“Four‐in‐One” Nanozyme and Natural Enzyme Symbiotic System of Cu_2‐xSe−GOx for Cervical Cancer Therapy

Abstract

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 SeÀ 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 SeÀ GOx could induce significant ROS accumulation at the tumor regions, thus providing a potential approach for the treatment of cervical cancer.

Dual-Functional Nanoplatform Based on Bimetallic Metal–Organic Frameworks for Synergistic Starvation and Chemodynamic Therapy

“…In case of insufficient glucose supply, tumor growth is significantly inhibited. Accordingly, starvation therapy relying on glucose consumption is a potential strategy for oncology treatment. − Glucose oxidase (GOx) has been reported to inhibit tumor growth by catalyzing the production of gluconic acid and hydrogen peroxide from glucose; it can thus be used to consume glucose and cut off the energy supply to tumor cells. − Moreover, hydrogen peroxide production by GOx can further improve the efficiency of CDT, providing a model of synergistic treatment. − In a previous study, a tumor-targeted cascade bioreactor for synergistic starvation and photodynamic therapy (PDT) was constructed by inserting glucose oxidase (GOx), catalase (CAT), and chlorinated e6 (Ce6) into human serum albumin (HSA) assembly molecules . Further, Fe 3 O 4 @ZIF-8/GOx@MnO 2 multilayered core–shell nanostructured hybrid nano-enzyme was studied for the synergistic treatment of multiple modalities .…”

Tri-element nanozyme PtCuSe as an ingenious cascade catalytic machine for the amelioration of Parkinson’s disease-like symptoms

“…Selenium is an important cofactor in GSH-PX and plays an unmatched role in catalyzing the redox reaction of reducing glutathione (GSH) with peroxide ( Dringen et al, 2015 ; Peter et al, 2015 ; Sun et al, 2016 ). Therefore, it is an important cellular free radical scavenger in introducing selenium into PtCu nanozymes, which can improve biocompatibility and reduce biological toxicity ( Huang et al, 2017 ; Hu et al, 2022 ). Therefore, PtCuSe shows great potential in catalyzing the generation of oxygen from over-produced hydrogen peroxide in cells, which reduces the damage caused by hydrogen peroxide to tissues and cells, solves the problem of accumulation of excess free radicals in order to reduce the intracellular ROS level and alleviate neuronal degeneration damage, and solves the problem of apoptosis in neurons in PD to a large extent ( Ding et al, 2021 ; Xue et al, 2022 ; Yu et al, 2022 ).…”