Fe3+-binding transferrin nanovesicles encapsulating sorafenib induce ferroptosis in hepatocellular carcinoma
© 2023. The Author(s)..
BACKGROUND: Ferroptosis, iron-dependent cell death, is an established mechanism for cancer suppression, particularly in hepatocellular carcinoma (HCC). Sorafenib (SOR), a frontline drug for the treatment of HCC, induces ferroptosis by inhibiting the Solute Carrier family 7 member 11 (SLC7A11), with inadequate ferroptosis notably contributing to SOR resistance in tumor cells.
METHODS: To further verify the biological targets associated with ferroptosis in HCC, an analysis of the Cancer Genome Atlas (TCGA) database was performed to find a significant co-upregulation of SLC7A11 and transferrin receptor (TFRC), Herein, cell membrane-derived transferrin nanovesicles (TF NVs) coupled with Fe3+ and encapsulated SOR (SORTF-Fe3+ NVs) were established to synergistically promote ferroptosis, which promoted the iron transport metabolism by TFRC/TF-Fe3+ and enhanced SOR efficacy by inhibiting the SLC7A11.
RESULTS: In vivo and in vitro experiments revealed that SORTF-Fe3+ NVs predominantly accumulate in the liver, and specifically targeted HCC cells overexpressing TFRC. Various tests demonstrated SOR@TF-Fe3+ NVs accelerated Fe3+ absorption and transformation in HCC cells. Importantly, SOR@TF-Fe3+ NVs were more effective in promoting the accumulation of lipid peroxides (LPO), inhibiting tumor proliferation, and prolonging survival rates in HCC mouse model than SOR and TF- Fe3+ NVs alone.
CONCLUSIONS: The present work provides a promising therapeutic strategy for the targeted treatment of HCC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
Biomaterials research - 27(2023), 1 vom: 01. Juli, Seite 63 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xiao, Youmei [VerfasserIn] |
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| Links: |
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| Themen: |
Biomembrane-based nanovesicles |
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| Anmerkungen: |
Date Revised 04.07.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1186/s40824-023-00401-x |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM35893091X |
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| 100 | 1 | |a Xiao, Youmei |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Fe3+-binding transferrin nanovesicles encapsulating sorafenib induce ferroptosis in hepatocellular carcinoma |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 04.07.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a BACKGROUND: Ferroptosis, iron-dependent cell death, is an established mechanism for cancer suppression, particularly in hepatocellular carcinoma (HCC). Sorafenib (SOR), a frontline drug for the treatment of HCC, induces ferroptosis by inhibiting the Solute Carrier family 7 member 11 (SLC7A11), with inadequate ferroptosis notably contributing to SOR resistance in tumor cells | ||
| 520 | |a METHODS: To further verify the biological targets associated with ferroptosis in HCC, an analysis of the Cancer Genome Atlas (TCGA) database was performed to find a significant co-upregulation of SLC7A11 and transferrin receptor (TFRC), Herein, cell membrane-derived transferrin nanovesicles (TF NVs) coupled with Fe3+ and encapsulated SOR (SORTF-Fe3+ NVs) were established to synergistically promote ferroptosis, which promoted the iron transport metabolism by TFRC/TF-Fe3+ and enhanced SOR efficacy by inhibiting the SLC7A11 | ||
| 520 | |a RESULTS: In vivo and in vitro experiments revealed that SORTF-Fe3+ NVs predominantly accumulate in the liver, and specifically targeted HCC cells overexpressing TFRC. Various tests demonstrated SOR@TF-Fe3+ NVs accelerated Fe3+ absorption and transformation in HCC cells. Importantly, SOR@TF-Fe3+ NVs were more effective in promoting the accumulation of lipid peroxides (LPO), inhibiting tumor proliferation, and prolonging survival rates in HCC mouse model than SOR and TF- Fe3+ NVs alone | ||
| 520 | |a CONCLUSIONS: The present work provides a promising therapeutic strategy for the targeted treatment of HCC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Biomembrane-based nanovesicles | |
| 650 | 4 | |a Combination therapy | |
| 650 | 4 | |a Ferroptosis | |
| 650 | 4 | |a Hepatocellular carcinoma | |
| 650 | 4 | |a Sorafenib | |
| 650 | 4 | |a Transferrin | |
| 700 | 1 | |a Xu, Zhanxue |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Rufan |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Tsai, Hsiang-I |e verfasserin |4 aut | |
| 700 | 1 | |a Zha, Hualian |e verfasserin |4 aut | |
| 700 | 1 | |a Xi, Lifang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Xiaoli |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Yanfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Changhua |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Hongbo |e verfasserin |4 aut | |
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