Dual RONS-responsive chemiluminescence-guided multimodal thrombolysis based on an aggregation-induced emission...

Carotid artery thrombosis carries a high risk of disability and mortality. Organic small molecules can be used to create personalized thrombosis theranostics in precision medicine. However, due to poor water solubility, instability, and competition in energy transfer mechanisms involved in imaging and treatment, the development of small-molecule probes with efficient therapeutic performance remains challenging. Herein, we report the first bimetallic, deep-penetrating aggregation-induced emission (AIE) cobalt-porphyrin-based nanoparticles (Co2Ir NPs) that enable the simultaneous "precise targeting, accurate treatment, and effective repair" of thrombosis. Co2Ir NPs undergo dual response to reactive oxygen and nitrogen species (RONS), releasing Co2Ir, which reacts with endogenous ONOO^- for chemiluminescence imaging, thereby allowing precise location of a thrombus. Co2Ir generates ¹O₂ and heat via photodynamic and photothermal therapy (PDT/PTT) under laser irradiation to dissolve thrombus surfaces, while sonodynamic therapy (SDT) drives the NPs into the thrombi to 8 mm penetration depth, with 82% thrombolysis efficiency without secondary embolism. Concurrently, Co2Ir NPs promote vascular reconstruction by upregulating HO-1 expression to exert antioxidant effects, and by downregulating pro-inflammatory factors like TNF-α and IL-6; this dual effect restores the thrombus site to normal. With its exceptional thrombolytic penetration and potent anti-inflammatory effects, this stimulus-responsive chemiluminescent probe holds great promise for the precise visualization and targeted treatment of thrombi.