TME-Activated Nanofactory Orchestrate NIR-II Fluorescence/Photoacoustic Imaging-Guided Synergistic Chemodynamic/Photothermal Antitumor Therapy.

Triple-negative breast cancer (TNBC) is a highly aggressive and lethal malignancy with poor response to conventional therapeutic regimens. Thus, there is an urgent need to develop precision theranostic nanoplatforms that integrate accurate imaging guidance with synergistic therapeutic modalities. Herein, a novel responsive multifunctional Ag2S/MnO2@SiO2 (AMS) nanofactory was constructed for NIR-II fluorescence/photoacoustic (NIR-II FL/PA) imaging-guided synergistic chemodynamic/photothermal therapy (CDT/PTT) of TNBC. Leveraging the unique biochemical cues of the TME, AMS undergoes efficient degradation, leading to the rapid release of Ag2S and Mn2+ ions. The released Ag2S enables precise tumor localization via NIR-II FL/PA imaging, while simultaneously mediating efficient PTT upon 808 nm laser irradiation. Meanwhile, Mn2+ ions exhibit Fenton-like catalytic activity to convert endogenous H2O2 into highly toxic •OH for CDT, and the hyperthermia induced by PTT further accelerates the Fenton-like reaction to boost CDT efficacy, thus achieving highly efficient synergistic antitumor therapy. Collectively, the AMS nanofactory with favorable biocompatibility provides a promising strategy for precision theranostics of TNBC.