Non-Fused Ring A-D-A-Type Dyes for Near-Infrared II Fluorescence Imaging Guided Phototherapy and Immune Activation of Tumour

Phototherapy has gained considerable attention in cancer treatment. Molecules with pronounced near-infrared (NIR) absorption are particularly advantageous for laser-induced phototherapy, as their NIR absorption enables deep tissue penetration while minimizing incidental damage to healthy tissues. In this study, we rationally designed and synthesized a non-fused ring A-D-A-type dye (T8IC4F) exhibiting both NIR absorption and fluorescence properties. Through self-assembly of T8IC4F with DSPE-PEG-NH 2 , water-dispersible nanoparticles (NPs) designated as C4@PEG were fabricated. The resulting C4@PEG NPs exhibit NIR absorption and NIR-II fluorescence properties and demonstrate significant therapeutic efficacy. Upon 808 nm laser irradiation (1 W·cm −2 ), these NPs exhibit a singlet oxygen ( 1 O 2 ) quantum yield of 25.9% and a photothermal conversion efficiency of 61%. These properties enable them to mediate both photodynamic and photothermal therapy, leading to robust antitumor efficacy. Moreover, C4@PEG NPs induce immunogenic cell death, facilitate the release of tumor antigens, and activate an antitumor immune response. These findings suggest that C4@PEG NPs could be applied in cancer phototherapy and immunotherapy.