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

Graphical The nanozyme@natural enzyme symbiotic system of Cu 2- x Se−GOx exhibited prominent “four-in-one” cascaded catalytic enzyme activities including catalase, peroxidase, glutathione oxidase and glucose oxidase. The ingenious Cu 2- x Se−GOx could significantly induce the accumulation of reactive oxygen species (ROS) at tumor regions; this results in a tumor microenvironment (TME)-activated “four-in-one” enzyme cascade that is lethal to cervical cancer. All in all, Cu 2- x Se−GOx can act as a high-performance and safe bioactive material for cancer treatment. 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 Cu 2- x Se−GOx for TME-triggered cascaded catalytic enhanced cancer treatment. In response to unique TME, Cu 2- x Se with catalase activity could effectively catalyze over-expressed H 2 O 2 in cancer cells into O 2 . Subsequently, the glucose oxidase (GOx) could deplete intracellular glucose with the assistance of O 2 ; this not only achieves starvation therapy, but also regenerates H 2 O 2 to boost the generation of highly cytotoxic . OH due to the peroxidase activity of Cu 2- x Se. Moreover, although the free-radical scavenger glutathione (GSH) is overexpressed in tumor cells, Cu 2- 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 Cu 2- x Se−GOx could induce significant ROS accumulation at the tumor regions, thus providing a potential approach for the treatment of cervical cancer.