Pathological Microenvironment‐Remodeling Nanoparticles to Alleviate Liver Fibrosis: Reversing Hepatocytes‐Hepatic Stellate Cells Malignant Crosstalk
Abstract 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 secreti...
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2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202408898 |
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| author | Ling‐Feng Zhang Wen‐Qi Deng Xing‐Huan Wang Qing‐Wen Huang Su‐Qing Liang Ze‐Quan Ding Liang Qi Yi Wang Tian‐Jiao Zhou Lei Xing Jai‐Woo Lee Yu‐Kyoung Oh Hu‐Lin Jiang |
| author_facet | Ling‐Feng Zhang Wen‐Qi Deng Xing‐Huan Wang Qing‐Wen Huang Su‐Qing Liang Ze‐Quan Ding Liang Qi Yi Wang Tian‐Jiao Zhou Lei Xing Jai‐Woo Lee Yu‐Kyoung Oh Hu‐Lin Jiang |
| author_sort | Ling‐Feng Zhang |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-d447aa45aef3437196cf2ffc950e0d45 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-d447aa45aef3437196cf2ffc950e0d452025-01-29T09:50:18ZengWileyAdvanced Science2198-38442025-01-01124n/an/a10.1002/advs.202408898Pathological Microenvironment‐Remodeling Nanoparticles to Alleviate Liver Fibrosis: Reversing Hepatocytes‐Hepatic Stellate Cells Malignant CrosstalkLing‐Feng Zhang0Wen‐Qi Deng1Xing‐Huan Wang2Qing‐Wen Huang3Su‐Qing Liang4Ze‐Quan Ding5Liang Qi6Yi Wang7Tian‐Jiao Zhou8Lei Xing9Jai‐Woo Lee10Yu‐Kyoung Oh11Hu‐Lin Jiang12State Key Laboratory of Natural Medicines Department of Pharmaceutics China Pharmaceutical University Nanjing 210009 ChinaState Key Laboratory of Natural Medicines Department of Pharmaceutics China Pharmaceutical University Nanjing 210009 ChinaState Key Laboratory of Natural Medicines Department of Pharmaceutics China Pharmaceutical University Nanjing 210009 ChinaState Key Laboratory of Natural Medicines Department of Pharmaceutics China Pharmaceutical University Nanjing 210009 ChinaState Key Laboratory of Natural Medicines Department of Pharmaceutics China Pharmaceutical University Nanjing 210009 ChinaDepartment of Pediatric Surgery Children's Hospital of Nanjing Medical University 72 Guangzhou Road Nanjing Jiangsu 210000 ChinaDepartment of Endocrinology Zhongda Hospital School of Medicine Southeast University Nanjing 210009 ChinaState Key Laboratory of Natural Medicines Department of Pharmaceutics China Pharmaceutical University Nanjing 210009 ChinaState Key Laboratory of Natural Medicines Department of Pharmaceutics China Pharmaceutical University Nanjing 210009 ChinaState Key Laboratory of Natural Medicines Department of Pharmaceutics China Pharmaceutical University Nanjing 210009 ChinaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National University Seoul 08826 South KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National University Seoul 08826 South KoreaState Key Laboratory of Natural Medicines Department of Pharmaceutics China Pharmaceutical University Nanjing 210009 ChinaAbstract 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.https://doi.org/10.1002/advs.202408898cellular crosstalkchemogene therapyhepatic stellate cellhepatocyteliver fibrosis |
| spellingShingle | Ling‐Feng Zhang Wen‐Qi Deng Xing‐Huan Wang Qing‐Wen Huang Su‐Qing Liang Ze‐Quan Ding Liang Qi Yi Wang Tian‐Jiao Zhou Lei Xing Jai‐Woo Lee Yu‐Kyoung Oh Hu‐Lin Jiang Pathological Microenvironment‐Remodeling Nanoparticles to Alleviate Liver Fibrosis: Reversing Hepatocytes‐Hepatic Stellate Cells Malignant Crosstalk Advanced Science cellular crosstalk chemogene therapy hepatic stellate cell hepatocyte liver fibrosis |
| title | Pathological Microenvironment‐Remodeling Nanoparticles to Alleviate Liver Fibrosis: Reversing Hepatocytes‐Hepatic Stellate Cells Malignant Crosstalk |
| title_full | Pathological Microenvironment‐Remodeling Nanoparticles to Alleviate Liver Fibrosis: Reversing Hepatocytes‐Hepatic Stellate Cells Malignant Crosstalk |
| title_fullStr | Pathological Microenvironment‐Remodeling Nanoparticles to Alleviate Liver Fibrosis: Reversing Hepatocytes‐Hepatic Stellate Cells Malignant Crosstalk |
| title_full_unstemmed | Pathological Microenvironment‐Remodeling Nanoparticles to Alleviate Liver Fibrosis: Reversing Hepatocytes‐Hepatic Stellate Cells Malignant Crosstalk |
| title_short | Pathological Microenvironment‐Remodeling Nanoparticles to Alleviate Liver Fibrosis: Reversing Hepatocytes‐Hepatic Stellate Cells Malignant Crosstalk |
| title_sort | pathological microenvironment remodeling nanoparticles to alleviate liver fibrosis reversing hepatocytes hepatic stellate cells malignant crosstalk |
| topic | cellular crosstalk chemogene therapy hepatic stellate cell hepatocyte liver fibrosis |
| url | https://doi.org/10.1002/advs.202408898 |
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