Magnetic particle clusters with tunable thrombus penetration for enhanced thrombolysis.

Current magnetically controlled thrombolysis strategies often rely on complex micro-/nano-architectures or multimodal external field actuation, which increase technical cost and operational complexity. Developing a simple, efficient, and controllable strategy to overcome the structural barrier of thrombi therefore remains a major challenge. In this study, we propose a thrombolytic strategy based on pulsed magnetic field (PMF)-regulated magnetic particle clusters (MPCs). Using an in vitro thrombolysis platform, we systematically investigated the relationships between MPC-mediated penetration efficiency and key parameters, including PMF intensity and particle mass. We further characterized the time-dependent penetration behavior of MPCs in thrombi, optimized the pulse waveform, and evaluated the effect of penetration cycles on thrombolytic performance. The results show that PMF-driven MPCs can rapidly penetrate thrombi and form internal drug diffusion channels within 10 min. Compared with tPA treatment alone, thrombolysis was significantly enhanced after MPC-mediated penetration, and the enhancement increased with penetration cycle number. For 0.2 mg MPCs, the thrombolytic rate reached saturation after 15 penetration cycles and was more than twice that achieved with tPA treatment alone. Notably, under continuous perfusion at 10 mL/hr, MPCs maintained their penetration capability, and thrombolysis continued after magnetic retrieval of MPs. Collectively, these findings demonstrate that PMF-driven MPCs provide a simple, controllable strategy for enhancing intrathrombus drug transport and thrombolytic efficacy.