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

Abstract

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.

Yeast‐Controlled Double‐Shelled CaCO3/CaF2 Hollow Nanospheres with Hierarchically Porous for Sustained pH‐Sensitive Drug Release

“…Before application, the biocompatibility of drug carrier was evaluated, which was a crucial factor for drug delivery. [ 38‐39 ] We analyzed the biocompatibility of HPCaCO 3 /CaF 2 using the MTT assay. As shown in Figures 3a and 3b, the cytotoxicity test of HPCaCO 3 /CaF 2 revealed no significant effect on whether normal cells or cancer cells, even at a high concentration.…”

A Paramagnetic Metal‐Organic Framework Enhances Mild Magnetic Hyperthermia Therapy by Downregulating Heat Shock Proteins and Promoting Ferroptosis via Aggravation of Two‐Way Regulated Redox Dyshomeostasis

“…GSH consumption of Lac‐FcMOF was assessed using a reduced GSH content assay kit while Fenton catalytic activity of Lac‐FcMOF was assessed using methylene blue (MB) to detect ∙OH. [ 55 , 56 ] The concentration of GSH decreased with increasing concentration of Lac‐FcMOF and incubation time (Figure 2f ), which can be ascribed to ferricenium ions consuming GSH through redox reactions. [ 31 , 57 ] MB degradation by Lac‐FcMOF was not observed at pH 7.4 (Figure S13a , Supporting Information), but was observed in the tumor cell microenvironment mimic (10 mM H 2 O 2 , pH 5.0), as the production of ∙OH through Lac‐FcMOF‐catalyzed Fenton reaction requires a lower pH (Figure 2g ).…”