Anchoring Ru single-atoms on MXene achieves dual-enzyme activities for mild photothermal augmented nanocatalytic therapy

Single-atom catalysts with abnormally high catalytic activity have garnered extensive attention and interest for their application in tumor therapy. Despite the advancements made with current nanotherapeutic agents, developing efficient systems for cancer treatment remains challenging due to low activity, uncontrollable behavior, and nonselective interactions. Herein, we have constructed Ru single-atom-anchored MXene nanozymes (Ru-Ti₃C₂T_<i>x</i>-PEG) with a mild photothermal effect and multi-enzyme catalytic activity for synergistic tumor therapy. Ru single atoms anchored on the surface of MXene nanosheets not only facilitate multi-enzyme catalytic activity but also amplify the photothermal performance owing to the localized surface plasmon resonance effect. The Ru single atoms could decompose H₂O₂ into toxic hydroxyl radicals (•OH) in response to the tumor microenvironment (TME) for enzyme catalytic therapy, and the heat produced by the nanozyme under near-infrared laser excitation enhanced the •OH generation yield. Moreover, the nanozyme exhibited oxygen formation and glutathione depletion capability in cancer cells, thereby regulating the TME and accelerating the •OH levels. The <i>in vitro</i> and <i>in vivo</i> studies in this work confirm that the two-dimensional Ru single-atom-anchored MXene nanozyme has an extraordinary tumor growth inhibition effect, thus presenting a rational therapeutic strategy for tumor ablation through the synergistic effect of photothermal activity and heat-promoted enzymatic catalysis.