Thrombus Boring Microrobot Prepared by an Integrated Phase Separation and Interfacial Self-Assembly Process towards Thrombolysis

Abstract

The pathological formation of thrombi is the primary etiological factor of acute cardiovascular and cerebrovascular diseases, accounting for one-quarter of global fatalities. Traditional thrombolytic drugs are constrained by short half-life, low utilization, and severe complications. Inspired by the tunnel boring machine to excavate strata into small rocks, we reported urokinase plasminogen activator (uPA)-modified thrombus boring microrobots (uTBMs), prepared by a one-step integrated phase separation and interfacial self-assembly process, for effective thrombolysis. The uTBMs are composed of microspheres capped with dual-layered structures of magnetic nanoparticles (MNPs) and cilia nanostructures. In situ observation reveals the integrated phase separation and interfacial self-assembly process of the uTBMs within an emulsion droplet. The capped layer of MNPs allows for controllable motion and rotation behavior under the manipulation of a remote magnetic field. The uPA-modified cilia nanostructures grasp and degrade the fibrin network, synergizing with the uTBMs rotation to mechanically excavate blood cells from thrombus individually, achieving ~8.5-fold higher thrombolytic efficacy than uPA alone. This research demonstrates the feasibility of controllably fabricating and modifying complex-structured microrobots via the simple process towards the potential thrombus therapy.