Triggering Sequential Catalytic Fenton Reaction on 2D MXenes for Hyperthermia-Augmented Synergistic Nanocatalytic Cancer Therapy

The unique characteristics of a tumor microenvironment (TME) enable the development of new tumor-therapeutic modalities with high efficiency, biosafety, and tumor specificity. In this work, we report on the construction of photothermal-enhanced and nanocatalyst-enabled sequential catalytic reaction for TME-specific cancer therapy. This conceptual advance is achieved by engineering the surface of two-dimensional Ti3C2 MXene with two separate catalysts, including natural glucose oxidase (GOD) as glucose catalysts and superparamagnetic iron oxide nanoparticles (IONPs) as Fenton-reaction nanocatalysts. A sequential catalytic reaction is triggered by using GOD for catalyzing the tumor-overtaken glucose to generate large amounts of hydrogen peroxide molecules. Subsequently IONPs can catalyze the transformation of pregenerated hydrogen peroxide into large amounts of highly toxic hydroxyl radicals to kill the cancer cells subsequently in TME-enabled acidity condition. The two-dimensional (2D) Ti3C2 MXene matrix efficiently converts the near-infrared light into thermal energy to synergistically enhance the catalytic efficiency of this sequential catalytic reaction and therefore achieve the high synergistic cancer-therapeutic outcome, accompanied with the high biocompatibility of the constructed composite nanocatalysts. Both in vitro cancer-cell evaluation and in vivo tumor xenograft on nude mice with complete tumor eradication demonstrate the high synergistic efficiency of photothermal-enhanced sequential nanocatalytic cancer therapy. Therefore, this work substantially broadens the biomedical applications of 2D MXenes to nanocatalytic cancer therapy by enhancing the Fenton reaction-based nanocatalytic therapy via converting the near-infrared light into thermal energy and subsequently elevating the local Fenton-reaction temperature.