Dual isolated bimetal single-atom catalysts for tumor ROS cycle and parallel catalytic therapy

The application of emerging nanocatalytic drugs in tumor therapy mainly depends on reactive oxygen species (ROS) production in tumors. However, current nanocatalysts have drawbacks such as catalytic inefficiency and high toxicity. Herein, we designed a paradigm of synergy and “division of labor” bimetallic dual active sites single-atom catalyst (SAC) combined with ROS circulation and parallel catalytic therapy for efficient tumor therapy. Both Fe and Co atoms were isolated in the N-doped carbon material with a sharp-angled dodecahedron in a monodisperse state to form an independent bimetallic non-alloy structured atom pair (FeCo-DIA/NC). FeCo-DIA/NC synergistically initiates both Fenton and Fenton-like reactions, directly and simultaneously catalyzing H2O2 and O2 into ROS, including hydroxyl radicals (•OH), superoxide ions (O2•−), and singlet oxygen (1O2). The above ROS are further converted into H2O2 in the acid tumor microenvironment (TME), forming a “ROS Cycle” for highly efficient tumor inhibition. FeCo-DIA/NC exhibits higher activity for Fenton and Fenton-like reactions than single-atom Fe dispersed on N-doped carbon material (Fe-SIA/NC) and single-atom Co dispersed on N-doped carbon material (Co-SIA/NC). The in vitro and in vivo results show that the FeCo-DIA/NC catalyst significantly induces cell apoptosis and inhibits tumor growth. Furthermore, extremely low metal concentrations and high therapeutic effects were achieved simultaneously in FeCo-DIA/NC, highlighting the promising clinical potential. This bimetallic dual-active site monodisperse catalyst provides an important example for applying SACs in the biomedical field, moreover, the highly effective and parallel catalytic “ROS Cycle” provides an opportunity to design nanocatalysts for oncology.