Endogenous near-infrared chemiluminescent manganese ion-driven porphyrin supramolecular platform for the theranostics of thrombosis and ischemic stroke.

Ischemic stroke (IS) is a cerebrovascular disease with high mortality and disability rates. Effective treatment of IS remains limited by insufficient lesion identification, incomplete thrombus elimination, and progressively aggravated reperfusion injury, thus highlighting the urgent need for an integrated strategy that bridges precise imaging, efficient thrombolysis, and neuroprotection. This study developed a nanoplatform (Mn-Ce6@R NPs) through a simple one-pot coordination-driven self-assembly process, featuring facile preparation and good reproducibility. The coordination of Mn2+ modulated the aggregation state and photophysical behaviour of Ce6, thereby enhancing its ONOO--responsive near-infrared chemiluminescence output and enabling precise imaging of thrombotic lesions and cerebral ischemia/reperfusion sites with a tissue penetration depth >10 mm. Under 689 nm laser irradiation, this platform synergistically triggered photothermal and photodynamic effects to achieve efficient thrombolysis. Meanwhile, its Mn-related enzyme-mimetic activity continuously scavenged RONS, alleviated inflammation, and exerted neuroprotective effects. The resulting nanoplatform exhibited excellent stability and high Ce6 loading capacity, with an approximately 77-fold enhancement in chemiluminescence signal toward ONOO-. It also achieved an in vitro thrombolysis efficiency of 74.0% and significantly restored blood perfusion in vivo, while reducing cerebral infarct volume. Collectively, this study establishes a sequential nanotheranostic strategy for the continuous pathological progression of IS and provides a translationally promising approach for real-time monitoring, precise thrombolysis, and post-reperfusion protection.