MXene-Based Nanosheets Reverse Tumor Hypoxia to Amplify Triple-Mode Cancer Therapy.

Despite MXene's good biocompatibility and photothermal properties, its poor stability in physiological environments and non-specific characteristics still pose potential risks and limit its application in the anti-tumor field. Herein, an efficient cascade catalytic system is designed by loading folic acid and bovine serum albumin-modified manganese dioxide (MnO2) onto MXene nanosheets, improving the dispersibility of MXene in physiological environments and endowing it with active targeting capability for folate receptor-overexpressing tumors and O2 regeneration capacity. Glucose oxidase (GOx) and L-arginine (L-Arg) are sequentially loaded onto MXene to obtain a cascade catalytic system for anti-cancer applications. MXene can be used to mediate near-infrared light-based photothermal therapy. GOx consumes intracellular glucose and generates hydrogen peroxide (H2O2), which can further oxidize L-Arg to generate nitric oxide and finally achieve synergy between starvation therapy and gas therapy. MnO2 decomposes excess H2O2 and generates O2, thus alleviating hypoxic inhibition of the tumor microenvironment and enhancing the effect of starvation therapy. A series of in vivo and ex vivo experiments demonstrates that the developed cascade catalytic system has much better anti-cancer effects with low toxicity and side effects, and successfully synergizes starvation/gas/photothermal therapies, which represents a novel, green, and promising strategy for cancer treatment without any chemotherapeutics.