Vicious Cycle‐Breaking Lipid Nanoparticles Remodeling Multicellular Crosstalk to Reverse Liver Fibrosis

Zhang, Ling‐Feng; Deng, Wen‐Qi; Huang, Qing‐Wen; Zhang, Jiao‐Jiao; Wang, Yi; Zhou, Tian‐Jiao; Xing, Lei; Jiang, Hu‐Lin

doi:10.1002/adma.202311474

Advanced Materials

2024

DOI: 10.1002/adma.202311474

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Vicious Cycle‐Breaking Lipid Nanoparticles Remodeling Multicellular Crosstalk to Reverse Liver Fibrosis

Ling‐Feng Zhang,

Wen‐Qi Deng,

Qing‐Wen Huang

et al.

Abstract: During liver fibrogenesis, the reciprocal crosstalk among capillarized liver sinusoidal endothelial cells (LSECs), activated hepatic stellate cells (HSCs) and dysfunctional hepatocytes constructs a self‐amplifying vicious cycle, greatly exacerbating the disease condition and weakening therapeutic effect. Limited by the malignant cellular interactions, the previous single‐cell centric treatment approaches showed unsatisfactory efficacy and failed to meet clinical demand. Herein, a vicious cycle‐breaking strateg… Show more

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Cited by 12 publications

References 46 publications

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Spontaneous Inflammation Resolution Inspired Nanoparticles Promote Neutrophil Apoptosis and Macrophage Efferocytosis for Acute Respiratory Distress Syndrome Treatment

Wang,

Zhang,

Zhang

et al. 2024

Adv Healthcare Materials

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During acute respiratory distress syndrome (ARDS), delayed apoptosis of neutrophils and impaired efferocytosis of macrophages constitute two critical limiting steps, leading to secondary inflammatory storm and posing a significant threat to human health. However, due to the failure of previous single target‐centric treatments to effectively address these two limiting steps in controlling the inflammatory storm, no available therapies are approved for ARDS treatment. Herein, inspired by spontaneous inflammation resolution, two kinds of Apoptosis and Efferocytosis Restored Nanoparticles (AER NPs) are proposed to overcome these two limiting steps for counteracting severe inflammatory storm. For the first limiting step, neutrophil‐targeted apoptosis‐restored nanoparticles (AR NPs) accelerated the programmed apoptosis of inflammatory neutrophils. The resolution of the first limiting step facilitated the accumulation of macrophage‐targeted and efferocytosis‐restored nanoparticles (ER NPs), thereby restoring macrophage efferocytosis and alleviating the second limiting step. The results indicated that after sequential treatment with AER NPs, recruited neutrophils decreased to 13.86%, and macrophage efferocytosis increased to 563.24%. AER NPs promoted inflammation resolution and established a self‐healing virtuous loop by addressing the two limiting steps, ultimately effectively treating ARDS. This work suggests that a strategy inspired by inflammation resolution holds promise as a potential approach for advancing inflammation therapy.

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Spontaneous Inflammation Resolution Inspired Nanoparticles Promote Neutrophil Apoptosis and Macrophage Efferocytosis for Acute Respiratory Distress Syndrome Treatment

Wang,

Zhang,

Zhang

et al. 2024

Adv Healthcare Materials

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Modulating Fibrotic Mechanical Microenvironment for Idiopathic Pulmonary Fibrosis Therapy

Li,

Lin,

Han

et al. 2024

Advanced Materials

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Idiopathic pulmonary fibrosis (IPF) is exacerbated by injurious mechanical forces that destabilize the pulmonary mechanical microenvironment homeostasis, leading to alveolar dysfunction and exacerbating disease severity. However, given the inherent mechanosensitivity of fibrotic lungs, where type II alveolar epithelial cells (AEC IIs) are subjected to persistent stretching and overactivated myofibroblasts experience malignant interactions during mechanotransduction, it becomes imperative to develop effective strategies to modulate the pulmonary mechanical microenvironment. Herein, cyclo (RGDfC) peptide‐decorated zeolitic imidazolate framework‐8 nanoparticles (named ZDFPR NPs) are constructed to target and repair the aberrant mechanical force levels in pathological lungs. Specifically, reduces mechanical tension in AEC IIs by pH‐responsive ZDFPR NPs that release zinc ions and 7, 8‐dihydroxyflavone to promote alveolar repair and differentiation. Meanwhile, malignant interactions between myofibroblast contractility and extracellular matrix stiffness during mechanotransduction are disrupted by the fasudil inhibition ROCK signaling pathway. The results show that ZDFPR NPs successfully restored pulmonary mechanical homeostasis and terminated the fibrosis process in bleomycin‐induced fibrotic mice. This study not only presents a promising strategy for modulating pulmonary mechanical microenvironment but also pioneers a novel avenue for IPF treatment.

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

Zhang,

Deng,

Wang

et al. 2024

Advanced Science

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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.

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Vicious Cycle‐Breaking Lipid Nanoparticles Remodeling Multicellular Crosstalk to Reverse Liver Fibrosis

Cited by 12 publications

References 46 publications

Spontaneous Inflammation Resolution Inspired Nanoparticles Promote Neutrophil Apoptosis and Macrophage Efferocytosis for Acute Respiratory Distress Syndrome Treatment

Spontaneous Inflammation Resolution Inspired Nanoparticles Promote Neutrophil Apoptosis and Macrophage Efferocytosis for Acute Respiratory Distress Syndrome Treatment

Modulating Fibrotic Mechanical Microenvironment for Idiopathic Pulmonary Fibrosis Therapy

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

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