Photothermal-Amplified Enzyme-Catalyzed Cascade Based on Gold Nanoparticle-Decorated MXene Overcoming H2O2 Barrier for Synergistic Tumor Therapy

Abstract MXenes have emerged as promising two-dimensional nanomaterials for cancer nanomedicine owing to their tunable surface chemistry, strong photothermal response, and favorable biocompatibility. Herein, we develop a gold nanoparticles-decorated MXene nanoplatform (Au@Mo2TiC2Tx-PEG) for synergistic photothermal and catalytic tumor therapy. The nanoplatform is constructed by anchoring Au nanoparticles onto Mo2TiC2Tx nanosheets, followed by polyethylene glycol modification to improve physiological stability and biocompatibility. The as-prepared Au@Mo2TiC2Tx-PEG exhibits strong near-infrared absorption with a photothermal conversion efficiency of 39.8%, enabling effective photothermal therapy under 808 nm laser irradiation. Notably, this nanoplatform possesses intrinsic glucose oxidase (GOx)-like and peroxidase (POD)-like activities, which initiate a cascade catalytic reaction within the tumor microenvironment. Glucose oxidation-mediated H2O2 generation, which subsequently converts into highly cytotoxic reactive oxygen species, while simultaneously depleting intracellular glutathione disrupts tumor redox homeostasis. The integrated catalytic and photothermal effects synergistically enhance oxidative stress, promote tumor cell apoptosis, and improve therapeutic efficacy. Both in vitro and in vivo studies reveal that Au@Mo2TiC2Tx-PEG effectively suppresses tumor progression, achieving a tumor inhibition rate of 94% under 808 nm laser irradiation with minimal systemic toxicity. These findings demonstrate the potential of the MXene-based nanoplatform to integrate catalytic metabolism regulation and photothermal activation, providing a powerful strategy for precision cancer therapy.