Ultrasound Controlled Anti-Inflammatory Polarization of Platelet Decorated Microglia for Targeted Ischemic Stroke Therapy
Ultrasound Controlled Anti-Inflammatory Polarization of Platelet Decorated Microglia for Targeted Ischemic Stroke Therapy
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DOI：
10.1002/anie.202010391
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发表时间：
2021-01-22
影响因子：
16.6
通讯作者：
Li, Jinghong
中科院分区：
文献类型：
--
作者：
Li, Yujie;Teng, Xucong;Li, Jinghong
脑卒中是一种致死性脑疾病，后遗症严重，死亡率高。小胶质细胞是大脑中的主要免疫细胞，具有治疗中风的潜力，因为其特异性抗炎表型可以减轻炎症并促进神经元再生。然而，中风部位的小胶质细胞的按需抗炎极化对于治疗应用是不可控制的。在这里，我们开发了一个血小板杂交小胶质细胞平台，它可以通过超声照射特异性地结合到抗炎表型，用于脑卒中后的靶向大脑修复。该工程化小胶质细胞具有与损伤的脑血管的强粘附性和血小板膜融合，并通过超声响应性IL-4脂质体修饰实现按需抗炎极化。静脉内注射的小胶质细胞平台显示出在中风部位用声波照射的抗炎极化，并加速内源性小胶质细胞的M2型极化，用于长期中风恢复。通过减少细胞凋亡，促进神经发生和功能恢复实现了满意的治疗，表明小胶质细胞平台对卒中治疗的意义。
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.