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<p>Photothermal therapy (PTT) holds transformative potential for precision cancer treatment, yet clinical translation remains constrained by the scarcity of molecularly defined, biocompatible, and efficiently NIR-absorbing photothermal agents (PTAs). Here we report a rational donor–acceptor–donor (D-A-D) framework that delivers ultrasmall organic PTAs with record photothermal conversion efficiencies (49.8%) and intrinsic immunogenic cell death (ICD) activity. The design exploits 6,7-diphenyl-[1,2,5]thiadiazolo[3,4-g]quinoxaline as a π-extended, multi-nitrogenated acceptor core flanked by trifluoromethyl groups to deepen the LUMO, while methoxylated triphenylamine donors intensify intramolecular charge-transfer and suppress radiative decay. Nanoprecipitation furnishes monodisperse nanoparticles that exhibit intense NIR-II absorption, exceptional photostability across five hyperthermic cycles, and lysosome-directed uptake. In vitro, single-dose FTPA NPs plus 808-nm laser irradiation trigger mitochondrial depolarization, G0/G1 arrest, and apoptosis in &gt; 70% of 4T1 cells while releasing abundant ATP and surface calreticulin—canonical ICD signals. A prophylactic vaccination model corroborates these molecular cues: mice primed with FTPA-NP-treated tumor cells reject contralateral challenge, achieving &gt; 90% long-term survival, expansion of cytotoxic CD8<sup>+</sup> T cells (≈ 70% activation), and suppression of Tregs (≈ 3%). No systemic toxicity or off-target pathology is observed. This study establishes a chemically tunable, metal-free PTA platform that synergizes thermal ablation with systemic anti-tumor immunity, providing a versatile scaffold for next-generation precision immuno-photothermal medicine.</p> Graphical Abstract <p></p>

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Molecularly sculpted NIR-II nano-igniter converts local photothermal heat into systemic antitumor vaccination

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月2日

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  • Qihang Ding,
  • Tingting Liu,
  • Chunbai Xiang,
  • Qian Wang,
  • Meiqin Li,
  • Yao Sun,
  • Ruiping Zhang

摘要

Photothermal therapy (PTT) holds transformative potential for precision cancer treatment, yet clinical translation remains constrained by the scarcity of molecularly defined, biocompatible, and efficiently NIR-absorbing photothermal agents (PTAs). Here we report a rational donor–acceptor–donor (D-A-D) framework that delivers ultrasmall organic PTAs with record photothermal conversion efficiencies (49.8%) and intrinsic immunogenic cell death (ICD) activity. The design exploits 6,7-diphenyl-[1,2,5]thiadiazolo[3,4-g]quinoxaline as a π-extended, multi-nitrogenated acceptor core flanked by trifluoromethyl groups to deepen the LUMO, while methoxylated triphenylamine donors intensify intramolecular charge-transfer and suppress radiative decay. Nanoprecipitation furnishes monodisperse nanoparticles that exhibit intense NIR-II absorption, exceptional photostability across five hyperthermic cycles, and lysosome-directed uptake. In vitro, single-dose FTPA NPs plus 808-nm laser irradiation trigger mitochondrial depolarization, G0/G1 arrest, and apoptosis in > 70% of 4T1 cells while releasing abundant ATP and surface calreticulin—canonical ICD signals. A prophylactic vaccination model corroborates these molecular cues: mice primed with FTPA-NP-treated tumor cells reject contralateral challenge, achieving > 90% long-term survival, expansion of cytotoxic CD8+ T cells (≈ 70% activation), and suppression of Tregs (≈ 3%). No systemic toxicity or off-target pathology is observed. This study establishes a chemically tunable, metal-free PTA platform that synergizes thermal ablation with systemic anti-tumor immunity, providing a versatile scaffold for next-generation precision immuno-photothermal medicine.

Graphical Abstract