Multifunctional Hybridized Local and Charge-Transfer Small Molecular Fluorophore for Imaging-Guided Photodynamic...

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.