One-Pot Synthesis-Biocompatible Copper–Tripeptide Complex as a Nanocatalytic Medicine to Enhance Chemodynamic Therapy

Abstract

Chemodynamic therapy (CDT) is a kind of method utilizing hydroxyl radicals (^•OH) generated by Fenton or Fenton-like reactions <i>in situ</i> 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) <i>in vitro</i>, 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.