PEGylated PLGA Nanoparticle Delivery of Eggmanone for T Cell Modulation: Applications in Rheumatic Autoimmunity

Christopher P Haycook,1 Joseph A Balsamo,2,3 Evan B Glass,1 Charles H Williams,4 Charles C Hong,5 Amy S Major,3,6 Todd D Giorgio1 1Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA; 2Department of Pharmacology, Vanderbilt University School of Medicine, Nashville,...

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Autores principales:	Haycook CP, Balsamo JA, Glass EB, Williams CH, Hong CC, Major AS, Giorgio TD
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	advanced delivery systems. eggmanone. autoimmunity. controlled release. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/6fcaf2fe36f44573a38100c04d2567fd
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spelling	oai:doaj.org-article:6fcaf2fe36f44573a38100c04d2567fd2021-12-02T11:59:08ZPEGylated PLGA Nanoparticle Delivery of Eggmanone for T Cell Modulation: Applications in Rheumatic Autoimmunity1178-2013https://doaj.org/article/6fcaf2fe36f44573a38100c04d2567fd2020-02-01T00:00:00Zhttps://www.dovepress.com/pegylated-plga-nanoparticle-delivery-of-eggmanone-for-t-cell-modulatio-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Christopher P Haycook,1 Joseph A Balsamo,2,3 Evan B Glass,1 Charles H Williams,4 Charles C Hong,5 Amy S Major,3,6 Todd D Giorgio1 1Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA; 2Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA; 3Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt Medical Center, Nashville, TN 37232, USA; 4Department of Medicine, Division of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; 5Department of Medicine, Division of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; 6U.S., Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, USACorrespondence: Todd D GiorgioDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USAEmail todd.d.giorgio@vanderbilt.eduBackground: Helper T cell activity is dysregulated in a number of diseases including those associated with rheumatic autoimmunity. Treatment options are limited and usually consist of systemic immune suppression, resulting in undesirable consequences from compromised immunity. Hedgehog (Hh) signaling has been implicated in the activation of T cells and the formation of the immune synapse, but remains understudied in the context of autoimmunity. Modulation of Hh signaling has the potential to enable controlled immunosuppression but a potential therapy has not yet been developed to leverage this opportunity.Methods: In this work, we developed biodegradable nanoparticles to enable targeted delivery of eggmanone (Egm), a specific Hh inhibitor, to CD4+ T cell subsets. We utilized two FDA-approved polymers, poly(lactic-co-glycolic acid) and polyethylene glycol, to generate hydrolytically degradable nanoparticles. Furthermore, we employed maleimide-thiol mediated conjugation chemistry to decorate nanoparticles with anti-CD4 F(ab’) antibody fragments to enable targeted delivery of Egm.Results: Our novel delivery system achieved a highly specific association with the majority of CD4+ T cells present among a complex cell population. Additionally, we have demonstrated antigen-specific inhibition of CD4+ T cell responses mediated by nanoparticle-formulated Egm.Conclusion: This work is the first characterization of Egm’s immunomodulatory potential. Importantly, this study also suggests the potential benefit of a biodegradable delivery vehicle that is rationally designed for preferential interaction with a specific immune cell subtype for targeted modulation of Hh signaling.Keywords: advanced delivery systems, eggmanone, autoimmunity, controlled releaseHaycook CPBalsamo JAGlass EBWilliams CHHong CCMajor ASGiorgio TDDove Medical Pressarticleadvanced delivery systems. eggmanone. autoimmunity. controlled release.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 1215-1228 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	advanced delivery systems. eggmanone. autoimmunity. controlled release. Medicine (General) R5-920
spellingShingle	advanced delivery systems. eggmanone. autoimmunity. controlled release. Medicine (General) R5-920 Haycook CP Balsamo JA Glass EB Williams CH Hong CC Major AS Giorgio TD PEGylated PLGA Nanoparticle Delivery of Eggmanone for T Cell Modulation: Applications in Rheumatic Autoimmunity
description	Christopher P Haycook,1 Joseph A Balsamo,2,3 Evan B Glass,1 Charles H Williams,4 Charles C Hong,5 Amy S Major,3,6 Todd D Giorgio1 1Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA; 2Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA; 3Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt Medical Center, Nashville, TN 37232, USA; 4Department of Medicine, Division of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; 5Department of Medicine, Division of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; 6U.S., Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, USACorrespondence: Todd D GiorgioDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USAEmail todd.d.giorgio@vanderbilt.eduBackground: Helper T cell activity is dysregulated in a number of diseases including those associated with rheumatic autoimmunity. Treatment options are limited and usually consist of systemic immune suppression, resulting in undesirable consequences from compromised immunity. Hedgehog (Hh) signaling has been implicated in the activation of T cells and the formation of the immune synapse, but remains understudied in the context of autoimmunity. Modulation of Hh signaling has the potential to enable controlled immunosuppression but a potential therapy has not yet been developed to leverage this opportunity.Methods: In this work, we developed biodegradable nanoparticles to enable targeted delivery of eggmanone (Egm), a specific Hh inhibitor, to CD4+ T cell subsets. We utilized two FDA-approved polymers, poly(lactic-co-glycolic acid) and polyethylene glycol, to generate hydrolytically degradable nanoparticles. Furthermore, we employed maleimide-thiol mediated conjugation chemistry to decorate nanoparticles with anti-CD4 F(ab’) antibody fragments to enable targeted delivery of Egm.Results: Our novel delivery system achieved a highly specific association with the majority of CD4+ T cells present among a complex cell population. Additionally, we have demonstrated antigen-specific inhibition of CD4+ T cell responses mediated by nanoparticle-formulated Egm.Conclusion: This work is the first characterization of Egm’s immunomodulatory potential. Importantly, this study also suggests the potential benefit of a biodegradable delivery vehicle that is rationally designed for preferential interaction with a specific immune cell subtype for targeted modulation of Hh signaling.Keywords: advanced delivery systems, eggmanone, autoimmunity, controlled release
format	article
author	Haycook CP Balsamo JA Glass EB Williams CH Hong CC Major AS Giorgio TD
author_facet	Haycook CP Balsamo JA Glass EB Williams CH Hong CC Major AS Giorgio TD
author_sort	Haycook CP
title	PEGylated PLGA Nanoparticle Delivery of Eggmanone for T Cell Modulation: Applications in Rheumatic Autoimmunity
title_short	PEGylated PLGA Nanoparticle Delivery of Eggmanone for T Cell Modulation: Applications in Rheumatic Autoimmunity
title_full	PEGylated PLGA Nanoparticle Delivery of Eggmanone for T Cell Modulation: Applications in Rheumatic Autoimmunity
title_fullStr	PEGylated PLGA Nanoparticle Delivery of Eggmanone for T Cell Modulation: Applications in Rheumatic Autoimmunity
title_full_unstemmed	PEGylated PLGA Nanoparticle Delivery of Eggmanone for T Cell Modulation: Applications in Rheumatic Autoimmunity
title_sort	pegylated plga nanoparticle delivery of eggmanone for t cell modulation: applications in rheumatic autoimmunity
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/6fcaf2fe36f44573a38100c04d2567fd
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PEGylated PLGA Nanoparticle Delivery of Eggmanone for T Cell Modulation: Applications in Rheumatic Autoimmunity

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