Fe/Cu–AuNP nanocomposites as enzyme-like catalysts to modulate the tumor microenvironment for enhanced synergistic cancer therapy

Abstract

The intensive investigation of chemodynamic therapy (CDT) for tumor eradication revealed that the therapeutic effects of this ROS-mediated therapy are limited by endogenous reductants and inefficient Fenton-like reactions. In this study, we developed a new Fe/Cu–AuNP–PEG nanocomposite to enhance CDT and provide a synergistic treatment for tumors. The Fe/Cu–AuNP–PEG nanocomposite demonstrated effective ˙OH production and high photothermal conversion efficiency under 808 nm illumination, which promoted the ˙OH production, thereby enhancing the CDT efficacy and exhibiting a synergistic treatment for cancer. More importantly, the Fe/Cu–AuNP–PEG nanocomposite showed the ability to deplete GSH and catalyze glucose to generate H₂O₂, which facilitated the Fenton-like reaction and reduced the antioxidant properties of tumors, further improving the efficacy of CDT. Therefore, the Fe/Cu–AuNP–PEG nanocomposite, with horseradish peroxidase-like, glutathione peroxidase-like, and glucose oxidase-like activities, is a promising anti-tumor agent for integrating enhanced CDT and photothermal therapy (PTT) with the enhancement of synergistic therapeutic effects.