期刊
JOURNAL OF MATERIALS CHEMISTRY B
卷 9, 期 8, 页码 1988-2000出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0tb02476g
关键词
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资金
- National Natural Science Foundation of China [81771976]
- National Key Research and Development Program of China [2018YFC1901202]
- Fundamental Research Funds for the Central Universities
- Southeast University
- Southeast University and Nanjing Medical University
This study introduces a novel nanofiber drug carrier that inhibits tumor hypoxia and promotes H2O2 accumulation, achieving chemo/chemodynamic synergistic therapy and significantly suppressing tumor growth. The method also enhances efficacy by increasing ROS accumulation and cutting off energy supply.
Chemo/chemodynamic synergistic therapy is a promising strategy to improve the antitumor effect. However, hypoxia and a limited amount of hydrogen peroxide (H2O2) 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 (O-2) consumption to promote H2O2 accumulation in the tumor. Inside tumor cells, Met can inhibit the consumption of O-2 to relieve tumor hypoxia by suppressing mitochondrial respiration. The alleviated-tumor hypoxia can not only elevate H2O2 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 Cu2+ 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.
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