A Radical‐Stabilized Ternary Cocrystal Platform for NIR‐II‐Triggered Gas‐Sensitized Mild Photothermal Immunotherapy

Organic charge‐transfer cocrystals hold great promise for photothermal therapy, yet their application is often constrained by low conversion efficiency and narrow absorption, particularly in the second near‐infrared (NIR‐II) window. Herein, we develop a ternary donor–acceptor cocrystal (TTP) by incorporating pyrene as a molecular blocker to broaden absorption, stabilize radicals, and enhance molecular motion, achieving a NIR‐II photothermal conversion efficiency of 48.4%. TTP is further co‐assembled with the thermosensitive nitric oxide (NO) donor, BNN6, and hyaluronic acid (HA) to form TTP‐BNN6@HA nanoparticles (NPs). Under 1064 nm laser irradiation, TTP‐BNN6@HA NPs generate localized mild hyperthermia and trigger controlled NO release, which synergistically induces immunogenic cell death, inhibits heat‐shock‐protein expression to overcome thermal resistance, and promotes dendritic cell maturation. In murine breast cancer models, local treatment with TTP‐BNN6@HA NPs under NIR‐II laser irradiation not only potently suppresses primary and distant tumor growth but also activates a systemic immune response, leading to a significant reduction of lung metastasis. Transcriptomic analysis confirms the downregulation of metastasis‐related pathways and the upregulation of immune activation. Collectively, this work presents a supramolecular strategy for engineering high‐performance organic photothermal agents and establishes a potent synergistic platform for mild photothermal‐gas immunotherapy against tumor metastasis.