Zeolitic imidazole framework-derived rich-Zn-Co3O4/N-doped porous carbon with multiple enzyme-like activities for synergistic cancer therapy

Abstract

Reactive oxygen species (ROS)-centered chemodynamic therapy (CDT) holds significant potential for tumor-specific treatment. However, insufficient endogenous H2O2 and extra glutathione within tumor microenvironment (TME) severely deteriorate the CDT's effectiveness. Herein, rich-Zn-Co3O4/N-doped porous carbon (Zn-Co3O4/NC) was fabricated by two-step pyrolysis, and applied to build high-efficiency nano-platform for synergistic cancer therapy upon combination with glucose oxidase (GOx), labeled Zn-Co3O4/NC-GOx for clarity. Specifically, the multiple enzyme-like activities of the Zn-Co3O4/NC were scrutinously investigated, including peroxidase-like activity to convert H2O2 to O2∙−, catalase-like activity to decompose H2O2 into O2, and oxidase-like activity to transform O2 to O2∙−, which achieved the CDT through the catalytic cascade reaction. Simultaneously, GOx reacted with intracellular glucose to produce gluconic acid and H2O2, realizing starvation therapy. In the acidic TME, the Zn-Co3O4/NC-GOx rapidly caused intracellular Zn2+ pool overload and disrupted cellular homeostasis for ion-intervention therapy. Additionally, the Zn-Co3O4/NC exhibited glutathione peroxidase-like activity, which consumed glutathione in tumor cells and reduced the ROS consumption for ferroptosis. The tumor treatments offer some constructive insights into the nanozyme-mediated catalytic medicine, coupled by avoiding the TME limitations.