Photosensitizers showing aggregation‐induced emission (AIE) that respond to local viscosity and target specific organelles are highly desirable for precise photodynamic therapy (PDT) and mechanistic imaging within biosystems. Here, we report a viscosity‐responsive AIEgen, called TQ‐A1, that selectively accumulates in mitochondria and enables real‐time visualization of mitochondrial fragmentation while delivering efficient PDT. TQ‐A1 has a donor– π –acceptor architecture with pronounced AIE characteristics, and its deep‐red emission is significantly enhanced in viscous or aggregated states. Single‐crystal analysis and quantum‐chemical calculations show that aggregation restricts intramolecular motion, lowers the reorganization energy, and suppresses nonradiative decay. Under light irradiation, TQ‐A1 generates both type I and type II reactive oxygen species, exhibits potent photocytotoxicity toward cancer cells, and displays excellent mitochondrial colocalization. Time‐lapse fluorescence imaging reveals a ROS‐driven morphological evolution of mitochondria from filamentous networks to granules, donuts, and compact clusters. In a HeLa xenograft model, the TQ‐A1‐mediated PDT markedly inhibits tumor growth without obvious systemic toxicity. These findings identify acetal‐tuned, viscosity‐responsive AIE photosensitizers as a useful platform for targeted mitochondrial imaging, real‐time tracking of organelle dynamics, and effective photodynamic tumor therapy.
Zuo et al. (Sun,) studied this question.