Decoy exosomes as a novel biologic reagent to antagonize inflammation

Natalie Duong,1 Kevin Curley,1 Annie Brown,1 Alexander Campanelli,1 Mai Anh Do,1 Daniel Levy,1 Adarsh Tantry,1 Gerard Marriott,2 Biao Lu11Department of Bioengineering, School of Engineering, Santa Clara University, Santa Clara, CA 95053, USA; 2Department of Bioengineering and Tsinghua-Berkeley Shenz...

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Autores principales: Duong N, Curley K, Brown A, Campanelli A, Do MA, Levy D, Tantry A, Marriott G, Lu B
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2019
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Acceso en línea:https://doaj.org/article/d6ba57ce27e948ec9ff1af81e06ed84d
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spelling oai:doaj.org-article:d6ba57ce27e948ec9ff1af81e06ed84d2021-12-02T04:44:59ZDecoy exosomes as a novel biologic reagent to antagonize inflammation1178-2013https://doaj.org/article/d6ba57ce27e948ec9ff1af81e06ed84d2019-05-01T00:00:00Zhttps://www.dovepress.com/decoy-exosomes-as-a-novel-biologic-reagent-to-antagonize-inflammation-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Natalie Duong,1 Kevin Curley,1 Annie Brown,1 Alexander Campanelli,1 Mai Anh Do,1 Daniel Levy,1 Adarsh Tantry,1 Gerard Marriott,2 Biao Lu11Department of Bioengineering, School of Engineering, Santa Clara University, Santa Clara, CA 95053, USA; 2Department of Bioengineering and Tsinghua-Berkeley Shenzhen Institute, University of California at Berkeley, Berkeley, CA 94720, USABackground: Exosomes are ubiquitous naturally secreted stable nanovesicles that can be engineered to target and deliver novel therapeutics to treat a host of human diseases.Methods: We engineered the surfaces of cell-derived nanovesicles to act as decoys in the treatment of inflammation by antagonizing the major proinflammatory cytokine, tumor necrosis factor alpha (TNFα).Results: Decoy exosomes were generated by displaying the TNFα binding domain of human TNF receptor-1 (hTNFR1) on the outer surface of exosomes using stably transfected HEK293 cells. We developed an efficient method to purify the engineered exosomes from conditioned medium based on sequential centrifugation, ultrafiltration, and precipitation. We characterized decoy exosomes using immune-quantification, nanoparticle tracking analysis, and confocal microscopy to confirm that they retain the correct orientation, size, and shape of naturally produced exosomes. We demonstrated the engineered decoy exosomes specifically antagonize activities of TNFα using an inflammatory reporter cell line.Conclusions: Decoy exosomes produced in human cells serve as a novel biologic reagent for antagonizing inflammatory signaling mediated by TNFα.Keywords: Decoy exosomes, Inflammation, CD63, Receptor, TNFα, Drug delivery  Duong NCurley KBrown ACampanelli ADo MALevy DTantry AMarriott GLu BDove Medical PressarticleExosomedecoy exosomeTNFαinflammationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 3413-3425 (2019)
institution DOAJ
collection DOAJ
language EN
topic Exosome
decoy exosome
TNFα
inflammation
Medicine (General)
R5-920
spellingShingle Exosome
decoy exosome
TNFα
inflammation
Medicine (General)
R5-920
Duong N
Curley K
Brown A
Campanelli A
Do MA
Levy D
Tantry A
Marriott G
Lu B
Decoy exosomes as a novel biologic reagent to antagonize inflammation
description Natalie Duong,1 Kevin Curley,1 Annie Brown,1 Alexander Campanelli,1 Mai Anh Do,1 Daniel Levy,1 Adarsh Tantry,1 Gerard Marriott,2 Biao Lu11Department of Bioengineering, School of Engineering, Santa Clara University, Santa Clara, CA 95053, USA; 2Department of Bioengineering and Tsinghua-Berkeley Shenzhen Institute, University of California at Berkeley, Berkeley, CA 94720, USABackground: Exosomes are ubiquitous naturally secreted stable nanovesicles that can be engineered to target and deliver novel therapeutics to treat a host of human diseases.Methods: We engineered the surfaces of cell-derived nanovesicles to act as decoys in the treatment of inflammation by antagonizing the major proinflammatory cytokine, tumor necrosis factor alpha (TNFα).Results: Decoy exosomes were generated by displaying the TNFα binding domain of human TNF receptor-1 (hTNFR1) on the outer surface of exosomes using stably transfected HEK293 cells. We developed an efficient method to purify the engineered exosomes from conditioned medium based on sequential centrifugation, ultrafiltration, and precipitation. We characterized decoy exosomes using immune-quantification, nanoparticle tracking analysis, and confocal microscopy to confirm that they retain the correct orientation, size, and shape of naturally produced exosomes. We demonstrated the engineered decoy exosomes specifically antagonize activities of TNFα using an inflammatory reporter cell line.Conclusions: Decoy exosomes produced in human cells serve as a novel biologic reagent for antagonizing inflammatory signaling mediated by TNFα.Keywords: Decoy exosomes, Inflammation, CD63, Receptor, TNFα, Drug delivery  
format article
author Duong N
Curley K
Brown A
Campanelli A
Do MA
Levy D
Tantry A
Marriott G
Lu B
author_facet Duong N
Curley K
Brown A
Campanelli A
Do MA
Levy D
Tantry A
Marriott G
Lu B
author_sort Duong N
title Decoy exosomes as a novel biologic reagent to antagonize inflammation
title_short Decoy exosomes as a novel biologic reagent to antagonize inflammation
title_full Decoy exosomes as a novel biologic reagent to antagonize inflammation
title_fullStr Decoy exosomes as a novel biologic reagent to antagonize inflammation
title_full_unstemmed Decoy exosomes as a novel biologic reagent to antagonize inflammation
title_sort decoy exosomes as a novel biologic reagent to antagonize inflammation
publisher Dove Medical Press
publishDate 2019
url https://doaj.org/article/d6ba57ce27e948ec9ff1af81e06ed84d
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