NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou, 510275, China.
Small. 2024 Nov;20(47):e2403440. doi: 10.1002/smll.202403440. Epub 2024 Aug 16.
Current thrombolytic drugs exhibit suboptimal therapeutic outcomes and potential bleeding risks due to their limited circulation time, inadequate thrombus penetration, and off-target biodistribution. Herein, a photosensitizer-loaded, red cell membrane-encapsuled multiple magnetic nanoparticles aggregate is successfully developed for integrated mechanical/photothermal/photodynamic thrombolysis. Red cell membrane coating endows magnetic particles with prolonged blood circulation and superior biocompatibility. Under a preset rotating magnetic field (RMF), the aggregate with asymmetric magnetic distribution initiates rolling motion toward the blood clot interface, and because of magnetic dipole-dipole interactions, the aggregate tends to self-assemble into longer, flexible chain-like microrobotic swarm with powerful mechanical stir forces, thereby facilitating thrombus penetration and mechanical thrombolysis. Moreover, precise magnetic control enables targeted photosensitizer accumulation, allowing effective conversion of near-infrared (NIR) light into heat and reactive oxygen species (ROS) for thrombus phototherapy. In thrombolysis assays, the weight of thrombi is massively reduced by ≈90%. The work presents a safer and more promising combination of magnetic microrobotic technology and phototherapy for multi-modality thrombolysis.
目前的溶栓药物由于其循环时间有限、血栓穿透不足和非靶向生物分布，表现出不理想的治疗效果和潜在的出血风险。在此，我们成功开发了一种载有光敏剂的、红细胞膜包裹的多磁纳米颗粒聚集体，用于集成机械/光热/光动力溶栓。红细胞膜涂层赋予磁性颗粒更长的血液循环时间和更好的生物相容性。在预设的旋转磁场（RMF）下，具有不对称磁性分布的聚集体会朝着血栓界面开始滚动运动，并且由于磁偶极子相互作用，聚集体倾向于自组装成更长、更灵活的链状微机器人群，产生强大的机械搅拌力，从而促进血栓穿透和机械溶栓。此外，精确的磁场控制可以实现靶向光敏剂的积累，从而有效将近红外（NIR）光转化为热和活性氧（ROS），用于血栓光疗。在溶栓实验中，血栓的重量减少了约 90%。这项工作为多模式溶栓提供了一种更安全、更有前途的磁微机器人技术与光疗相结合的方法。
