A Facile Au Dot‐Based Nanodrug for Enhanced Redox Dyshomeostasis in Chemodynamic Therapy. Issue 3 (9th December 2022) - Wang, Huafeng
Abstract: Insufficient hydrogen peroxide (H2 O2 ) 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 H2 O2 with its glucose oxidase‐mimicking activity, and further catalyzes H2 O2 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. Abstract : The road to simplicity: A facile yet vigorous Au dot‐based nanodrug is engineered. It integrates polyethylene glycol functionalized gold nanoparticles with ferrocene, enabling in situ glutathione depletion and generation of hydroxyl radicals through competitive binding, enzyme‐like catalysis, and Fenton reaction, thus boosting redox dyshomeostasis and markedly improving therapeutic efficiency of chemodynamic therapy.