Copper(II)-based metal-organic framework delivery of calcium ascorbate for enhanced chemodynamic therapy via H2O2 self-supply and glutathione depletion
Chemodynamic therapy (CDT) is a promising cancer treatment strategy. However, mild acidic pH, insufficient H2O2 content, and overexpressed glutathione (GSH) in the tumor microenvironment (TME) severely impair CDT efficiency. In this study, a novel therapeutic nanosystem (Cu/ZIF-8/Vc-Ca/HA) was constructed for H2O2 self-supply and GSH depletion co-enhanced CDT. Typically, calcium ascorbate (Vc-Ca) loaded on the surface of Cu2+-doped ZIF-8 (Cu/ZIF-8) was designed as an original source for H2O2 generation, and a hyaluronic acid (HA) shell was subsequently coated to act as a tumor-targeted "guide" and protective layer. Along with the HA shell disintegrated in the TME, exposed Cu/ZIF-8/Vc-Ca dissociated in the tumor acidic microenvironment, thus triggering the release of Vc-Ca and Cu2+. Vc-Ca selectively produced H2O2 in tumor cells, which provided abundant H2O2 for boosting Fenton-like reactions. Meanwhile, the released Cu2+ could get converted into Cu+ by consuming excess intracellular GSH, which could reduce the tumor antioxidant capability of the nanosystem. Moreover, byproduct Cu+ reacted with abundant H2O2 by a highly efficient Fenton-like reaction to generate toxic ˙OH. Biological assays indicated that the Cu/ZIF-8/HAVc-Ca nanosystem showed significant anticancer activity by enhancing the CDT process. This study may provide a new strategy for improving the effectiveness of CDT.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Biomaterials science - 12(2024), 7 vom: 26. März, Seite 1871-1882 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Meng [VerfasserIn] |
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| Links: |
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| Themen: |
183E4W213W |
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| Anmerkungen: |
Date Completed 27.03.2024 Date Revised 27.03.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1039/d3bm01922e |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369015266 |
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| 245 | 1 | 0 | |a Copper(II)-based metal-organic framework delivery of calcium ascorbate for enhanced chemodynamic therapy via H2O2 self-supply and glutathione depletion |
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| 520 | |a Chemodynamic therapy (CDT) is a promising cancer treatment strategy. However, mild acidic pH, insufficient H2O2 content, and overexpressed glutathione (GSH) in the tumor microenvironment (TME) severely impair CDT efficiency. In this study, a novel therapeutic nanosystem (Cu/ZIF-8/Vc-Ca/HA) was constructed for H2O2 self-supply and GSH depletion co-enhanced CDT. Typically, calcium ascorbate (Vc-Ca) loaded on the surface of Cu2+-doped ZIF-8 (Cu/ZIF-8) was designed as an original source for H2O2 generation, and a hyaluronic acid (HA) shell was subsequently coated to act as a tumor-targeted "guide" and protective layer. Along with the HA shell disintegrated in the TME, exposed Cu/ZIF-8/Vc-Ca dissociated in the tumor acidic microenvironment, thus triggering the release of Vc-Ca and Cu2+. Vc-Ca selectively produced H2O2 in tumor cells, which provided abundant H2O2 for boosting Fenton-like reactions. Meanwhile, the released Cu2+ could get converted into Cu+ by consuming excess intracellular GSH, which could reduce the tumor antioxidant capability of the nanosystem. Moreover, byproduct Cu+ reacted with abundant H2O2 by a highly efficient Fenton-like reaction to generate toxic ˙OH. Biological assays indicated that the Cu/ZIF-8/HAVc-Ca nanosystem showed significant anticancer activity by enhancing the CDT process. This study may provide a new strategy for improving the effectiveness of CDT | ||
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| 700 | 1 | |a Xue, Hongjin |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Jiaxin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Xue, Mei |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Jianfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Zhihong |e verfasserin |4 aut | |
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