Pathological Microenvironment‐Remodeling Nanoparticles to Alleviate Liver Fibrosis: Reversing Hepatocytes‐Hepatic Stellate Cells Malignant Crosstalk

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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Main Authors: 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
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Advanced Science
Subjects:
cellular crosstalk
chemogene therapy
hepatic stellate cell
hepatocyte
liver fibrosis
Online Access:https://doi.org/10.1002/advs.202408898
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Summary: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.
ISSN:2198-3844

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