Engineering Ru-Fe dual-atom catalysts for multi-enzyme ROS amplification and NIR-II photothermal therapy

Nanocatalytic therapies using reactive oxygen species have shown promise for treating cancer; however, the efficacy of these therapies is often limited due to poor ROS generation, limited availability of endogenous hydrogen peroxide, and rapid replenishment of endogenous antioxidants in the tumor microenvironment. In this publication, we present the first heteronuclear dual-atom Ru-Fe nanozyme anchored onto a g-C₃N₄ matrix (Ru-Fe DA@NC) that combines multi-enzyme-like catalytic activity with effective NIR-II photothermal conversion for improved cancer therapy. The spatially organized Ru-N₄ and Fe-N₄ sites provide an opportunity for complementary catalytic functions resembling the activities of oxidase-, peroxidase-, catalase- and glutathione oxidase-like enzymes, which allows for continual amplifying of ROS production via simultaneous catalytic pathways. The Ru sites impart redox cycling and NIR-II photothermal responsiveness, while the Fe sites promote Fenton-like ROS production. The photothermal component also enhances the catalytic efficiency during 1064 nm irradiation which results in a greater quantity of ROS produced and faster depletion of intracellular glutathione; reliably disrupting tumor redox homeostasis. In vitro and in vivo data suggest that Ru-Fe DA@NC provides a significant level of tumor cell death and achieves > 90% tumor growth inhibition at low metal concentrations while showing preliminary in vitro and hemocompatibility profiles under the tested conditions. The findings presented here highlight the engineering potential of heteronuclear Ru-Fe dual atoms as a means to overcome the limitations of available ROS in tumors.