ABSTRACT It is appealing yet challenging to design a single phototherapeutic agent integrating robust fluorescence emission and reactive oxygen species (ROS) yield. Here, we report the rational design and synthesis of a fluorophore (XSOTA) by linking a dibenzothiophene‐ S , S ‐dioxide acceptor to triphenylamine donor via a vinyl bridge. Detailed experimental studies and theoretical calculations reveal that XSOTA exhibits a hybridized local and charge transfer (HLCT) excited‐state character. This HLCT feature endows XSOTA with dual photophysical functionality: the locally excited (LE) state facilitates rapid radiative decay for high fluorescence quantum yield, while the charge‐transfer (CT) state promotes efficient intersystem crossing and ROS generation. Consequently, XSOTA achieves an outstanding fluorescence quantum yield of 89.2% in toluene, a large two‐photon absorption cross‐section of 7000 GM, and a high ROS yield of 56.3%. When encapsulated into biocompatible nanoparticles, XSOTA enables deep‐tissue two‐photon fluorescence imaging of mouse vasculature, achieving imaging depths of 320 µm in bladder vessels and 350 µm in liver tissue. Moreover, XSOTA‐based nanoparticles demonstrate effective imaging‐guided photodynamic therapy, significantly suppressing tumor growth without observable toxicity to major organs. These findings establish HLCT‐based fluorophores as promising dual‐function agents for image‐guided photodynamic cancer therapy.
Hu et al. (Fri,) studied this question.