Near‐infrared laser‐activated aggregation‐induced emission nanoparticles boost tumor carbonyl stress and immunotherapy of breast cancer

Abstract The induction of tumor carbonyl stress is reported to efficiently revert immune suppression in the tumor microenvironment and enhance cancer immunotherapy. However, low oxygen concentration due to inherent tumor hypoxia limits its catalytic effect. Herein, an injectable thermosensitive hydrogel system (named APH) is developed for co‐loading of near‐infrared (NIR) aggregation‐induced emission (AIE) nanoparticles and plasma amine oxidase (PAO) for boosting carbonyl stress and enhancing antitumor immunity. Upon 808 nm NIR laser irradiation, the AIE nanoparticles trigger a mild‐temperature (around 45°C) photothermal effect in the tumor site, which significantly relieves tumor hypoxia and promotes the catalytic effect of released PAO to inhibit the growth of Myeloid‐derived suppressor cells. Remarkably, the synergistic therapeutic effect of APH is verified through a significant inhibitory effect on the distant tumor, enhanced immune memory, and effective suppression of postoperative recurrence, rechallenge, and metastasis. Overall, the combined effect of AIE‐mediated photothermal therapy and carbonyl stress by APH upon NIR irradiation therapy can significantly activate cancer immunotherapy, making it a promising treatment approach for cancer treatment.