A “simple” phototheranostic agent for high-performance type I photodynamic and photothermal synergistic cancer therapy

Synergistic type I photodynamic therapy (PDT) and photothermal therapy (PTT) offer a prospective approach to address the challenges posed by tumor hypoxia and heterogeneity, thereby achieving enhanced antitumor therapeutic outcomes. However, developing simple synthetic phototheranostic agents with efficient type I reactive oxygen species (ROS) generation and effective photothermal conversion is still a significant task. In this study, fluorenone (FO), known for its potent electron-withdrawing properties, was conjugated with the rotor-type electron-donating triphenylamine (TPA) to construct a donor–acceptor–donor (D–A D) structural aggregation-induced emission (AIE) photosensitizer ( TPAF ), followed by the formation of nanoparticles (NPs) TPAF CNPs via self-assembly with DSPE-mPEG 2000 -cRGD and DSPE-mPEG 2000 . The TPAF CNPs effectively integrated efficient type I ROS with exceptional photothermal conversion capability. The fundamental photophysical and photochemical mechanisms underlying the synergistic effects of type I photodynamic and photothermal processes were explored through experimental and theoretical methods. In vitro and in vivo experiments showed that TPAF CNPs exhibited excellent photostability, good biocompatibility, enhanced tumor targeting, and outstanding synergistic type I PDT/PTT effects, achieving substantial antitumor therapeutic efficacy with a single injection and one laser irradiation. Overall, this study contributes to the growing field of high-performance type I PDT/PTT nanomedicine for synergistic phototheranostic applications.