A Facile Au Dot-Based Nanodrug for Enhanced Redox Dyshomeostasis in Chemodynamic Therapy

Insufficient hydrogen peroxide (H₂O₂) in tumor microenvironment severely limits the therapeutic effect of chemodynamic therapy (CDT), while excessive glutathione (GSH) scavenges the generated hydroxyl radical (•OH) to reduce oxidative stress, making the CDT consequence even poorer. Herein, a facile yet vigorous therapeutic nanodrug, which integrates polyethylene glycol (PEG)-functionalized gold nanodots (Au NPs) with ferrocene (Fc), is fabricated for enhanced CDT by redox dyshomeostasis with both GSH depletion and boosted oxidative stress. The constructed Au NPs-PEG-Fc (APF) nanodrug depletes GSH by competitive binding, catalyzes glucose to generate H₂O₂ with its glucose oxidase-mimicking activity, and further catalyzes H₂O₂ to generate •OH through the Fc-based Fenton reaction. Finally, it enhances redox dyshomeostasis through both the depletion of GSH and generation of •OH. Both in vitro and in vivo results show that the APF nanodrug can elevate oxidative stress to enhance the efficacy of CDT. Overall, this study provides a promising strategy for disrupting the redox balance to enhance the efficacy of CDT.