Dual-site co-valence cycling nanozyme for boosted cuproptosis and triple-modal photo-catalytic-immunotherapy via redox homeostasis imbalance

Disrupting redox homeostasis is a feasible strategy for reversing immunosuppressive tumor microenvironment. Herein, by coating copper selenide (Cu 2-x Se) on the surface of gold/molybdenum (AuMo), a AuMo@Cu 2-x Se nanozyme with triple-enzyme activities of glucose oxidase/glutathione peroxidase/peroxidase was reported for inducing immunogenic cell death (ICD) and cuproptosis, thereby enhancing antitumor immunotherapy. Benefiting from the reversible valence transition of Mo 6+ /Mo 4+ and Cu 2+ /Cu + , and the multi-enzyme activities, the reactive oxygen species (ROS) generation was enhanced, and the near-infrared II photothermal performance further promoted ROS generation, ultimately disrupting redox homeostasis. Moreover, by combining ROS storm and Cu 2+ transportion, the mitochondrial dysfunction was triggered, which activated ICD and cuproptosis, releasing damage related molecular patterns and regulating cuproptosis-related proteins. Under a 1064 nm laser irradiation, the AuMo@Cu 2-x Se nanozyme facilitated dendritic cells maturation, T cells infiltration, M1 macrophages polarization, and memory and regulatory T cells production. The developed AuMo@Cu 2-x Se nanozyme provided a feasible strategy of integrating cuproptosis and photo/catalytic/immunotherapy, significantly suppressing primary and metastatic tumors for breast cancer. A multifunctional dual-site co-valence cycling AuMo@Cu 2-x Se nanozyme for boosting cuproptosis and triple-modal photo-catalytic-immunotherapy via redox homeostasis imbalance. Download: Download high-res image (110KB) Download: Download full-size image