NIR light activates upconverting nanoparticles/ZnxMn1−xS core–shell nanoparticles for improved breast cancer treatment

Multimodal combined therapy constitutes an ideal strategy for the treatment of primary tumors and the suppression of distant metastatic tumors. In this study, a 4T1 cell membrane-coated UCNPs@Zn_xMn_1-xS (TUC@ZMS) nanoplatform is designed for synergistic photodynamic (PDT), chemodynamic (CDT), gas, and immune-based cancer therapy. The 4T1 cell membrane coating enhances tumor-targeting specificity, while TUC@ZMS, under 980 nm near-infrared (NIR) light activation, generates singlet oxygen (¹O₂) for PDT and induces reactive oxygen species (ROS) via CDT to trigger tumor cell apoptosis. The released Mn⁴⁺ ions are reduced to Mn²⁺in situ, depleting intracellular glutathione (GSH) and further enhancing the efficacy of both PDT and CDT. Notably, PDT also promotes immunogenic cell death (ICD), while Mn²⁺ and H₂S activate the cGAS-STING pathway, inducing systemic immune responses characterized by infiltration of CD8⁺ T cells and NK cells. This multimodal therapeutic strategy targets primary breast tumors while effectively inhibiting distant lung metastases. Overall, TUC@ZMS demonstrates significant potential as a multifunctional nanoplatform for synergistic cancer treatment and immune activation.