Light-Driven ESIPT-Based Anthraquinone Analogues for Synergistic Fluorescent Self-Reporting and Photodynamic Therapy of Malignant Tumors

The intelligent integration of intervention and self-reporting signals from photosensitizers (PSs) in living organisms remains a challenge. Herein, we developed two anthraquinone-based PSs (1H-D1 and 1H8H-D1) through polymerization and end-group modification approaches, which exhibited weak fluorescence due to disruption of the excited-state intramolecular proton transfer (ESIPT) process. These dimer PSs exhibited mitochondrial targeting and released monomer natural products─anthraquinone derivatives (1H and 1H8H) under light irradiation. The released monomers restored ESIPT fluorescence and effectively generated O₂^•- via the type-I reaction under continuous light irradiation, thereby suppressing the growth of tumor cells. Notably, in vivo experiments showed that 1H-D1 significantly inhibited tumor growth (<i>V</i>_light/<i>V</i>_control ≈ 0.24). At the same time, the fluorescence intensity of 1H-D1 was greatly enhanced, providing excellent guidance on the treatment outcome. It can be seen that this dual-effect synergy strategy offers a promising approach for designing natural product-based self-reporting PSs with enhanced therapeutic and diagnostic capabilities.