An ONOO–/Viscosity-Sensitive and Mitochondria-Targeted Near-Infrared Fluorophore for Real-Time Tracking Mitophagy and Photodynamic Therapy of Cancer

Malignant tumors pose a serious threat to human life. Dual-functional agents with near-infrared fluorescence imaging and photodynamic therapy (PDT) activities have significant potential for synchronous cancer diagnosis and treatment due to their high sensitivity and noninvasiveness. In this study, based on the "organelle-targeted PDT" strategy, we developed a mitochondria-targeted and endoplasmic reticulum (ER)-located fluorescent probe, HCy-BA, which was constructed by the introduction of the phenylboronic acid group in the receptor component and the α-β unsaturated ester in the donor component of hemicyanine. HCy-BA enables near-infrared fluorescence imaging of ONOO- and viscosity with high sensitivity and specificity, and can effectively distinguish cancer cells from normal cells. Meanwhile, HCy-BA exhibits excellent 1O2 generation capacity, showing significant phototoxicity toward tumor cells and effective tumor suppression in tumor-bearing mice. Furthermore, HCy-BA allows real-time monitoring of mitochondrial autophagy during PDT, facilitating visualization of the treatment process and enabling real-time assessment of PDT. These results highlight the potential of HCy-BA in cancer diagnosis and treatment, offering new insights into the design of integrated molecular for diagnosis and therapy in the future.