Cargando…

Peritoneal M2 macrophage-derived extracellular vesicles as natural multitarget nanotherapeutics to attenuate cytokine storms after severe infections

Cytokine storms are a primary cause of multiple organ damage and death after severe infections, such as SARS-CoV-2. However, current single cytokine-targeted strategies display limited therapeutic efficacy. Here, we report that peritoneal M2 macrophage-derived extracellular vesicles (M2-EVs) are mul...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Yizhuo, Liu, Shuyun, Li, Lan, Li, Ling, Zhou, Xueli, Wan, Meihua, Lou, Peng, Zhao, Meng, Lv, Ke, Yuan, Yujia, Chen, Younan, Lu, Yanrong, Cheng, Jingqiu, Liu, Jingping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257240/
https://www.ncbi.nlm.nih.gov/pubmed/35792186
http://dx.doi.org/10.1016/j.jconrel.2022.06.063
_version_ 1784741300944240640
author Wang, Yizhuo
Liu, Shuyun
Li, Lan
Li, Ling
Zhou, Xueli
Wan, Meihua
Lou, Peng
Zhao, Meng
Lv, Ke
Yuan, Yujia
Chen, Younan
Lu, Yanrong
Cheng, Jingqiu
Liu, Jingping
author_facet Wang, Yizhuo
Liu, Shuyun
Li, Lan
Li, Ling
Zhou, Xueli
Wan, Meihua
Lou, Peng
Zhao, Meng
Lv, Ke
Yuan, Yujia
Chen, Younan
Lu, Yanrong
Cheng, Jingqiu
Liu, Jingping
author_sort Wang, Yizhuo
collection PubMed
description Cytokine storms are a primary cause of multiple organ damage and death after severe infections, such as SARS-CoV-2. However, current single cytokine-targeted strategies display limited therapeutic efficacy. Here, we report that peritoneal M2 macrophage-derived extracellular vesicles (M2-EVs) are multitarget nanotherapeutics that can be used to resolve cytokine storms. In detail, primary peritoneal M2 macrophages exhibited superior anti-inflammatory potential than immobilized cell lines. Systemically administered M2-EVs entered major organs and were taken up by phagocytes (e.g., macrophages). M2-EV treatment effectively reduced excessive cytokine (e.g., TNF-α and IL-6) release in vitro and in vivo, thereby attenuating oxidative stress and multiple organ (lung, liver, spleen and kidney) damage in endotoxin-induced cytokine storms. Moreover, M2-EVs simultaneously inhibited multiple key proinflammatory pathways (e.g., NF-κB, JAK-STAT and p38 MAPK) by regulating complex miRNA-gene and gene-gene networks, and this effect was collectively mediated by many functional cargos (miRNAs and proteins) in EVs. In addition to the direct anti-inflammatory role, human peritoneal M2-EVs expressed angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2 spike protein, and thus could serve as nanodecoys to prevent SARS-CoV-2 pseudovirus infection in vitro. As cell-derived nanomaterials, the therapeutic index of M2-EVs can be further improved by genetic/chemical modification or loading with specific drugs. This study highlights that peritoneal M2-EVs are promising multifunctional nanotherapeutics to attenuate infectious disease-related cytokine storms.
format Online
Article
Text
id pubmed-9257240
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Elsevier B.V.
record_format MEDLINE/PubMed
spelling pubmed-92572402022-07-06 Peritoneal M2 macrophage-derived extracellular vesicles as natural multitarget nanotherapeutics to attenuate cytokine storms after severe infections Wang, Yizhuo Liu, Shuyun Li, Lan Li, Ling Zhou, Xueli Wan, Meihua Lou, Peng Zhao, Meng Lv, Ke Yuan, Yujia Chen, Younan Lu, Yanrong Cheng, Jingqiu Liu, Jingping J Control Release Article Cytokine storms are a primary cause of multiple organ damage and death after severe infections, such as SARS-CoV-2. However, current single cytokine-targeted strategies display limited therapeutic efficacy. Here, we report that peritoneal M2 macrophage-derived extracellular vesicles (M2-EVs) are multitarget nanotherapeutics that can be used to resolve cytokine storms. In detail, primary peritoneal M2 macrophages exhibited superior anti-inflammatory potential than immobilized cell lines. Systemically administered M2-EVs entered major organs and were taken up by phagocytes (e.g., macrophages). M2-EV treatment effectively reduced excessive cytokine (e.g., TNF-α and IL-6) release in vitro and in vivo, thereby attenuating oxidative stress and multiple organ (lung, liver, spleen and kidney) damage in endotoxin-induced cytokine storms. Moreover, M2-EVs simultaneously inhibited multiple key proinflammatory pathways (e.g., NF-κB, JAK-STAT and p38 MAPK) by regulating complex miRNA-gene and gene-gene networks, and this effect was collectively mediated by many functional cargos (miRNAs and proteins) in EVs. In addition to the direct anti-inflammatory role, human peritoneal M2-EVs expressed angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2 spike protein, and thus could serve as nanodecoys to prevent SARS-CoV-2 pseudovirus infection in vitro. As cell-derived nanomaterials, the therapeutic index of M2-EVs can be further improved by genetic/chemical modification or loading with specific drugs. This study highlights that peritoneal M2-EVs are promising multifunctional nanotherapeutics to attenuate infectious disease-related cytokine storms. Elsevier B.V. 2022-09 2022-07-06 /pmc/articles/PMC9257240/ /pubmed/35792186 http://dx.doi.org/10.1016/j.jconrel.2022.06.063 Text en © 2022 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Wang, Yizhuo
Liu, Shuyun
Li, Lan
Li, Ling
Zhou, Xueli
Wan, Meihua
Lou, Peng
Zhao, Meng
Lv, Ke
Yuan, Yujia
Chen, Younan
Lu, Yanrong
Cheng, Jingqiu
Liu, Jingping
Peritoneal M2 macrophage-derived extracellular vesicles as natural multitarget nanotherapeutics to attenuate cytokine storms after severe infections
title Peritoneal M2 macrophage-derived extracellular vesicles as natural multitarget nanotherapeutics to attenuate cytokine storms after severe infections
title_full Peritoneal M2 macrophage-derived extracellular vesicles as natural multitarget nanotherapeutics to attenuate cytokine storms after severe infections
title_fullStr Peritoneal M2 macrophage-derived extracellular vesicles as natural multitarget nanotherapeutics to attenuate cytokine storms after severe infections
title_full_unstemmed Peritoneal M2 macrophage-derived extracellular vesicles as natural multitarget nanotherapeutics to attenuate cytokine storms after severe infections
title_short Peritoneal M2 macrophage-derived extracellular vesicles as natural multitarget nanotherapeutics to attenuate cytokine storms after severe infections
title_sort peritoneal m2 macrophage-derived extracellular vesicles as natural multitarget nanotherapeutics to attenuate cytokine storms after severe infections
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257240/
https://www.ncbi.nlm.nih.gov/pubmed/35792186
http://dx.doi.org/10.1016/j.jconrel.2022.06.063
work_keys_str_mv AT wangyizhuo peritonealm2macrophagederivedextracellularvesiclesasnaturalmultitargetnanotherapeuticstoattenuatecytokinestormsaftersevereinfections
AT liushuyun peritonealm2macrophagederivedextracellularvesiclesasnaturalmultitargetnanotherapeuticstoattenuatecytokinestormsaftersevereinfections
AT lilan peritonealm2macrophagederivedextracellularvesiclesasnaturalmultitargetnanotherapeuticstoattenuatecytokinestormsaftersevereinfections
AT liling peritonealm2macrophagederivedextracellularvesiclesasnaturalmultitargetnanotherapeuticstoattenuatecytokinestormsaftersevereinfections
AT zhouxueli peritonealm2macrophagederivedextracellularvesiclesasnaturalmultitargetnanotherapeuticstoattenuatecytokinestormsaftersevereinfections
AT wanmeihua peritonealm2macrophagederivedextracellularvesiclesasnaturalmultitargetnanotherapeuticstoattenuatecytokinestormsaftersevereinfections
AT loupeng peritonealm2macrophagederivedextracellularvesiclesasnaturalmultitargetnanotherapeuticstoattenuatecytokinestormsaftersevereinfections
AT zhaomeng peritonealm2macrophagederivedextracellularvesiclesasnaturalmultitargetnanotherapeuticstoattenuatecytokinestormsaftersevereinfections
AT lvke peritonealm2macrophagederivedextracellularvesiclesasnaturalmultitargetnanotherapeuticstoattenuatecytokinestormsaftersevereinfections
AT yuanyujia peritonealm2macrophagederivedextracellularvesiclesasnaturalmultitargetnanotherapeuticstoattenuatecytokinestormsaftersevereinfections
AT chenyounan peritonealm2macrophagederivedextracellularvesiclesasnaturalmultitargetnanotherapeuticstoattenuatecytokinestormsaftersevereinfections
AT luyanrong peritonealm2macrophagederivedextracellularvesiclesasnaturalmultitargetnanotherapeuticstoattenuatecytokinestormsaftersevereinfections
AT chengjingqiu peritonealm2macrophagederivedextracellularvesiclesasnaturalmultitargetnanotherapeuticstoattenuatecytokinestormsaftersevereinfections
AT liujingping peritonealm2macrophagederivedextracellularvesiclesasnaturalmultitargetnanotherapeuticstoattenuatecytokinestormsaftersevereinfections