NIR‐Driven Nanomotors Integrating With Platelet‐Thylakoid Hybrid Membranes for Synchronized Thrombolysis and Vascular Remodeling

Abstract

Abstract The pathological interplay of oxidative stress, inflammation, and thrombosis driven by endothelial injury creates a self‐perpetuating cycle that undermines conventional thrombolytic therapies. Herein, near‐infrared (NIR)‐responsive nanomotors are constructed by integrating thylakoid and platelet membranes on strontium‐doped mesoporous polydopamine nanoparticles (PSr@PT NPs), which enables synchronized thrombus dissolution and vascular microenvironment restoration. Following intravenous administration, PSr@PT nanomotors exhibited preferential accumulation within thrombi and were internalized by injured endothelial cells. Meanwhile, thylakoid‐embedded catalase catalyzed endogenous hydrogen peroxide to oxygen, which can not only suppress oxidative damage and neutralize to disrupt platelet‐endothelium interactions, but also generate self‐propulsive forces via gas propulsion, facilitating deep intrathrombus penetration of PSr@PT NPs. Proteomic analysis revealed that PSr@PT NPs inhibited thrombosis progression by downregulating platelet activation and modulating JAK‐STAT/PI3K‐Akt signaling pathways, thereby reducing inflammation and fostering angiogenesis. Local NIR irradiation induced mild photothermal conversion of PSr@PT NPs, which softened fibrin networks, enhanced intrathrombus infiltration, and accelerated localized thrombolysis. In both FeCl 3 ‐induced murine carotid thrombosis and arachidonic acid‐induced zebrafish thrombosis models, the PSr@PT NPs effectively resolved occlusions and restored endothelial function. By coupling ROS‐powered propulsion with adaptive microenvironment remodeling, this nanomotor transcends conventional 1D clot lysis, offering a dynamic strategy to prevent thrombosis recurrence and accelerate functional vascular recovery.