NIR‐II Light‐Activated Nanoplatform for Synergistic Photothermal and H 2 S‐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 (H 2 S) 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 H 2 S 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 H 2 S‐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.