Pathological Microenvironment‐Remodeling Nanoparticles to Alleviate Liver Fibrosis: Reversing Hepatocytes‐Hepatic Stellate Cells Malignant Crosstalk
During the onset and malignant development of liver fibrosis, the pernicious interplay between damaged hepatocytes and activated hepatic stellate cells (HSCs) induce a self-perpetuating vicious cycle, deteriorating fibrosis progression and posing a grave threat to public health. The secretions released by damaged hepatocytes and activated HSCs interact through autocrine or paracrine mechanisms, involving multiple signaling pathways. This interaction creates a harsh microenvironment and weakens the therapeutic efficacy of single-cell-centric drugs. Herein, a malignant crosstalk-blocking strategy is prompted to remodel vicious cellular interplay and reverse pathological microenvironment to put an end to liver fibrosis. Collagenases modified, bardoxolone and siTGF-β co-delivered nanoparticles (C-NPs/BT) are designed to penetrate the deposited collagen barriers and further regulate the cellular interactions through upregulating anti-oxidative stress capacity and eliminating the pro-fibrogenic effects of TGF-β. The C-NPs/BT shows successful remodeling of vicious cellular crosstalk and significant disease regression in animal models. This study presents an innovative strategy to modulate cellular interactions for enhanced anti-fibrotic therapy and suggests a promising approach for treating other chronic liver diseases.
Authors
- Xinghuan Wang (ORCID: https://orcid.org/0000-0003-3497-0024)
- Yu‐Kyoung Oh (ORCID: https://orcid.org/0000-0002-0969-3339)
- Zhen‐Bin Ding (ORCID: https://orcid.org/0000-0001-6613-8270)
- Jaiwoo Lee (ORCID: https://orcid.org/0000-0003-1856-2688)
- Lei Xing (ORCID: https://orcid.org/0000-0003-3507-4547)
- Hu‐Lin Jiang (ORCID: https://orcid.org/0000-0002-1620-1777)
- Lingfeng Zhang (ORCID: https://orcid.org/0000-0003-4491-1554)
- Yi Wang (ORCID: https://orcid.org/0000-0001-6965-9696)
- Wen‐Qi Deng
- Qing‐Wen Huang
- Liang Qi (ORCID: https://orcid.org/0000-0002-0235-7957)
- Tian‐Jiao Zhou (ORCID: https://orcid.org/0000-0003-0222-1774)
- Su‐Qing Liang
Institutions
- Seoul National University (KR)
- China Pharmaceutical University (CN)
- Yanbian University (CN)
- New Generation University College (ET)
- Nanjing Children's Hospital (CN)
- Zhongda Hospital Southeast University (CN)
- Second Affiliated Hospital of Nanjing Medical University (CN)
- Sungkyunkwan University (KR)
Publication Details
- Journal
- Advanced Science
- Published
- 2024-10-28
- DOI
- https://doi.org/10.1002/advs.202408898
- Citations
- 10
- Primary Topic
- Liver physiology and pathology
- Type
- article
- Field-Weighted Citation Impact
- 3.69
Funders
- National Research Foundation
- National Natural Science Foundation of China
- Ministry of Education of the People's Republic of China
- China Pharmaceutical University
- China Postdoctoral Science Foundation
- Government of Jiangsu Province
- State Administration of Foreign Experts Affairs
- Natural Science Foundation of Jiangsu Province
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Ministry of Science and ICT, South Korea
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities