Ultrasound Controlled Anti‐Inflammatory Polarization of Platelet Decorated Microglia for Targeted Ischemic Stroke Therapy

Stroke is a lethal cerebral disease with severe sequelae and high mortality. Microglia, the main immune cell in the cerebrum, possess therapeutic potential for strokes as its specific anti‐inflammatory phenotype can reduce inflammation and promote neuron regeneration. However, the on‐demand anti‐inflammatory polarization of microglia at the stroke site is uncontrollable for therapeutic application. Here, we develop a platelet hybrid microglia platform which can specifically polarize to the 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 realize on‐demand anti‐inflammatory polarization with ultrasound‐responsive IL‐4 liposome decoration. The intravenously injected microglia platform showed anti‐inflammatory polarization at the stroke site with insonation, and accelerated the M2‐type polarization of endogenous microglia for long‐term stroke recovery. Satisfied prognoses were achieved with reduced apoptosis, promoted neurogenesis, and functional recovery, indicating the implications of the microglia platform for stroke therapy. To realize on‐demand microglia polarization for controllable ischemic stroke therapy, a sono‐sensitive hybrid microglia machine was prepared. Platelet membrane fused microglia have strong accumulation in cerebral vascular injury and can specifically polarize to anti‐inflammatory phenotypes, upon external control by ultrasound irradiation, for angiogenesis and nerve regeneration, leading to survival and behavioral improvement of the stroke mice.