Deep-Red Multiple-Resonance B,N-Heteroarenes as Type I Photosensitizers for Fluorescence Imaging-Guided Photodynamic Therapy

Fluorescence imaging-guided type I photodynamic therapy (PDT) has shown significant potential for precise diagnosis and treatment in a hypoxic tumor microenvironment. However, the development of high-performance type I photosensitizers remains a formidable challenge due to inefficient intersystem crossing, short triplet-state photosensitization lifetime, low light harvesting efficiency, and severe aggregation-caused emission quenching. The conventional approach to designing photosensitizers is primarily based on the construction of donor-π-acceptor-type fluorophores, whereas new molecular building blocks are scarce yet significant. As a proof of concept, a multiple-resonance (MR)-structural type I photosensitizer featuring a three-dimensional paddle-wheel configuration is developed. Benefiting from the strong short-range charge transfer and robust molecular architecture with large steric hindrance, the MR photosensitizer exhibits a deep-red narrowband emission, small singlet-triplet energy gap, high molar extinction coefficient, and microsecond-scale triplet lifetime. Theoretical calculation and electrochemical and transient absorption spectroscopy demonstrate that multiple triplet-state photosensitization channels, efficient photogenerated charge-carrier separation, and long triplet lifetime of the MR photosensitizer facilitate the electron transfer to oxygen during the type I photodynamic reaction, resulting in producing the cytotoxic superoxide anion radical. In particular, the biocompatible MR-configured type I photosensitizer achieves superior antitumor performance toward in vivo fluorescence imaging-guided PDT for the first time.