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A Zinc‐ and Calcium‐Rich Lysosomal Nanoreactor Rescues Monocyte/Macrophage Dysfunction under Sepsis

Sepsis is a dysregulation of the immune response to pathogens and has high morbidity and mortality worldwide. However, the unclear mapping and course of dysregulated immune cells currently hinders the development of advanced therapeutic strategies to treat sepsis. Here, evidence is provided using si...

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Autores principales: Zhao, Qin, Gong, Zijian, Wang, Jiaolong, Fu, Liangliang, Zhang, Jing, Wang, Can, Miron, Richard J., Yuan, Quan, Zhang, Yufeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9951326/
https://www.ncbi.nlm.nih.gov/pubmed/36596693
http://dx.doi.org/10.1002/advs.202205097
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author Zhao, Qin
Gong, Zijian
Wang, Jiaolong
Fu, Liangliang
Zhang, Jing
Wang, Can
Miron, Richard J.
Yuan, Quan
Zhang, Yufeng
author_facet Zhao, Qin
Gong, Zijian
Wang, Jiaolong
Fu, Liangliang
Zhang, Jing
Wang, Can
Miron, Richard J.
Yuan, Quan
Zhang, Yufeng
author_sort Zhao, Qin
collection PubMed
description Sepsis is a dysregulation of the immune response to pathogens and has high morbidity and mortality worldwide. However, the unclear mapping and course of dysregulated immune cells currently hinders the development of advanced therapeutic strategies to treat sepsis. Here, evidence is provided using single‐cell RNA sequencing from peripheral blood mononuclear cells in sepsis that pathogens attacking monocytes/macrophages disrupt their immune function. The results reveal an enormous decline in monocytes/macrophages in sepsis and chart the evolution of their impaired phagocytosis (Pha) capabilities. Inspired by these findings, nanoparticles, named “Alpha‐MOFs,” are developed that target dysfunctional monocytes/macrophages to actively (A) lift (L) Pha by the release of lysosome‐sensitive ions from a mineralized metal–organic framework (MOF). Alpha‐MOFs have good stability and biosafety in peripheral blood and efficiently targeted monocytes/macrophages. They also release calcium and zinc ions into monocyte/macrophage lysosomes to promote the Pha and degradation of bacteria. Taken together, these results suggest that Alpha‐MOFs rescue monocytes/macrophages dysfunction and effectively improve their survival rate during sepsis.
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spelling pubmed-99513262023-02-25 A Zinc‐ and Calcium‐Rich Lysosomal Nanoreactor Rescues Monocyte/Macrophage Dysfunction under Sepsis Zhao, Qin Gong, Zijian Wang, Jiaolong Fu, Liangliang Zhang, Jing Wang, Can Miron, Richard J. Yuan, Quan Zhang, Yufeng Adv Sci (Weinh) Research Articles Sepsis is a dysregulation of the immune response to pathogens and has high morbidity and mortality worldwide. However, the unclear mapping and course of dysregulated immune cells currently hinders the development of advanced therapeutic strategies to treat sepsis. Here, evidence is provided using single‐cell RNA sequencing from peripheral blood mononuclear cells in sepsis that pathogens attacking monocytes/macrophages disrupt their immune function. The results reveal an enormous decline in monocytes/macrophages in sepsis and chart the evolution of their impaired phagocytosis (Pha) capabilities. Inspired by these findings, nanoparticles, named “Alpha‐MOFs,” are developed that target dysfunctional monocytes/macrophages to actively (A) lift (L) Pha by the release of lysosome‐sensitive ions from a mineralized metal–organic framework (MOF). Alpha‐MOFs have good stability and biosafety in peripheral blood and efficiently targeted monocytes/macrophages. They also release calcium and zinc ions into monocyte/macrophage lysosomes to promote the Pha and degradation of bacteria. Taken together, these results suggest that Alpha‐MOFs rescue monocytes/macrophages dysfunction and effectively improve their survival rate during sepsis. John Wiley and Sons Inc. 2023-01-03 /pmc/articles/PMC9951326/ /pubmed/36596693 http://dx.doi.org/10.1002/advs.202205097 Text en © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Zhao, Qin
Gong, Zijian
Wang, Jiaolong
Fu, Liangliang
Zhang, Jing
Wang, Can
Miron, Richard J.
Yuan, Quan
Zhang, Yufeng
A Zinc‐ and Calcium‐Rich Lysosomal Nanoreactor Rescues Monocyte/Macrophage Dysfunction under Sepsis
title A Zinc‐ and Calcium‐Rich Lysosomal Nanoreactor Rescues Monocyte/Macrophage Dysfunction under Sepsis
title_full A Zinc‐ and Calcium‐Rich Lysosomal Nanoreactor Rescues Monocyte/Macrophage Dysfunction under Sepsis
title_fullStr A Zinc‐ and Calcium‐Rich Lysosomal Nanoreactor Rescues Monocyte/Macrophage Dysfunction under Sepsis
title_full_unstemmed A Zinc‐ and Calcium‐Rich Lysosomal Nanoreactor Rescues Monocyte/Macrophage Dysfunction under Sepsis
title_short A Zinc‐ and Calcium‐Rich Lysosomal Nanoreactor Rescues Monocyte/Macrophage Dysfunction under Sepsis
title_sort zinc‐ and calcium‐rich lysosomal nanoreactor rescues monocyte/macrophage dysfunction under sepsis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9951326/
https://www.ncbi.nlm.nih.gov/pubmed/36596693
http://dx.doi.org/10.1002/advs.202205097
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