Targeted inhibition of autophagy in hepatic stellate cells by hydroxychloroquine : An effective therapeutic approach for the treatment of liver fibrosis
© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd..
BACKGROUND AND PURPOSE: Liver fibrosis is a wound-healing reaction which is the main cause of chronic liver diseases worldwide. The activated hepatic stellate cell (aHSC) is the main driving factor in the development of liver fibrosis. Inhibiting autophagy of aHSC can prevent the progression of liver fibrosis, but inhibiting autophagy of other liver cells has opposite effects. Hence, targeted inhibition of autophagy in aHSC is quite necessary for the treatment of liver fibrosis, which prompts us to explore the targeted delivery system of small molecule autophagy inhibitor hydroxychloroquine (HCQ) that can target aHSC and alleviate the liver fibrosis.
METHODS: The delivery system of HCQretinol-liposome nanoparticles (HCQ@ROL-LNPs) targeting aHSC was constructed by the film dispersion and pH-gradient method. TGF-β-induced HSC activation and thioacetamide (TAA)-induced liver fibrosis mice model were established, and the targeting ability and therapeutic effect of HCQ@ROL-LNPs in liver fibrosis were studied subsequently in vitro and in vivo.
RESULTS: HCQROL-LNPs have good homogeneity and stability. They inhibited the autophagy of aHSC selectively by HCQ and reduced the deposition of extracellular matrix (ECM) and the damage to other liver cells. Compared with the free HCQ and HCQ@LNPs, HCQ@ROL-LNPs had good targeting ability, showing enhanced therapeutic effect and low toxicity to other organs.
CONCLUSION: Construction of HCQROL-LNPs delivery system lays a theoretical and experimental foundation for the treatment of liver fibrosis and promotes the development of clinical therapeutic drugs for liver diseases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Liver international : official journal of the International Association for the Study of the Liver - (2024) vom: 12. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hou, Li-Shuang [VerfasserIn] |
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| Links: |
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| Themen: |
Autophagy inhibition |
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| Anmerkungen: |
Date Revised 12.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1111/liv.15915 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370959906 |
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| 100 | 1 | |a Hou, Li-Shuang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Targeted inhibition of autophagy in hepatic stellate cells by hydroxychloroquine |b An effective therapeutic approach for the treatment of liver fibrosis |
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| 500 | |a Date Revised 12.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. | ||
| 520 | |a BACKGROUND AND PURPOSE: Liver fibrosis is a wound-healing reaction which is the main cause of chronic liver diseases worldwide. The activated hepatic stellate cell (aHSC) is the main driving factor in the development of liver fibrosis. Inhibiting autophagy of aHSC can prevent the progression of liver fibrosis, but inhibiting autophagy of other liver cells has opposite effects. Hence, targeted inhibition of autophagy in aHSC is quite necessary for the treatment of liver fibrosis, which prompts us to explore the targeted delivery system of small molecule autophagy inhibitor hydroxychloroquine (HCQ) that can target aHSC and alleviate the liver fibrosis | ||
| 520 | |a METHODS: The delivery system of HCQretinol-liposome nanoparticles (HCQ@ROL-LNPs) targeting aHSC was constructed by the film dispersion and pH-gradient method. TGF-β-induced HSC activation and thioacetamide (TAA)-induced liver fibrosis mice model were established, and the targeting ability and therapeutic effect of HCQ@ROL-LNPs in liver fibrosis were studied subsequently in vitro and in vivo | ||
| 520 | |a RESULTS: HCQROL-LNPs have good homogeneity and stability. They inhibited the autophagy of aHSC selectively by HCQ and reduced the deposition of extracellular matrix (ECM) and the damage to other liver cells. Compared with the free HCQ and HCQ@LNPs, HCQ@ROL-LNPs had good targeting ability, showing enhanced therapeutic effect and low toxicity to other organs | ||
| 520 | |a CONCLUSION: Construction of HCQROL-LNPs delivery system lays a theoretical and experimental foundation for the treatment of liver fibrosis and promotes the development of clinical therapeutic drugs for liver diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a autophagy inhibition | |
| 650 | 4 | |a hepatic stellate cell | |
| 650 | 4 | |a hydroxychloroquine | |
| 650 | 4 | |a liver fibrosis | |
| 650 | 4 | |a targeted therapy | |
| 700 | 1 | |a Zhai, Xiao-Pei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yao-Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Xing, Jie-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Si-Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Xiao-Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Bang-Le |e verfasserin |4 aut | |
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