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

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 FeCl₃-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.