Guiding Drug Through Interrupted Bloodstream for Potentiated Thrombolysis by C‐Shaped Magnetic Actuation System In Vivo

• Published in: Advanced materials (Weinheim) 2021-12, Vol.33 (51), p.e2105351-n/a
• Main Authors: Wang, Longchen, Wang, Jienan, Hao, Junnian, Dong, Ziliang, Wu, Jianrong, Shen, Guofeng, Ying, Tao, Feng, Liangzhu, Cai, Xiaojun, Liu, Zhuang, Zheng, Yuanyi
• Format: Article
• Language: English
• Subjects: Actuation; Animals; C‐shaped magnetic actuation systems; drug delivery; Drug Delivery Systems - instrumentation; Fibrinolytic Agents - chemistry; Fibrinolytic Agents - pharmacology; Fibrinolytic Agents - therapeutic use; Humans; In vivo methods and tests; Locomotion; Magnetic Fields; magnetic micro/nanorobots; magnetic nanoparticle swarms; Magnetite Nanoparticles - chemistry; Materials science; Mice; Nanoparticles; thrombolysis; Thrombolytic Therapy - methods; Thrombosis - drug therapy; Tissue Plasminogen Activator
• ISSN: 0935-9648; 1521-4095; 1521-4095
• DOI: 10.1002/adma.202105351

Fast and effective thrombolysis using tissue plasminogen activator (tPA) is limited by the poor delivery efficiency of thrombolytic drugs, which is induced by an interrupted bloodstream and delayed recanalization. Existing magnetic micro/nanodrug‐loaded robots used for targeted thrombotic therapy are limited by the complexity of the clinical verification of nanodrugs and the limited space of magnetic actuation systems. Herein, a general drug delivery strategy based on mass transportation theory for thrombolysis is presented, and an open space C‐shaped magnetic actuation system with laser location and ultrasound imaging navigation for in vivo evaluation is developed. tPA can be guided through an interrupted bloodstream to the thrombi by the locomotion of magnetic nanoparticle swarms (MNSs), thereby improving the thrombolysis efficacy. Notably, this strategy is able to quickly establish a life channel to achieve time‐critical recanalization, which is typically inaccessible using native tPA. Both in vitro and in vivo thrombolysis experiments demonstrate that the thrombus lysis efficacy significantly increases after the application of the MNS under a rotating magnetic field. This study provides an anticipated C‐shaped magnetic actuation system for in vivo validation and also presents a clinically feasible drug delivery strategy for targeted thrombolytic therapy with minimal systemic tPA exposure. Manipulation of magnetic nanoparticle swarms (MNSs) for thrombolysis is validated in in vivo experiments with an autonomously developed C‐shaped magnetic actuation system. Accompanied by the locomotion of MNSs, a tissue plasminogen activator (tPA) can be transported along with the swarms through the interrupted bloodstream to the clots, thus improving the thrombolysis efficacy and quickly opening a channel for achieving time‐critical recanalization.