Study on the capture and thrombolytic efficacy of magnetic particle clusters under a deeply focused rotating magnetic field

Magnetic particle-mediated targeted delivery of tissue plasminogen activator (tPA), assisted by a rotating magnetic field (RMF), represents a highly promising approach for the treatment of venous thrombosis. However, existing magnetic strategies face bottlenecks in deep tissues and complex hemodynamics due to poor focusing and weak flow resistance. Consequently, flow washout induces particle escape, while magnetic attenuation severely limits the clusters ' operating range and fluid perturbation. Achieving deep focusing and flow-resistant retention of magnetic particle clusters (MPCs) under deep-tissue, high-flow conditions remains a critical challenge for the clinical translation of this technology. To this end, a novel deeply focused rotating magnetic field (DF-RMF) system driven by dual synchronized rotating permanent magnets is developed. It establishes an axial magnetic focusing zone with dual-peak confinement and continuous centripetal properties to effectively counteract fluid drag. Simulations and in vitro flow experiments demonstrate that the DF-RMF stably confines magnetic particle clusters as compact, continuously rotating clusters at the lumen center. This effectively expands their geometric working boundaries and significantly enhances synergistic thrombolytic efficacy. Even at distances up to 5 cm or under the normal physiological flow velocity of lower extremity veins (~14 cm/s), the system maintains a substantial particle retention rate. Rotating synchronously under the DF-RMF, the clusters generate mechanical shear while inducing intense microfluidic circulation and pressure fluctuations. This physically disrupts the thrombus and accelerates interfacial tPA transport to boost fibrinolysis, achieving complete in vitro recanalization with a removal rate ~5 times that of tPA alone. This study provides a novel physical modulation strategy with translational potential for deep, precision targeted delivery and synergistic mechanical-biochemical thrombolysis in complex blood flow environments.