Effect of CCR2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction

Jinli Wang,1,2,* Min Jeong Seo,1,* Michael B Deci,1 Brian R Weil,3 John M Canty,3,4 Juliane Nguyen1,2 1Department of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, NY, USA; 2Department of Biomedical Engineering, University at Buffalo,...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Wang J, Seo MJ, Deci MB, Weil BR, Canty JM, Nguyen J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	CCR2 inflammatory monocytes micelles myocardial infarction Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5346373363bf410bb5a85024c823324e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5346373363bf410bb5a85024c823324e
record_format	dspace
spelling	oai:doaj.org-article:5346373363bf410bb5a85024c823324e2021-12-02T01:48:32ZEffect of CCR2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction1178-2013https://doaj.org/article/5346373363bf410bb5a85024c823324e2018-10-01T00:00:00Zhttps://www.dovepress.com/effect-of-ccr2-inhibitor-loaded-lipid-micelles-on-inflammatory-cell-mi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jinli Wang,1,2,* Min Jeong Seo,1,* Michael B Deci,1 Brian R Weil,3 John M Canty,3,4 Juliane Nguyen1,2 1Department of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, NY, USA; 2Department of Biomedical Engineering, University at Buffalo, The State University of New York, Buffalo, NY, USA; 3Department of Medicine, Department of Physiology and Biophysics, Department of Biomedical Engineering, The Clinical and Translational Research Center, University at Buffalo, Buffalo, NY, USA; 4VA Western New York Healthcare System, Buffalo, NY, USA *These authors contributed equally to this work Background: After myocardial infarction (MI), inflammatory cells infiltrate the infarcted heart in response to secreted stimuli. Monocytes are recruited to the infarct via CCR2 chemokine receptors along a CCL2 concentration gradient. While infiltration of injured tissue with monocytes is an important component of the reparatory response, excessive or prolonged inflammation can adversely affect left ventricular remodeling and worsen clinical outcomes.Materials and methods: Here, we developed poly(ethylene glycol) (PEG)-distearoylphosphatidylethanolamine (PEG-DSPE) micelles loaded with a small molecule CCR2 antagonist to inhibit monocyte recruitment to the infarcted myocardium. To specifically target CCR2-expressing cells, PEG-DSPE micelles were further surface decorated with an anti-CCR2 antibody.Results: Targeted PEG-DSPE micelles showed eight-fold greater binding to CCR2-expressing RAW 264.7 monocytes than plain, non-targeted PEG-DSPE micelles. In a mouse model of MI, CCR2-targeting PEG-DSPE micelles loaded with a CCR2 small molecule antagonist significantly decreased the number of Ly6Chigh inflammatory cells to 3% of total compared with PBS-treated controls. Furthermore, CCR2-targeting PEG-DSPE micelles significantly reduced the infarct size based on epicardial and endocardial infarct arc lengths.Conclusion: Both non-targeted and CCR2-targeting PEG-DSPE micelles showed a trend toward improving cardiac function. As such, PEG-DSPE micelles represent a promising cardiac therapeutic platform. Keywords: CCR2, inflammatory monocytes, micelles, myocardial infarctionWang JSeo MJDeci MBWeil BRCanty JMNguyen JDove Medical PressarticleCCR2inflammatory monocytesmicellesmyocardial infarctionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 6441-6451 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	CCR2 inflammatory monocytes micelles myocardial infarction Medicine (General) R5-920
spellingShingle	CCR2 inflammatory monocytes micelles myocardial infarction Medicine (General) R5-920 Wang J Seo MJ Deci MB Weil BR Canty JM Nguyen J Effect of CCR2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction
description	Jinli Wang,1,2,* Min Jeong Seo,1,* Michael B Deci,1 Brian R Weil,3 John M Canty,3,4 Juliane Nguyen1,2 1Department of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, NY, USA; 2Department of Biomedical Engineering, University at Buffalo, The State University of New York, Buffalo, NY, USA; 3Department of Medicine, Department of Physiology and Biophysics, Department of Biomedical Engineering, The Clinical and Translational Research Center, University at Buffalo, Buffalo, NY, USA; 4VA Western New York Healthcare System, Buffalo, NY, USA *These authors contributed equally to this work Background: After myocardial infarction (MI), inflammatory cells infiltrate the infarcted heart in response to secreted stimuli. Monocytes are recruited to the infarct via CCR2 chemokine receptors along a CCL2 concentration gradient. While infiltration of injured tissue with monocytes is an important component of the reparatory response, excessive or prolonged inflammation can adversely affect left ventricular remodeling and worsen clinical outcomes.Materials and methods: Here, we developed poly(ethylene glycol) (PEG)-distearoylphosphatidylethanolamine (PEG-DSPE) micelles loaded with a small molecule CCR2 antagonist to inhibit monocyte recruitment to the infarcted myocardium. To specifically target CCR2-expressing cells, PEG-DSPE micelles were further surface decorated with an anti-CCR2 antibody.Results: Targeted PEG-DSPE micelles showed eight-fold greater binding to CCR2-expressing RAW 264.7 monocytes than plain, non-targeted PEG-DSPE micelles. In a mouse model of MI, CCR2-targeting PEG-DSPE micelles loaded with a CCR2 small molecule antagonist significantly decreased the number of Ly6Chigh inflammatory cells to 3% of total compared with PBS-treated controls. Furthermore, CCR2-targeting PEG-DSPE micelles significantly reduced the infarct size based on epicardial and endocardial infarct arc lengths.Conclusion: Both non-targeted and CCR2-targeting PEG-DSPE micelles showed a trend toward improving cardiac function. As such, PEG-DSPE micelles represent a promising cardiac therapeutic platform. Keywords: CCR2, inflammatory monocytes, micelles, myocardial infarction
format	article
author	Wang J Seo MJ Deci MB Weil BR Canty JM Nguyen J
author_facet	Wang J Seo MJ Deci MB Weil BR Canty JM Nguyen J
author_sort	Wang J
title	Effect of CCR2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction
title_short	Effect of CCR2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction
title_full	Effect of CCR2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction
title_fullStr	Effect of CCR2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction
title_full_unstemmed	Effect of CCR2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction
title_sort	effect of ccr2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/5346373363bf410bb5a85024c823324e
work_keys_str_mv	AT wangj effectofccr2inhibitorloadedlipidmicellesoninflammatorycellmigrationandcardiacfunctionaftermyocardialinfarction AT seomj effectofccr2inhibitorloadedlipidmicellesoninflammatorycellmigrationandcardiacfunctionaftermyocardialinfarction AT decimb effectofccr2inhibitorloadedlipidmicellesoninflammatorycellmigrationandcardiacfunctionaftermyocardialinfarction AT weilbr effectofccr2inhibitorloadedlipidmicellesoninflammatorycellmigrationandcardiacfunctionaftermyocardialinfarction AT cantyjm effectofccr2inhibitorloadedlipidmicellesoninflammatorycellmigrationandcardiacfunctionaftermyocardialinfarction AT nguyenj effectofccr2inhibitorloadedlipidmicellesoninflammatorycellmigrationandcardiacfunctionaftermyocardialinfarction
_version_	1718402895684042752

Effect of CCR2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction

Ejemplares similares