Biodegradable copper–metformin nanoscale coordination polymers for enhanced chemo/chemodynamic synergistic therapy by reducing oxygen consumption to promote H2O2 accumulation. Issue 8 (29th January 2021)

• Record Type: Journal Article
• Authors: Meng, Xiangyu; Zhang, Xuezhong; Lei, Yunfeng; Cao, Dongwei; Wang, Zhifei
• Is Part Of: Journal of materials chemistry. Volume 9:Issue 8(2021)
• Page Start: 1988
• Page End: 2000
• Publication Date: 2021-01-29
• Subjects: Materials -- Periodicals; Chemistry, Analytic -- Periodicals; Biomedical materials -- Research -- Periodicals; 543.0284
• DOI: 10.1039/d0tb02476g
• Languages: English
• ISSNs: 2050-750X

Abstract

Abstract : A new therapeutic nanoplatform based on Dox@Cu–Met NPs was constructed, which could reduce the consumption of O2 and elevate H2 O2 content for effective chemo/chemodynamic synergistic therapy. Abstract : Chemo/chemodynamic synergistic therapy is a promising strategy to improve the antitumor effect. However, hypoxia and a limited amount of hydrogen peroxide (H2 O2 ) in the tumor microenvironment (TME) severely restrict the therapeutic efficacy of this combined treatment. Herein, we report biodegradable doxorubicin (Dox)-loaded copper–metformin (Met) nanoscale coordination polymers (Dox@Cu–Met NPs), which exert a chemo/chemodynamic synergistic therapeutic effect by reducing oxygen (O2 ) consumption to promote H2 O2 accumulation in the tumor. Inside tumor cells, Met can inhibit the consumption of O2 to relieve tumor hypoxia by suppressing mitochondrial respiration. The alleviated-tumor hypoxia can not only elevate H2 O2 content via the Dox-activated cascade reaction of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) and superoxide dismutase (SOD), but also improve the efficacy of Dox. More importantly, the depletion of glutathione (GSH) accompanies the whole treatment process, which can realize the conversion of Cu 2+ to Cu + and boost reactive oxygen species (ROS) accumulation to improve chemodynamic therapy (CDT) efficacy. Meanwhile, Met is expected to cut off the energy supply by inhibiting respiration, leading to starvation therapy. In vivo investigations demonstrate that tumor growth is significantly inhibited through the enhanced chemo/chemodynamic synergistic treatment. This work provides a new paradigm for cancer therapy using an economical and straightforward method to construct a synergistic nanomedicine platform.