Self‐Amplifying AIE Probe for HClO‐Activatable Imaging and Antioxidative/Anti‐Inflammatory Therapy of Thoracic Aortic Dissection

Thoracic aortic dissection (TAD) is a highly lethal cardiovascular disease, yet its accurate diagnosis and effective treatment remain challenging due to poor imaging contrast and insufficient specificity. Leveraging the overexpressed reactive oxygen species (ROS) in TAD, we reported a hypochlorous acid (HClO)-activatable molecular probe DT-PZ. It enables two-stage self-amplifying fluorescence imaging (chemical activation and then physical aggregation) and light-independent therapy on a single chemical entity. The probe initially exhibits quenched fluorescence via photoinduced electron transfer (PET). Two pathways can turn on the fluorescence via chemical activation: (1) oxidation by HClO blocks PET and turns on the emission; (2) photo-triggered radicals generation of HClO (via chloride ions or myeloperoxidase) to activate neighboring probes, creating self-amplifying fluorescence. Upon accumulation at the lesion site, the physical aggregation caused by the aggregation-induced emission effect further amplifies the fluorescence signals. This two-stage fluorescence amplification mechanism enables TAD visualization within 2 min in vivo. For therapy, the phenothiazine scavenges excess ROS during non-illuminated periods, down-regulates the NF-κB/P65 signal pathway, and up-regulates eNOS and P-Akt expressions, protecting endothelial homeostasis and then improving murine survival from 50% to 90%. Collectively, DT-PZ synergizes self-amplifying fluorescence imaging with light-independent antioxidation/anti-inflammatory therapy, holding great promise for managing deep-seated cardiovascular diseases.