urgent to explore a novel platelet substitute with biosafety and efficacy in traumatic hemorrhage. Methods: The platelet-like PLGA-PSP nanoparticles were synthesized by covalently coupling the linear platelet-specific peptides including CBP, VBP and FMP to the active carboxyl functional group of PLGA-PEG nanoparticles. The biosafety of the platelet-like PLGA-PSP nanoparticles was assessed. Subsequently, in vitro experiments were conducted to verify the effects of PLGA-PSP nanoparticles on platelet adhesion, aggregation and activation. Furthermore, the hemostatic efficacy of PLGA-PSP nanoparticles was confirmed in the tail vein, liver and femoral artery hemorrhage of normal and thrombocytopenic mice. Results: We successfully designed and synthesized the non-toxic PLGA-PSP nanoparticles with specific hemostatic ability that significantly induced platelet adhesion and aggregation without triggering unexpected platelet activation. Moreover, the application of PLGA-PSP nanoparticles was demonstrated to effectively reduce the bleeding time and blood loss in the tail vein, liver and femoral artery of both normal and thrombocytopenic mice. Conclusion: The novel platelet-like PLGA-PSP nanoparticles present a promising therapeutic option for the rapid hemostasis of traumatic hemorrhage based on the biosafety and efficacy.