A-D-A-structured phototheranostics for NIR fluorescence imaging guided Type I/II photodynamic and photothermal therapy of tumor.

Here, we report a compact, single-component nanotheranostic platform-4TIC nanoparticles-formed by molecular self-assembly of an A-D-A-structured near-infrared (NIR) photosensitizer (4TIC) and DSPE-PEG-NH2. Upon single-wavelength (808 nm) laser irradiation, 4TIC NPs enable simultaneous NIR fluorescence imaging, efficient photothermal therapy, and Type I and Type II photodynamic activity. In vitro, 4TIC NPs enter cells via macropinocytosis and clathrin-mediated endocytosis, localizing in lysosomes. They exhibit excellent biocompatibility in the dark but induce mitochondrial depolarization and apoptosis upon irradiation. In vivo, 4TIC NPs delineate tumor margins via NIR fluorescence and synergistically suppress tumor growth through combined photothermal and photodynamic effects without systemic toxicity, offering a promising integrated strategy for precise and effective cancer phototherapy.