Abstract
Ischemic stroke is a leading cause of death and disability worldwide, and the main goals of stroke treatment are to destroy the thrombus to recanalize blood vessels and protect tissue from ischemia/reperfusion injury. However, current recanalization therapies have serious limitations and there are few neuroprotection methods. Hence, an artificial nanoplatform loaded with anti-Repulsive Guidance Molecule a monoclonal antibody (anti-RGMa) and coated with microglia membrane (MiCM) is reported for stroke treatment, namely MiCM@PLGA/anti-RGMa/Fe3O4@PFH (MiCM-NPs). Tail vein injection of MiCM-NPs targeted the ischemia-damaged endothelial cells because of the MiCM, then superparamagnetic iron oxide (Fe3O4) and anti-RGMa are released after external low-intensity focused ultrasound (LIFU) exposure. The thrombus is destroyed by LIFU-induced "liquid-to-gas" phase transition and cavitation of perfluorohexane (PFH) as well as Fe3O4 movements induced by an external magnetic field. Anti-RGMa protected the ischemic region from ischemia/reperfusion injury. The nanoplatform enabled visualization of the thrombus by ultrasound/photoacoustic imaging when the clot is in an extracranial artery. Importantly, in vivo animal studies revealed good safety for MiCM-NPs treatment. In conclusion, this nanoplatform shows promise as an ischemic stroke treatment strategy combining targeted delivery, recanalization, and neuroprotection.