新型血小板膜仿生纳米递药系统的构建及其在逆转动脉粥样硬化易损斑块中的作用研究

动脉粥样硬化性“易损斑块”发生破裂是心脑血管急症发生的重要病理基础。我们前期研究表明，血小板被激活后所产生的微粒（PMPs）可促进单核细胞炎症因子的释放、内皮细胞迁移和管腔形成、以及加速动脉粥样硬化病变的发生和发展；我们采用β-环糊精为纳米材料，连接氧化应激响应性单元（对羟甲基苯硼酸频哪醇酯），包载抗氧化应激药物Tempol，可有效抑制动脉粥样硬化和减轻局部炎症反应。因此，探索能够靶向于易损斑块并使其逆转的有效方法具有重要意义。在此基础上，本项目拟构建新型血小板膜仿生纳米系统，主要包括：①血小板膜可使纳米药物主动靶向于易损斑块，并可竞争性的减少血小板和PMPs的聚积，从而减少血栓形成和局部炎症加剧的风险；②Tempol可有效抑制动脉粥样硬化病变的形成；③环肽配体（cRGDfK）可与整合素αvβ3结合，靶向于斑块内的新生血管，减少斑块内出血的发生，从而为心脑血管疾病的防治提供新的有效方法。

The rupture of atherosclerotic vulnerable plaque (VP) is an important pathological basis for the occurrence of cardiovascular and cerebrovascular emergencies. Our previous studies have shown that the microparticles (PMPs) released by activated platelets can promote monocytes to release the inflammatory factors, endothelial cell migration and angiogenesis, accelerate the development of atherosclerotic lesions as well; We also constructed a nanosystem including β-cyclodextrin connected to 4-(Hydroxymethyl) phenylboronic acid pinacolester (PBAP), containing the anti-oxidative stress drug Tempol,which could effectively inhibit atherosclerotic lesion and inflammation. Therefore, it is of great significance to explore effective treatments that can quickly target and reverse VP. This project intends to construct a novel platelet-membrane-biomimetic nanosystem and study its role in reversing vulnerable atherosclerotic plaques, its effects mainly include:① Platelet membrane can actively target the vulnerable plaques quickly, and competitively reduce the accumulation of platelets and PMPs, thereby reducing the risk of thrombosis and aggravation of local inflammation;②Tempol can effectively inhibit the formation of atherosclerosis; ③Cyclopeptide ligand (cRGDfK) can bind to integrin αvβ3, targeting neovascularization in plaque, and reduce the occurrence of intra-plaque hemorrhage (IPH).Our findings would provide a new and effective method for the prevention and treatment of cardiovascular and cerebrovascular diseases.