Engineered extracellular vesicles derived from primary M2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury

Abstract Background Uncontrollable inflammation and nerve cell apoptosis are the most destructive pathological response after spinal cord injury (SCI). So, inflammation suppression combined with neuroprotection is one of the most promising strategies to treat SCI. Engineered extracellular vesicles w...

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Autores principales:	Chuanjie Zhang, Daoyong Li, Hengshuo Hu, Zhe Wang, Jinyu An, Zhanshan Gao, Kaihua Zhang, Xifan Mei, Chao Wu, He Tian
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Spinal cord injury Extracellular vesicles Curcumin M2 repolarization Neuroprotection Biotechnology TP248.13-248.65 Medical technology R855-855.5
Acceso en línea:	https://doaj.org/article/d82e3318425d4eb482fc0f9bf9af8925
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spelling	oai:doaj.org-article:d82e3318425d4eb482fc0f9bf9af89252021-11-21T12:29:32ZEngineered extracellular vesicles derived from primary M2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury10.1186/s12951-021-01123-91477-3155https://doaj.org/article/d82e3318425d4eb482fc0f9bf9af89252021-11-01T00:00:00Zhttps://doi.org/10.1186/s12951-021-01123-9https://doaj.org/toc/1477-3155Abstract Background Uncontrollable inflammation and nerve cell apoptosis are the most destructive pathological response after spinal cord injury (SCI). So, inflammation suppression combined with neuroprotection is one of the most promising strategies to treat SCI. Engineered extracellular vesicles with anti-inflammatory and neuroprotective properties are promising candidates for implementing these strategies for the treatment of SCI. Results By combining nerve growth factor (NGF) and curcumin (Cur), we prepared stable engineered extracellular vesicles of approximately 120 nm from primary M2 macrophages with anti-inflammatory and neuroprotective properties (Cur@EVs−cl−NGF). Notably, NGF was coupled with EVs by matrix metalloproteinase 9 (MMP9)-a cleavable linker to release at the injured site accurately. Through targeted experiments, we found that these extracellular vesicles could actively and effectively accumulate at the injured site of SCI mice, which greatly improved the bioavailability of the drugs. Subsequently, Cur@EVs−cl−NGF reached the injured site and could effectively inhibit the uncontrollable inflammatory response to protect the spinal cord from secondary damage; in addition, Cur@EVs−cl−NGF could release NGF into the microenvironment in time to exert a neuroprotective effect against nerve cell damage. Conclusions A series of in vivo and in vitro experiments showed that the engineered extracellular vesicles significantly improved the microenvironment after injury and promoted the recovery of motor function after SCI. We provide a new method for inflammation suppression combined with neuroprotective strategies to treat SCI. Graphical AbstractChuanjie ZhangDaoyong LiHengshuo HuZhe WangJinyu AnZhanshan GaoKaihua ZhangXifan MeiChao WuHe TianBMCarticleSpinal cord injuryExtracellular vesiclesCurcuminM2 repolarizationNeuroprotectionBiotechnologyTP248.13-248.65Medical technologyR855-855.5ENJournal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Spinal cord injury Extracellular vesicles Curcumin M2 repolarization Neuroprotection Biotechnology TP248.13-248.65 Medical technology R855-855.5
spellingShingle	Spinal cord injury Extracellular vesicles Curcumin M2 repolarization Neuroprotection Biotechnology TP248.13-248.65 Medical technology R855-855.5 Chuanjie Zhang Daoyong Li Hengshuo Hu Zhe Wang Jinyu An Zhanshan Gao Kaihua Zhang Xifan Mei Chao Wu He Tian Engineered extracellular vesicles derived from primary M2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury
description	Abstract Background Uncontrollable inflammation and nerve cell apoptosis are the most destructive pathological response after spinal cord injury (SCI). So, inflammation suppression combined with neuroprotection is one of the most promising strategies to treat SCI. Engineered extracellular vesicles with anti-inflammatory and neuroprotective properties are promising candidates for implementing these strategies for the treatment of SCI. Results By combining nerve growth factor (NGF) and curcumin (Cur), we prepared stable engineered extracellular vesicles of approximately 120 nm from primary M2 macrophages with anti-inflammatory and neuroprotective properties (Cur@EVs−cl−NGF). Notably, NGF was coupled with EVs by matrix metalloproteinase 9 (MMP9)-a cleavable linker to release at the injured site accurately. Through targeted experiments, we found that these extracellular vesicles could actively and effectively accumulate at the injured site of SCI mice, which greatly improved the bioavailability of the drugs. Subsequently, Cur@EVs−cl−NGF reached the injured site and could effectively inhibit the uncontrollable inflammatory response to protect the spinal cord from secondary damage; in addition, Cur@EVs−cl−NGF could release NGF into the microenvironment in time to exert a neuroprotective effect against nerve cell damage. Conclusions A series of in vivo and in vitro experiments showed that the engineered extracellular vesicles significantly improved the microenvironment after injury and promoted the recovery of motor function after SCI. We provide a new method for inflammation suppression combined with neuroprotective strategies to treat SCI. Graphical Abstract
format	article
author	Chuanjie Zhang Daoyong Li Hengshuo Hu Zhe Wang Jinyu An Zhanshan Gao Kaihua Zhang Xifan Mei Chao Wu He Tian
author_facet	Chuanjie Zhang Daoyong Li Hengshuo Hu Zhe Wang Jinyu An Zhanshan Gao Kaihua Zhang Xifan Mei Chao Wu He Tian
author_sort	Chuanjie Zhang
title	Engineered extracellular vesicles derived from primary M2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury
title_short	Engineered extracellular vesicles derived from primary M2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury
title_full	Engineered extracellular vesicles derived from primary M2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury
title_fullStr	Engineered extracellular vesicles derived from primary M2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury
title_full_unstemmed	Engineered extracellular vesicles derived from primary M2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury
title_sort	engineered extracellular vesicles derived from primary m2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury
publisher	BMC
publishDate	2021
url	https://doaj.org/article/d82e3318425d4eb482fc0f9bf9af8925
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Engineered extracellular vesicles derived from primary M2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury

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