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

Abstract

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.