Ultrasound controlled anti‐inflammatory polarization of platelet decorated microglia for targeted ischemic stroke therapy

Stroke is a neurological disease with poor prognosis. Strong inflammatory and immune response exist after stroke, resulting in severe sequelae with high mortality. Microglia, the main immune cell in cerebrum, possess therapeutic potential for stroke as its specific anti-inflammatory phenotype can reduce inflammation and promote neuron regeneration. However, the on-demand anti-inflammatory polarization of microglia at stroke site is uncontrollable for therapeutic application. Here, we develop a platelet hybrid microglia platform which can specifically polarize to anti-inflammatory phenotype by ultrasound irradiation for targeted cerebrum repair after stroke. The engineered microglia have strong adherence to the injured cerebral vessels with platelet membrane fusion and can realize on-demand anti-inflammatory polarization with the ultrasound responsive IL-4 liposome decoration. Intravenously injected microglia platform showed anticipated anti-inflammatory polarization at stroke site with insonation control and accelerated the M2-type polarization of endogenous microglia for long-tern stroke recovery. Satisfied prognoses were achieved with reduced apoptosis, promoted neurogenesis and functional recovery, indicating the implications of microglia platform for stroke therapy.