A Dual‐Functional Photosensitizer for Ultraefficient Photodynamic Therapy and Synchronous Anticancer Efficacy Monitoring

A dual‐functional photosensitizer that demonstrates exceptional photodynamic therapy (PDT) efficacy while simultaneously self‐monitoring the therapeutic response in real time is reported here. Possessing an ultrahigh 1O2 quantum yield of 98.6% in water, the photosensitizer TPCI can efficiently induce cell death in a series of carcinoma cells (IC50 values less than 300 × 10−9 m) upon irradiation with an extremely low fluence (460 nm, 4 mW cm−2 for 10 min). In addition, TPCI can self‐monitor cell death in real time. It is weakly fluorescent in living cells before irradiation and lights up the nuclei concomitantly with cell death during PDT treatment by binding with chromatin to activate its aggregation‐induced emission, attributed to its strong binding affinity with DNA. In vivo studies using mouse models bearing H22 and B16F10 tumor cells validate the ultraefficient PDT efficacy of TPCI as well as the precise real‐time noninvasive readout of the tumor response from the beginning of cancer treatment. The dual‐functional TPCI serves as an excellent candidate for single‐agent photodynamic theranostics, and this work represents a new paradigm for the development of molecules with multiple intrinsic functions for future self‐reporting medical applications. The first small molecule photosensitizer that integrates superior photodynamic therapy efficacy and an inherent real‐time noninvasive readout of tumor response during the cancer treatment is designed and synthesized. Possessing a high 1O2 quantum yield and strong binding affinity with DNA, the photosensitizer TPCI induces instantaneous cell damage and self‐illuminates the nuclei during the cell death, offering a great opportunity for single‐molecule photodynamic theranostics.