A ferroptosis-reinforced nanocatalyst enhances chemodynamic therapy through dual H2O2 production and oxidative stress amplification
Copyright © 2024 Elsevier B.V. All rights reserved..
The existence of a delicate redox balance in tumors usually leads to cancer treatment failure. Breaking redox homeostasis by amplifying oxidative stress and reducing glutathione (GSH) can accelerate cancer cell death. Herein, we construct a ferroptosis-reinforced nanocatalyst (denoted as HBGL) to amplify intracellular oxidative stress via dual H2O2 production-assisted chemodynamic therapy (CDT). Specifically, a long-circulating liposome is employed to deliver hemin (a natural iron-containing substrate for Fenton reaction and ferroptosis), β-lapachone (a DNA topoisomerase inhibitor with H2O2 generation capacity for chemotherapy), and glucose oxidase (which can consume glucose for starvation therapy and generate H2O2). HBGL can achieve rapid, continuous, and massive H2O2 and •OH production and GSH depletion in cancer cells, resulting in increased intracellular oxidative stress. Additionally, hemin can reinforce the ferroptosis-inducing ability of HBGL, which is reflected in the downregulation of glutathione peroxidase-4 and the accumulation of lipid peroxide. Notably, HBGL can disrupt endo/lysosomes and impair mitochondrial function in cancer cells. HBGL exhibits effective tumor-killing ability without eliciting obvious side effects, indicating its clinical translation potential for synergistic starvation therapy, chemotherapy, ferroptosis therapy, and CDT. Overall, this nanocatalytic liposome may be a promising candidate for achieving potentiated cancer treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:367 |
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| Enthalten in: |
Journal of controlled release : official journal of the Controlled Release Society - 367(2024) vom: 01. März, Seite 892-904 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhu, Xiao-Yu [VerfasserIn] |
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| Links: |
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| Themen: |
β-lapachone |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 25.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jconrel.2024.01.049 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367687836 |
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| 520 | |a The existence of a delicate redox balance in tumors usually leads to cancer treatment failure. Breaking redox homeostasis by amplifying oxidative stress and reducing glutathione (GSH) can accelerate cancer cell death. Herein, we construct a ferroptosis-reinforced nanocatalyst (denoted as HBGL) to amplify intracellular oxidative stress via dual H2O2 production-assisted chemodynamic therapy (CDT). Specifically, a long-circulating liposome is employed to deliver hemin (a natural iron-containing substrate for Fenton reaction and ferroptosis), β-lapachone (a DNA topoisomerase inhibitor with H2O2 generation capacity for chemotherapy), and glucose oxidase (which can consume glucose for starvation therapy and generate H2O2). HBGL can achieve rapid, continuous, and massive H2O2 and •OH production and GSH depletion in cancer cells, resulting in increased intracellular oxidative stress. Additionally, hemin can reinforce the ferroptosis-inducing ability of HBGL, which is reflected in the downregulation of glutathione peroxidase-4 and the accumulation of lipid peroxide. Notably, HBGL can disrupt endo/lysosomes and impair mitochondrial function in cancer cells. HBGL exhibits effective tumor-killing ability without eliciting obvious side effects, indicating its clinical translation potential for synergistic starvation therapy, chemotherapy, ferroptosis therapy, and CDT. Overall, this nanocatalytic liposome may be a promising candidate for achieving potentiated cancer treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chemodynamic therapy | |
| 650 | 4 | |a Ferroptosis | |
| 650 | 4 | |a Hemin | |
| 650 | 4 | |a Redox homeostasis | |
| 650 | 4 | |a β-lapachone | |
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| 700 | 1 | |a Wang, Tian-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Hao-Ran |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Shun-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Cheng-Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yan-Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xinping |e verfasserin |4 aut | |
| 700 | 1 | |a Shan, Bai-Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Fu-Gen |e verfasserin |4 aut | |
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