Chemodynamic therapy (CDT) is a kind of method utilizing hydroxyl radicals (•OH) generated by Fenton or Fenton-like reactions in situ to kill tumor cells. Copper, a cofactor of many intracellular enzymes, which has good biocompatibility, is a transition metal with extremely high efficiency in the Fenton-like reaction. However, when the intracellular free copper exceeds the threshold, it will bring serious side effects. Hence, we used the chelation between glutathione (GSH) and copper ions to produce a nanocatalytic drug, which was named as Cu–GSSG NPs, to fix free copper. With the aid of hydrogen peroxide (H2O2) in vitro, Cu–GSSG NPs catalyzed it to •OH radicals, which could be confirmed by the electron spin resonance spectrum and the degradation experiment of methylene blue. Based on these results, we further studied the intracellular properties of Cu–GSSG NPs and found that Cu–GSSG NPs could react with the overexpressed H2O2 in tumor cells to produce •OH radicals effectively by the Fenton-like reaction to induce cell death. Therefore, Cu–GSSG NPs could be a kind of potential “green” nanocatalytic drug with good biocompatibility to achieve CDT.

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