动脉血栓严重危害人类健康，研发高效、灵敏的药物递送系统，能够实现在体无创精准治疗以挽救缺血坏死组织，减少并发症，降低死亡率。因此，本项目结合前期研究基础，明胶（Gel）载溶栓药物（rtPA）、Fe3O4、荧光材料（BODIPY）及靶向血栓纤维蛋白多肽（CREKA），制备智能型纳米粒（Fe3O4/rtPA/BODIPY@Gel-CREKA），巨噬细胞吞噬智能型纳米粒构建基于声响应的仿生系统。利用巨噬细胞对血小板的趋化作用和磁导航增强血栓靶向性，低强度聚焦超声（LIFU）响应致智能型纳米粒从巨噬细胞中释放，以层层递进的方式到达血栓深部，再次LIFU响应实现智能释药，恢复rtPA的活性，增强溶栓效果。通过体内外实验验证其靶向性及其靶向深度，研究两相声响应的最佳参数以及增强溶栓效果机制，MRI/荧光成像监测溶栓效果，为溶栓治疗及活体动态监测提供一种安全、高效、无创的新方法，促进溶栓治疗技术的发展。

Arterial thrombosis is extremely harmful to human health, development of an efficient and sensitive drug delivery system can achieve the noninvasive and precise therapy to revive and save ischemic tissues and reduce complications and mortality. Based on our pilot research, this study constructs intelligent nanoparticles (Fe3O4/rtPA/BODIPY@Gel-CREKA)，which uses gelatin (Gel) carrying thrombolytic agents (rtPA), Fe3O4, fluorescent materials (BODIPY) and fibrin targeted polypeptide (CREKA) to build a biomimetic system based on acoustic response. The target ability is enhanced by using chemotactic effect of macrophage to platelets and the magnetic navigation. Then LIFU response releases the nanoparticle from the macrophage and it will reach into the deep thrombolus layer by layer. Again LIFU response releases the intelligent agent and revive the activity of rtPA, which enhances the thrombolytic effect. The targeting ability and thrombolytic depth are verified in vivo and vitro. The optimal parameters of two-phase acoustic response and the mechanism of enhancing thrombolytic effect are studied. The thrombolytic effect monitored by MRI/fluorescence imaging provides a safe, effective and noninvasive new method for thrombolytic therapy and dynamic monitoring in vivo.