Dual-Functional Nanoplatform Based on Bimetallic Metal–Organic Frameworks for Synergistic Starvation and Chemodynamic Therapy
Yu Xiao, Fuxuan Lai, Mengran Xu, Danning Zheng, Yi Hu, Ming Sun, Na Lv
Abstract
Tumor microenvironment (TME)-responsive chemodynamic therapy (CDT) mediated by nanozymes has been extensively studied in oral squamous cell carcinoma. However, the low catalytic efficiency due to insufficient H 2 O 2 in the TME is still a major challenge for its clinical translation. Herein, we present an antitumor nanoplatform based on a Mn–Co organometallic framework material (MnCoMOF), which shows peroxidase-like (POD-like) activity, loaded with glucose oxidase ( [email protected] ), demonstrating the ability of H 2 O 2 self-supply and H 2 O 2 conversion to toxic hydroxyl radicals. The encapsulated GOx efficiently catalyzes glucose into gluconic acid and H 2 O 2 at the tumor site, which can cut off the energy supply to inhibit tumor growth and produce a large amount of H 2 O 2 and acid to compensate for their lack in the tumor microenvironment. The POD-like activity of MnCoMOF can convert H 2 O 2 into hydroxyl radicals and eliminate tumor cells. The nanoplatform exhibits enhanced tumor cell cytotoxicity in a high-glucose medium compared with a low-glucose medium, illustrating sufficient generation of H 2 O 2 from glucose by GOx. The in vivo results indicate that [email protected] has excellent antitumor efficacy and can remodel the immune-suppressive tumor microenvironment. In conclusion, the [email protected] nanoplatform possesses dual enzymatic activities, i.e., POD-like and glucose oxidase, to achieve improved tumor-suppressive efficiency through synergistic starvation and chemodynamic therapy, thus providing a new strategy for the clinical treatment of oral cancer.