Reasonable design of NIR AIEgens for fluorescence imaging and effective photothermal/photodynamic cancer therapy

The development of a multifunctional single molecule phototherapeutic agent with excellent fluorescence imaging, photothermal therapy and photodynamic therapy at the same time is still a challenging task, which mainly arises from the low absorbance of the molecule, and the complexity of energy dissipation and molecular design. Herein, four donor-acceptor (D-A) compounds were synthesized by linking triphenylamine (TPA), thiophene/thieno[3,2-b]thiophene and different cyano acceptor structures. In this design, we propose a molecular design strategy to redshift absorption and increase the molar extinction coefficient (ε) by enhancing electron-withdrawing acceptors and enlarging the π-conjugation plane unit. Due to the twisted structure of TPA, these compounds exhibit aggregation-induced emission (AIE) characteristics. Notably, these AIEgens have long emission wavelengths, excellent photostability, biocompatibility, photothermal stability and singlet oxygen (¹O₂) generation performance. Among them, the photothermal conversion efficiency of a compound (named TCF-SS-TPA NPs) can reach 84.5%. Cellular internalization and therapy showed that TCF-SS-TPA NPs have good biocompatibility, excellent cell bioimaging and cancer phototherapy capabilities in vitro. This study will stimulate the molecular design of multifunctional phototherapeutics to realize effective synergistic cancer therapy.