Biomimetic MOF Nanocarrier‐Mediated Synergistic Delivery of Mitochondria and Anti‐Inflammatory miRNA to Alleviate Acute Lung Injury

Abstract Acute lung injury (ALI) is a clinically critical disease characterized by overwhelming inflammatory response and significant tissue damage with no specific treatment available currently. As a key player in the pathogenesis of ALI, macrophages are aberrantly activated and polarize toward the...

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Main Authors: Xin Shou, Changjiang Chen, Hangjie Ying, Zhiyun Liu, Lingyao Zeng, Qiujie Li, Lanjie Lei, Bingyong Mao, Wei Zhang, Shumao Cui, Liyun Shi
Format: Article
Language:English
Published: Wiley 2025-04-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202416594
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author Xin Shou
Changjiang Chen
Hangjie Ying
Zhiyun Liu
Lingyao Zeng
Qiujie Li
Lanjie Lei
Bingyong Mao
Wei Zhang
Shumao Cui
Liyun Shi
author_facet Xin Shou
Changjiang Chen
Hangjie Ying
Zhiyun Liu
Lingyao Zeng
Qiujie Li
Lanjie Lei
Bingyong Mao
Wei Zhang
Shumao Cui
Liyun Shi
author_sort Xin Shou
collection DOAJ
description Abstract Acute lung injury (ALI) is a clinically critical disease characterized by overwhelming inflammatory response and significant tissue damage with no specific treatment available currently. As a key player in the pathogenesis of ALI, macrophages are aberrantly activated and polarize toward the pro‐inflammatory phenotypes, leading to overzealous inflammation and lung injury. Mitochondria is recognized as a crucial signaling hub governing macrophage function and polarization, deregulation of which is causatively related with defective metabolism of macrophages, deregulated inflammation, and hence ALI. Herein, an inflammation‐responsive, biomimetic metal‐organic framework (MOF) nanoplatform, termed a127/mito@ZIF@Ma is developed, which is sophistically designed for synergistic delivery of macrophage‐derived mitochondria and anti‐inflammatory miRNA‐127 antagonist to resume pulmonary macrophages homeostasis and alleviate lung inflammation and injury. Notably, macrophage membrane encapsulation conferred the biomimetic MOF with enhanced transport efficacy both in vitro and in vivo. Therefore, the administration of the nanoparticles accordingly conferred a profound protection of mice against lung inflammation and injury induced by either bacterial or viral infection with unnoticeable tissue toxicity. The study thus devises a novel MOF‐based nanosystem that integrates mitochondria transplantation and miRNA therapeutics, which may open a new avenue for treating ALI and relevant critical diseases.
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spelling doaj-art-0975695bf41f4bc8b2aae1fb4ee7f28d2025-08-20T02:24:50ZengWileyAdvanced Science2198-38442025-04-011216n/an/a10.1002/advs.202416594Biomimetic MOF Nanocarrier‐Mediated Synergistic Delivery of Mitochondria and Anti‐Inflammatory miRNA to Alleviate Acute Lung InjuryXin Shou0Changjiang Chen1Hangjie Ying2Zhiyun Liu3Lingyao Zeng4Qiujie Li5Lanjie Lei6Bingyong Mao7Wei Zhang8Shumao Cui9Liyun Shi10Key lab of Artificial Organs and Computational Medicine Institute of Translational Medicine Zhejiang Shuren University Hangzhou Zhejiang 310015 ChinaDepartment of Immunology Nanjing University of Chinese Medicine Nanjing Jiangsu 210023 ChinaDepartment of Experiment Center Zhejiang Cancer Hospital Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences Hangzhou Zhejiang 310022 ChinaKey lab of Artificial Organs and Computational Medicine Institute of Translational Medicine Zhejiang Shuren University Hangzhou Zhejiang 310015 ChinaKey lab of Artificial Organs and Computational Medicine Institute of Translational Medicine Zhejiang Shuren University Hangzhou Zhejiang 310015 ChinaKey lab of Artificial Organs and Computational Medicine Institute of Translational Medicine Zhejiang Shuren University Hangzhou Zhejiang 310015 ChinaKey lab of Artificial Organs and Computational Medicine Institute of Translational Medicine Zhejiang Shuren University Hangzhou Zhejiang 310015 ChinaState Key Laboratory of Food Science and Resources Jiangnan University Wuxi Jiangsu 214122 ChinaDepartment of Immunology Nanjing University of Chinese Medicine Nanjing Jiangsu 210023 ChinaState Key Laboratory of Food Science and Resources Jiangnan University Wuxi Jiangsu 214122 ChinaKey lab of Artificial Organs and Computational Medicine Institute of Translational Medicine Zhejiang Shuren University Hangzhou Zhejiang 310015 ChinaAbstract Acute lung injury (ALI) is a clinically critical disease characterized by overwhelming inflammatory response and significant tissue damage with no specific treatment available currently. As a key player in the pathogenesis of ALI, macrophages are aberrantly activated and polarize toward the pro‐inflammatory phenotypes, leading to overzealous inflammation and lung injury. Mitochondria is recognized as a crucial signaling hub governing macrophage function and polarization, deregulation of which is causatively related with defective metabolism of macrophages, deregulated inflammation, and hence ALI. Herein, an inflammation‐responsive, biomimetic metal‐organic framework (MOF) nanoplatform, termed a127/mito@ZIF@Ma is developed, which is sophistically designed for synergistic delivery of macrophage‐derived mitochondria and anti‐inflammatory miRNA‐127 antagonist to resume pulmonary macrophages homeostasis and alleviate lung inflammation and injury. Notably, macrophage membrane encapsulation conferred the biomimetic MOF with enhanced transport efficacy both in vitro and in vivo. Therefore, the administration of the nanoparticles accordingly conferred a profound protection of mice against lung inflammation and injury induced by either bacterial or viral infection with unnoticeable tissue toxicity. The study thus devises a novel MOF‐based nanosystem that integrates mitochondria transplantation and miRNA therapeutics, which may open a new avenue for treating ALI and relevant critical diseases.https://doi.org/10.1002/advs.202416594acute lung injuryinflammationmacrophagemiRNAMOF nanocarrier
spellingShingle Xin Shou
Changjiang Chen
Hangjie Ying
Zhiyun Liu
Lingyao Zeng
Qiujie Li
Lanjie Lei
Bingyong Mao
Wei Zhang
Shumao Cui
Liyun Shi
Biomimetic MOF Nanocarrier‐Mediated Synergistic Delivery of Mitochondria and Anti‐Inflammatory miRNA to Alleviate Acute Lung Injury
Advanced Science
acute lung injury
inflammation
macrophage
miRNA
MOF nanocarrier
title Biomimetic MOF Nanocarrier‐Mediated Synergistic Delivery of Mitochondria and Anti‐Inflammatory miRNA to Alleviate Acute Lung Injury
title_full Biomimetic MOF Nanocarrier‐Mediated Synergistic Delivery of Mitochondria and Anti‐Inflammatory miRNA to Alleviate Acute Lung Injury
title_fullStr Biomimetic MOF Nanocarrier‐Mediated Synergistic Delivery of Mitochondria and Anti‐Inflammatory miRNA to Alleviate Acute Lung Injury
title_full_unstemmed Biomimetic MOF Nanocarrier‐Mediated Synergistic Delivery of Mitochondria and Anti‐Inflammatory miRNA to Alleviate Acute Lung Injury
title_short Biomimetic MOF Nanocarrier‐Mediated Synergistic Delivery of Mitochondria and Anti‐Inflammatory miRNA to Alleviate Acute Lung Injury
title_sort biomimetic mof nanocarrier mediated synergistic delivery of mitochondria and anti inflammatory mirna to alleviate acute lung injury
topic acute lung injury
inflammation
macrophage
miRNA
MOF nanocarrier
url https://doi.org/10.1002/advs.202416594
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