ABSTRACT Type I photosensitizers capable of generating cytotoxic reactive oxygen species (ROS), with reduced oxygen dependence under photoirradiation, are regarded as a promising phototherapeutic approach for hypoxic solid tumors. Herein, based on the electron donor of 9‐phenyl‐carbazole (Cz) and the electron acceptor of anthraquinone (AQ), photosensitizer AQCzBF, which mainly produced superoxide anion–free radical (O 2 −• ), was developed for hypoxia‐resistant photodynamic therapy (PDT). Compared with AQCz without the boron difluoride chelation, photosensitizer AQCzBF showed not only redshifted absorption and pronounced intramolecular charge transfer (ICT) but also enhanced O 2 −• generation. Theoretical calculations revealed a smaller Δ E ST (0.13 eV), a larger SOC matrix element (7.80 cm −1 ), and more efficient intersystem crossing (ISC) for AQCzBF. Compared to AQCz NPs, AQCzBF NPs demonstrated significantly enhanced ROS generation, exhibiting 4‐fold higher total ROS and 7.16‐fold greater O 2 −• production. In vivo experiments verified the outstanding tumor suppression efficacy of AQCzBF NPs. This work presented an innovative molecular design of aminoanthraquinone photosensitizers through boron difluoride chelation to conquer tumor hypoxia for PDT.
Zhang et al. (Sun,) studied this question.