Academic Journal
Hyaluronic acid-coated metal-organic framework for co-delivery of Sirtuin 3 gene and zinc to inhibit liver fibrosis.
| Τίτλος: | Hyaluronic acid-coated metal-organic framework for co-delivery of Sirtuin 3 gene and zinc to inhibit liver fibrosis. |
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| Συγγραφείς: | Jung J; Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 14662, Republic of Korea; Department of Biomedical-Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 14662, Republic of Korea., Jin M; Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 14662, Republic of Korea; Department of Biomedical-Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 14662, Republic of Korea., Park N; Department of Nanomedical Engineering, Korea National University of Transportation, 50 Daehak-ro, Chungju-si, Chungcheongbuk-do 27469, Republic of Korea., Choi H; Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 14662, Republic of Korea; Department of Biomedical-Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 14662, Republic of Korea., Na K; Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 14662, Republic of Korea; Department of Biomedical-Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 14662, Republic of Korea. Electronic address: kna6997@catholic.ac.kr. |
| Πηγή: | Acta biomaterialia [Acta Biomater] 2026 Aug; Vol. 219, pp. 510-525. Date of Electronic Publication: 2026 Jun 17. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: England NLM ID: 101233144 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-7568 (Electronic) Linking ISSN: 17427061 NLM ISO Abbreviation: Acta Biomater Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Kidlington, Oxford, UK : Elsevier, c2004- |
| Ιατρικοί όροι (MeSH): | Hyaluronic Acid*/chemistry , Hyaluronic Acid*/pharmacology , Zinc*/pharmacology , Zinc*/chemistry , Liver Cirrhosis*/pathology , Liver Cirrhosis*/therapy , Liver Cirrhosis*/genetics , Liver Cirrhosis*/metabolism , Sirtuin 3*/genetics , Gene Transfer Techniques*, Hepatic Stellate Cells/metabolism ; Hepatic Stellate Cells/pathology ; Imidazoles/chemistry ; Imidazoles/pharmacology ; Macrophages/metabolism ; Macrophages/pathology ; Endothelial Cells/metabolism ; Animals ; Mice ; Male ; Gene Therapy Agents ; Mice, Inbred C57BL ; Plasmids ; Metal-Organic Frameworks |
| Περίληψη: | Liver fibrosis is characterized by excessive accumulation of extracellular matrix and disruption of hepatic sinusoidal architecture. However, effective therapies targeting microvascular dysfunction and immune imbalance remain limited. In this study, we present hyaluronic acid (HA)-coated zeolitic imidazolate framework-8 (ZIF-8) formulations (HDZs) loaded with sirtuin 3 (SIRT3) plasmid DNA, designed for the co-delivery of SIRT3 and bioavailable zinc ions to restore hepatic homeostasis. The HA coating promoted cellular uptake across multiple hepatic cell types, including hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs), and macrophages. In vitro, the nanoplatform suppressed stellate cell activation, maintained LSEC fenestrae, and induced macrophage polarization toward an anti-inflammatory phenotype. The pH-responsive disassembly of ZIF-8 enabled efficient intracellular release of SIRT3 plasmid DNA, while the simultaneous release of zinc ions contributed to cytoprotective effects. In fibrotic mouse models, the treatment significantly reduced collagen deposition, preserved sinusoidal structure, and promoted M2-dominant macrophage polarization, accompanied by improved liver function and elevated hepatic zinc levels. These results demonstrate a combined anti-fibrotic effect achieved through coordinated genetic modulation and micronutrient support. Collectively, this HDZ platform represents a multifunctional non-viral gene delivery strategy for liver fibrosis and offers potential for treating other chronic liver diseases involving mitochondrial dysfunction, immune dysregulation, and microvascular injury. STATEMENT OF SIGNIFICANCE: Liver fibrosis lacks effective treatments that simultaneously address structural damage, immune imbalance, and mitochondrial dysfunction. This study introduces a hyaluronic acid-coated ZIF-8 nanoplatform that co-delivers a mitochondrial regulatory gene and bioavailable zinc, enabling coordinated genetic and micronutrient modulation within the fibrotic liver. Unlike conventional approaches that target a single pathway or cell type, this platform engages hepatic stellate cells, liver sinusoidal endothelial cells, and macrophages, leading to reduced fibrosis, preserved sinusoidal architecture, and immune reprogramming in vivo. By integrating non-viral gene delivery with controlled zinc release, this work provides a multifunctional strategy for restoring hepatic homeostasis and expands the therapeutic potential of metal-organic framework-based nanomedicine for chronic liver diseases. (Copyright © 2026 Acta Materialia Inc. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Gene delivery; Liver fibrosis; SIRT3; ZIF-8; Zinc ion |
| Substance Nomenclature: | 9004-61-9 (Hyaluronic Acid) J41CSQ7QDS (Zinc) EC 3.5.1.- (Sirtuin 3) 0 (ZIF-8 metal-organic framework) 0 (Imidazoles) 0 (Metal-Organic Frameworks) |
| Entry Date(s): | Date Created: 20260617 Date Completed: 20260720 Latest Revision: 20260720 |
| Update Code: | 20260721 |
| DOI: | 10.1016/j.actbio.2026.06.032 |
| PMID: | 42309181 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1878-7568 |
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| DOI: | 10.1016/j.actbio.2026.06.032 |