在血栓栓塞性疾病治疗中，纤维蛋白聚合网络的致密结构，是导致药物溶栓效率低的重要原因。而由非共价键形成的“knob-hole杵臼结构”，是引起纤维蛋白聚合及维持其结构稳定的关键因素。基于此，本项目提出磁力解锁血纤蛋白“knob-hole杵臼结构”的创新策略，拟借助新型空心梭形磁性纳米颗粒响应外加磁场旋转产生的机械力，特异性解锁血纤蛋白的“knob-hole杵臼结构”，继而破坏纤维蛋白致密稳定的机械稳态，使其构象变得松散，以显著增加纤溶酶结合密度；同时，装载其中的溶栓药物，可响应磁场在血栓部位定向释放，从而实现基于磁力解锁的高效药物溶栓，并对机械力破坏纤维蛋白结构提升药物溶栓效率的协同机制进行探索。这种基于外加磁场调控多功能磁性纳米粒子的非侵入式治疗手段，为药物溶栓提供了一种高效、安全、便捷的新型治疗方式，具有潜在的临床应用价值，也为物理机械力在疾病治疗中的应用提供新的思路。

For thromboembolic diseases, the dense structure of the polymerized fibrin is an important obstacle for drug thrombolysis. And the "knob-hole structure" of fibrin formed by non-covalent bonds is the key factor for fibrin formation and to maintain its structural stability.The efficiency of drug thrombolysis is an urgent problem to be solved. The dense structure of the polymerized fibrin network prevents plasmin from binding more enzymatic hydrolysis sites, which is the main reason for low degradation efficiency of thrombolytic drugs. To this end, we propose an innovative strategy of magnetically unlock the “knob into hole” structure of fibrin. We prepare a new type of hollow spindle-shaped magnetic particles. With the help of the magnetic force generated by the rotation of the spindle-shaped magnetic nanoparticles in response to an applied rotation magnetic field, the "knob into hole structure is unlocked and thereby destroy the dense and stable mechanical homeostasis of fibrin. Fibrin with a loose conformation provide a broader binding front and was cleaved at a faster rate. Meanwhile, the thrombolytic drugs loaded in the nanoparticles can be controlled release at the thrombus site, thereby achieving high-efficient thrombolysis based on magnetic mechanical force. The synergistic mechanism of fibrin conformation and improving thrombolytic efficiency was also explored. This kind of non-invasive thrombolysis therapy based on external magnetic mechanical force provides a new, efficient, safe and convenient strategy for drug thrombolysis, which has clinical application potential; at the same time, this strategy also provides creative ideas for the application of physical mechanical force in disease treatment.