Multi-functional platelet membrane-camouflaged nanoparticles reduce neuronal apoptosis and regulate microglial phenotype during ischemic injury

Abstract

Cerebral ischemic injury is an important factor affecting the prognosis of acute ischemic stroke (AIS). Neuronal apoptosis and the change in microglial phenotype have been implicated in the development of AIS. The changes in microglia from the M1 phenotype to the M2 phenotype could rescue neurons and reduce apoptosis. MiRNA-Let-7c reduced ischemic injury by regulating the survival of neurons and changing microglial phenotype. Here, we used the information regarding the changes in the brain microenvironment after ischemic injury and constructed pH-sensitive polymeric nanoparticles to deliver miRNA-Let-7c. The nanoparticles were coated with platelet membrane, which preserved the function of platelets while allowing nanoparticles to evade recognition by the immune system. The platelet membrane-camouflaged nanoparticles entered the neutrophils by endocytosis and used inflammatory chemotaxis of neutrophils to transport the vector across the blood–brain barrier (BBB). The platelet membrane-camouflaged nanoparticles efficiently localized to the area of the ischemic injury and delivered the miRNA-Let-7c for the targeted regulation of neurons and microglia. Based on these results, we conclude that this strategy is a favorable gene delivery system and could effectively treat ischemic injury.