Type I photodynamic therapy guided by NIR-II fluorescence imaging is used for the treatment of triple-negative breast cancer

To address the limitations of photodynamic therapy (PDT), such as its oxygen dependence and insufficient tissue penetration, this study constructed a type-I photosensitizer with aggregation-induced emission (AIE) characteristics, named DHSTPA, based on a donor-π bridge-acceptor (D-π-A) structure, as well as its corresponding nanoparticles (DHSTPA NPs). DHSTPA NPs exhibit near-infrared absorption and second near-infrared (NIR-II) window fluorescence emission. Under 660 nm laser irradiation, they can efficiently generate reactive oxygen species (ROS), including superoxide anion and hydroxyl radicals. Cellular experiments demonstrated that DHSTPA NPs could be effectively internalized by 4T1 cells and localized in lysosomes. Upon irradiation, they induced cell death primarily via a type-I photodynamic mechanism. In vivo experiments revealed that DHSTPA NPs accumulated well at the tumor site. Following light exposure, they significantly inhibited tumor growth and induced necrosis and apoptosis, with no observed significant systemic toxicity. These results indicate that DHSTPA NPs represent a promising photosensitizing system with NIR-II emission, efficient type-I photodynamic activity, and favorable biosafety.