NIR-II Light-Activated Nanoplatform for Synergistic Photothermal and H₂S-Mediated Thrombolysis.

Abstract

Occlusive thrombi within blood vessels are a primary cause of life-threatening cardiovascular diseases, which continue to pose significant global health challenges. Here, we report a polymer nanoplatform that integrates near-infrared II (NIR-II) light-triggered photothermal thrombolysis with intrinsic antithrombotic functionality. A novel semiconducting polymer, featuring intense NIR-II absorption and exceptionally high photothermal conversion, is rationally engineered to enable rapid and localized light-to-heat thrombolysis. A thermosensitive hydrogen sulfide (H₂S) donor is also incorporated, generating multifunctional "nanosweepers" that combine synergistic photothermal and gas-mediated thrombolytic activity. The formulation is further functionalized with bis-serotonin groups, which confer myeloperoxidase- and hydrogen peroxide-responsive thrombus-targeting capability, ensuring selective accumulation and site-specific therapy. This agent possesses robust NIR-II absorption, high photothermal conversion efficiency (77.2%), and pronounced thrombus-specific enrichment. Importantly, the combination of localized photothermal heating and on-demand H₂S release enable rapid, near-complete thrombolysis in both carotid and lower-limb arterial thrombosis models, achieving almost full restoration of blood flow. This work establishes a versatile and highly efficient strategy that integrates precise NIR-II photothermal conversion with H₂S-mediated redox regulation, providing a promising platform for site-specific multimodal synergistic treatment of life-threatening thrombotic disorders. The findings offer new insights into the design of multifunctional, precision therapeutics for vascular disease management.