靶向载TSP-1/PLGA纳米微囊联合UTMD可视化抑制血管新生以促进易损斑块稳定的实验研究

脑卒中致死致残率极高。目前研究认为，抑制斑块内血管新生会减少斑块易损性，从而降低脑卒中风险。我们前期动脉硬化体内体外研究均显示：TSP-1与CD47受体结合可以显著抑制血管新生，TSP-1是斑块内血管新生负性调控的关键分子。为了实现TSP-1的靶向递送，本研究拟利用纳米材料PLGA作为外壳，有效包裹TSP-1，并充入SF6气体为核心，表面枝接可识别斑块内血管内皮细胞的靶向抗体cRGD肽，构建新型的靶向诊疗体R-MBs-TSP-1微囊。借助细胞实验及动脉硬化动物模型（1）探索R-MBs-TSP-1联合UTMD是否可促进微囊更多进入斑块内，靶向释放TSP-1抑制血管新生，增加斑块稳定性；（2）在超声造影模式下R-MBs-TSP-1是否可以实时成像，治疗的同时可视化评估疗效。本研究将对易损斑块内调控血管新生建立一种分子靶向辅助诊疗一体化新模式，为脑卒中的治疗提供新策略。

Mortality and disability rates associated with stroke are alarming. Current studies suggest that the inhibition of angiogenesis in plaques can reduce their vulnerability, thereby reducing the risk of stroke. Our previous in vivo and in vitro studies on atherosclerosis have shown that TSP-1 binding to the CD47 receptor can significantly inhibit angiogenesis, and that TSP-1 is a key molecule in the negative regulation of angiogenesis in plaques. This study intends to use PLGA as a shell for the targeted delivery of TSP-1, effectively encapsulating TSP-1, and filled with SF6 gas as the core. The surface of PLGA is branched with the cRGD peptide, which can recognize plaque neovascular endothelial cells and construct a new type of targeted diagnosis and treatment employing R-MBs-TSP-1 nanocapsules. Using cell experiments and an arteriosclerosis animal model, we aim to investigate (1) whether R-MBs-TSP-1 combined with UTMD can promote the entry of more nanocapsules into the plaque, target the release of TSP-1, inhibit angiogenesis, and increase plaque stability; and (2) whether R-MBs-TSP-1 can be imaged in real-time in contrast-enhanced ultrasound mode, and concurrently assess the curative effect visually. This study will establish a new model of molecular targeting-assisted diagnosis and treatment for the regulation of angiogenesis in vulnerable plaques and will provide a new strategy for the treatment of stroke.