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Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates
Dexamethasone (DEX) is the first drug to show life-saving efficacy in patients with severe coronavirus disease 2019 (COVID-19), while DEX is associated with serious adverse effects. Here, we report an inhaled, Self-immunoregulatory, Extracellular Nanovesicle-based Delivery (iSEND) system by engineer...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266725/ https://www.ncbi.nlm.nih.gov/pubmed/37315135 http://dx.doi.org/10.1126/sciadv.adg3277 |
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author | Meng, Qian-Fang Tai, Wanbo Tian, Mingyao Zhuang, Xinyu Pan, Yuanwei Lai, Jialin Xu, Yangtao Xu, Zhiqiang Li, Min Zhao, Guangyu Yu, Guang-Tao Yu, Guocan Chen, Rongchang Jin, Ningyi Li, Xiao Cheng, Gong Chen, Xiaoyuan Rao, Lang |
author_facet | Meng, Qian-Fang Tai, Wanbo Tian, Mingyao Zhuang, Xinyu Pan, Yuanwei Lai, Jialin Xu, Yangtao Xu, Zhiqiang Li, Min Zhao, Guangyu Yu, Guang-Tao Yu, Guocan Chen, Rongchang Jin, Ningyi Li, Xiao Cheng, Gong Chen, Xiaoyuan Rao, Lang |
author_sort | Meng, Qian-Fang |
collection | PubMed |
description | Dexamethasone (DEX) is the first drug to show life-saving efficacy in patients with severe coronavirus disease 2019 (COVID-19), while DEX is associated with serious adverse effects. Here, we report an inhaled, Self-immunoregulatory, Extracellular Nanovesicle-based Delivery (iSEND) system by engineering neutrophil nanovesicles with cholesterols to deliver DEX for enhanced treatment of COVID-19. Relying on surface chemokine and cytokine receptors, the iSEND showed improved targeting to macrophages and neutralized broad-spectrum cytokines. The nanoDEX, made by encapsulating DEX with the iSEND, efficiently promoted the anti-inflammation effect of DEX in an acute pneumonia mouse model and suppressed DEX-induced bone density reduction in an osteoporosis rat model. Relative to an intravenous administration of DEX at 0.1 milligram per kilogram, a 10-fold lower dose of nanoDEX administered by inhalation produced even better effects against lung inflammation and injury in severe acute respiratory syndrome coronavirus 2–challenged nonhuman primates. Our work presents a safe and robust inhalation delivery platform for COVID-19 and other respiratory diseases. |
format | Online Article Text |
id | pubmed-10266725 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-102667252023-06-15 Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates Meng, Qian-Fang Tai, Wanbo Tian, Mingyao Zhuang, Xinyu Pan, Yuanwei Lai, Jialin Xu, Yangtao Xu, Zhiqiang Li, Min Zhao, Guangyu Yu, Guang-Tao Yu, Guocan Chen, Rongchang Jin, Ningyi Li, Xiao Cheng, Gong Chen, Xiaoyuan Rao, Lang Sci Adv Biomedicine and Life Sciences Dexamethasone (DEX) is the first drug to show life-saving efficacy in patients with severe coronavirus disease 2019 (COVID-19), while DEX is associated with serious adverse effects. Here, we report an inhaled, Self-immunoregulatory, Extracellular Nanovesicle-based Delivery (iSEND) system by engineering neutrophil nanovesicles with cholesterols to deliver DEX for enhanced treatment of COVID-19. Relying on surface chemokine and cytokine receptors, the iSEND showed improved targeting to macrophages and neutralized broad-spectrum cytokines. The nanoDEX, made by encapsulating DEX with the iSEND, efficiently promoted the anti-inflammation effect of DEX in an acute pneumonia mouse model and suppressed DEX-induced bone density reduction in an osteoporosis rat model. Relative to an intravenous administration of DEX at 0.1 milligram per kilogram, a 10-fold lower dose of nanoDEX administered by inhalation produced even better effects against lung inflammation and injury in severe acute respiratory syndrome coronavirus 2–challenged nonhuman primates. Our work presents a safe and robust inhalation delivery platform for COVID-19 and other respiratory diseases. American Association for the Advancement of Science 2023-06-14 /pmc/articles/PMC10266725/ /pubmed/37315135 http://dx.doi.org/10.1126/sciadv.adg3277 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Meng, Qian-Fang Tai, Wanbo Tian, Mingyao Zhuang, Xinyu Pan, Yuanwei Lai, Jialin Xu, Yangtao Xu, Zhiqiang Li, Min Zhao, Guangyu Yu, Guang-Tao Yu, Guocan Chen, Rongchang Jin, Ningyi Li, Xiao Cheng, Gong Chen, Xiaoyuan Rao, Lang Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates |
title | Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates |
title_full | Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates |
title_fullStr | Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates |
title_full_unstemmed | Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates |
title_short | Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates |
title_sort | inhalation delivery of dexamethasone with isend nanoparticles attenuates the covid-19 cytokine storm in mice and nonhuman primates |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266725/ https://www.ncbi.nlm.nih.gov/pubmed/37315135 http://dx.doi.org/10.1126/sciadv.adg3277 |
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