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Carbon Nitride-Based siRNA Vectors with Self-Produced O 2 Effects for Targeting Combination Therapy of Liver Fibrosis via HIF-1α-Mediated TGF-β1/Smad Pathway.
- Source :
-
Advanced healthcare materials [Adv Healthc Mater] 2023 Nov; Vol. 12 (29), pp. e2301485. Date of Electronic Publication: 2023 Jul 27. - Publication Year :
- 2023
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Abstract
- Hypoxia is an important feature, which can upregulate the hypoxia-inducible factor-1α (HIF-1α) expression and promote the activation of hepatic stellate cells (HSCs), leading to liver fibrosis. Currently, effective treatment for liver fibrosis is extremely lacking. Herein, a safe and effective method is established to downregulate the expression of HIF-1α in HSCs via targeted delivery of VA-PEG-modified CNs-based nanosheets-encapsulated (VA-PEG-CN@GQDs) HIF-1α small interfering RNA (HIF-1α-siRNA). Due to the presence of lipase in the liver, the reversible release of siRNA can be promoted to complete the transfection process. Simultaneously, VA-PEG-CN@GQD nanosheets enable trigger the water splitting process to produce O <subscript>2</subscript> under near-infrared (NIR) irradiation, thereby improving the hypoxic environment of the liver fibrosis site and maximizing the downregulation of HIF-1α expression to improve the therapeutic effect, as demonstrated in liver fibrosis mice. Such combination therapy can inhibit the activation of HSCs via HIF-1α-mediated TGF-β1/Smad pathway, achieving outstanding therapeutic effects in liver fibrosis mice. In conclusion, this study proposes a novel strategy for the treatment of liver fibrosis by regulating the hypoxic environment and the expression of HIF-1α at lesion site.<br /> (© 2023 Wiley-VCH GmbH.)
Details
- Language :
- English
- ISSN :
- 2192-2659
- Volume :
- 12
- Issue :
- 29
- Database :
- MEDLINE
- Journal :
- Advanced healthcare materials
- Publication Type :
- Academic Journal
- Accession number :
- 37463681
- Full Text :
- https://doi.org/10.1002/adhm.202301485