Bioinspired Copper Single-Atom Catalysts for Tumor Parallel Catalytic Therapy

The oxidation of intracellular biomolecules by reactive oxygen species (ROS) forms the basis for ROS-based tumor therapy. However, the current therapeutic modalities cannot catalyze H₂ O₂ and O₂ concurrently for ROS generation, thereby leading to unsatisfactory therapeutic efficacy. Herein, it is reported a bioinspired hollow N-doped carbon sphere doped with a single-atom copper species (Cu-HNCS) that can directly catalyze the decomposition of both oxygen and hydrogen peroxide to ROS, namely superoxide ion (O₂ •^- ) and the hydroxyl radical (•OH), respectively, in an acidic tumor microenvironment for the oxidation of intracellular biomolecules without external energy input, thus resulting in an enhanced tumor growth inhibitory effect. Notably, the Fenton reaction turnover frequency of Cu species in Cu-HNCS is ≈5000 times higher than that of Fe in commercial Fe₃ O₄ nanoparticles. Experimental results and density functional theory calculations reveal that the high catalytic activity of Cu-HNCS originates from the single-atom copper, and the calculation predicts a next-generation Fenton catalyst. This work provides an effective paradigm of tumor parallel catalytic therapy for considerably enhanced therapeutic efficacy.