Department of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Shanghai, 200233, P. R. China.
Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu, 215123, P. R. China.
Adv Mater. 2021 Dec;33(51):e2105351. doi: 10.1002/adma.202105351. Epub 2021 Oct 13.
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.
利用组织型纤溶酶原激活物（tPA）进行快速有效的溶栓治疗受到溶栓药物输送效率低下的限制，这是由于血流中断和再通延迟所致。现有的用于靶向血栓治疗的磁性微/纳米载药机器人受到纳米药物临床验证的复杂性和磁驱动系统空间有限的限制。在此，提出了一种基于质量输运理论的溶栓通用药物输送策略，并开发了一种具有激光定位和超声成像导航的开放式 C 形磁驱动系统，用于体内评估。通过磁纳米颗粒群（MNS）的运动，tPA 可以穿过血流中断到达血栓，从而提高溶栓效果。值得注意的是，该策略能够快速建立生命通道，实现时间关键的再通，而这通常是使用天然 tPA 无法实现的。体外和体内溶栓实验表明，在旋转磁场下应用 MNS 后，血栓溶解效果显著提高。本研究为体内验证提供了一种预期的 C 形磁驱动系统，也为具有最小全身 tPA 暴露的靶向溶栓治疗提供了一种临床可行的药物输送策略。
