“Four‐in‐One” Nanozyme and Natural Enzyme Symbiotic System of Cu2‐xSe−GOx for Cervical Cancer Therapy

Cervical cancer, as a common malignant tumor of the reproductive system, seriously threatens women's life and health, and is difficult to be cured by traditional treatments, such as surgery, chemotherapy and radiotherapy. Fortunately, tumor microenvironment (TME)-activated catalytic therapy with high efficiency and reduced off-target toxicity has emerged as a novel treatment model. Herein, we designed a "four-in-one" nanozyme and natural enzyme symbiotic system of Cu2-x Se-GOx for TME-triggered cascaded catalytic enhanced cancer treatment. In response to unique TME, Cu2-x Se with catalase activity could effectively catalyze over-expressed H2 O2 in cancer cells into O2 . Subsequently, the glucose oxidase (GOx) could deplete intracellular glucose with the assistance of O2 ; this not only achieves starvation therapy, but also regenerates H2 O2 to boost the generation of highly cytotoxic . OH due to the peroxidase activity of Cu2-x Se. Moreover, although the free-radical scavenger glutathione (GSH) is overexpressed in tumor cells, Cu2-x Se with glutathione oxidase activity could effectively consume GSH for enhanced ROS production. Thus, the "four-in-one" nanozyme@natural enzyme symbiotic system of Cu2-x Se-GOx could induce significant ROS accumulation at the tumor regions, thus providing a potential approach for the treatment of cervical cancer.