期刊
ACS NANO
卷 15, 期 5, 页码 8039-8068出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.1c00498
关键词
glutathione; glutathione-depleting agents; redox modulation; reactive oxygen species; drug resistance; tumor microenvironment; nanodrug; multimodal therapy
类别
资金
- National Natural Science Foundation of China [21673037]
- Open Project of Guangxi Key Laboratory of High-Incidence-Tumor Prevention & Treatment and Key Laboratory of High-Incidence-Tumor Prevention & Treatment, Ministry of Education [GKEKF202001]
Overexpression of glutathione in cancer cells leads to resistance to anticancer therapies, making GSH depletion a potential target for cancer treatments. By combining with mainstream cancer therapies, GSH-depleting agents can enhance cancer cells responses to cell death stimuli.
Cancer cells frequently exhibit resistance to various molecular and nanoscale drugs, which inevitably affects the drugs' therapeutic outcomes. Overexpression of glutathione (GSH) has been observed in many cancer cells, and solid evidence has corroborated the resulting tumor resistance to a variety of anticancer therapies, suggesting that this biochemical characteristic of cancer cells can be developed as a potential target for cancer treatments. The single treatment of GSH-depleting agents can potentiate the responses of the cancer cells to different cell death stimuli; therefore, as an adjunctive strategy, GSH depletion is usually combined with mainstream cancer therapies for enhancing the therapeutic outcomes. Propelled by the rapid development of nanotechnology, GSH-depleting agents can be readily constructed into anticancer nanomedicines, which have shown a steep rise over the past decade. Here, we review the common GSH-depleting nanomedicines which have been widely applied in synergistic cancer treatments in recent years. Some current challenges and future perspectives for GSH depletion-based cancer therapies are also presented. With the understanding of the structure-property relationship and action mechanisms of these biomaterials, we hope that the GSH-depleting nanotechnology will be further developed to realize more effective disease treatments and even achieve successful clinical translations.
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