NiFe-LDH-enhanced Ru single-atom catalysts anchored on MXenes for synergistic photothermal–nanocatalytic cancer therapy

Single-atom catalysts (SACs) have emerged as revolutionary agents in cancer treatment owing to their optimized atomic efficiency and highly tunable catalytic properties. Nonetheless, their clinical application is hindered by restricted stability, ineffective substrate adsorption, and subpar catalytic rates under physiological conditions. This study presents the rational design of a hybrid Ru single-atom nanozyme, based on a NiFe-layered double hydroxide (LDH) and coupled with an MXene (RuSA/NiFe-LDH-MXene), facilitating synergistic photothermal and catalytic tumor therapy. The NiFe-LDH matrix enables strong coordination with Ru atoms, enhancing their electronic configuration and serving a dual function of electron enrichment and substrate activation, while MXene nanosheets offer high conductivity and photothermal conversion. Our system demonstrates increased peroxidase-like activity, effectively promoting the decomposition of H₂O₂ and the depletion of glutathione, thus intensifying oxidative stress in tumor microenvironments. Upon NIR irradiation, RuSA/NiFe-LDH-MXene attains a significant temperature increase (∼52.7 °C at 0.5 W cm^-2 for 5 minutes) and has a high photothermal conversion efficiency (∼46.8%). The nanozyme exhibits approximately a 2.8-fold increased catalytic velocity (<i>V</i>_max) for H₂O₂ breakdown and a roughly 1.6-fold enhanced production of hydroxyl radicals in comparison with RuSA@MXene. <i>In vivo</i> investigations revealed enhanced tumor ablation, with the RuSA/NiFe-LDH-MXene + NIR group attaining a tumor inhibition rate of 91.7% without systemic toxicity. This study emphasizes the essential function of LDH coordination in stabilizing Ru single atoms and adjusting their catalytic microenvironment, thereby creating a solid foundation for advanced nanocatalytic cancer treatments.