Platelet membrane-functionalized nanoparticles with improved targeting ability and lower hemorrhagic risk for thrombolysis therapy.

Abstract Intravenous injection of thrombolytic drugs is the most effective strategy for the treatment of thrombotic diseases. However, the clinical application of most thrombolytic drugs is limited by hemorrhagic risks and narrow therapeutic index. The targeted drug delivery systems may help to address these problems. Inspired by the crucial role of platelets in the process of thrombus, Platelet membrane-coated PLGA cores loading lumbrokinase (PNPs/LBK) were designed for effective thrombolysis with reduced hemorrhagic risk. Using a mouse carotid thrombosis model, the affinity of platelet membrane-coated nanoparticles to the thrombus was confirmed. Also, the PNPs/LBK exhibited excellent thrombolytic efficacy at a low dose, compared with free LBK. More importantly, PNPs/LBK showed less adverse effect on the function of the coagulation system, and thus reduced hemorrhagic risk. These results indicated that a promising thrombus-targeted drug delivery system was achieved by coating PLGA nanoparticles with platelet membrane. Such rationally designed drug delivery system will provide a broad platform for thrombus treatment.