Quinoid-Engineered Small-Molecule Photothermal Agents Ignite Deep-Tissue Tumor Photothermal-Immunotherapy Driven by 1064 nm Light

Developing small-molecule photothermal agents (PTAs) with strong absorption in the NIR-II window (1000-1700 nm) remains a significant challenge for effective photothermal therapy (PTT) of deep-seated tumors. Here, a quinoidal engineering strategy is presented to construct a 1064 nm-excitable small-molecule PTA, termed BPT-FNC, which features a highly quinonized naphthalenedione-based terminal group, an open-shell singlet diradical ground state, and thermally accessible triplet states. These electronic characteristics endow BPT-FNC with pronounced NIR-II absorption, promoting efficient nonradiative decay and high photothermal conversion efficiency. Under 1064 nm laser irradiation at clinically permissible power densities, BPT-FNC nanoaggregates enable effective deep-tissue PTT. Notably, it also triggers pyroptosis and promotes the release of immunogenic damage-associated molecular patterns (DAMPs), thereby inducing immunogenic cell death (ICD) and stimulating systemic anti-tumor immune responses. This work showcases a rational molecular design paradigm that integrates quinoidal structure, NIR-II photothermal functionality, and immune activation, offering a promising platform for synergistic photothermal-immunotherapy in precision cancer treatment.