Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport

Li Qun Jiang,1 Ting Yu Wang,1 Thomas J Webster,2 Hua-Jian Duan,1 Jing Ying Qiu,1 Zi Ming Zhao,1 Xiao Xing Yin,1,* Chun Li Zheng3,* 1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Depart...

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Autores principales:	Jiang LQ, Wang TY, Webster TJ, Duan HJ, Qiu JY, Zhao ZM, Yin XX, Zheng CL
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	exocytosis uptake intercellular transport chitosan nanoparticles macrophages Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0e6b53a495a145ffac99c702d34d13ae
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spelling	oai:doaj.org-article:0e6b53a495a145ffac99c702d34d13ae2021-12-02T02:53:20ZIntracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport1178-2013https://doaj.org/article/0e6b53a495a145ffac99c702d34d13ae2017-08-01T00:00:00Zhttps://www.dovepress.com/intracellular-disposition-of-chitosan-nanoparticles-in-macrophages-int-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Li Qun Jiang,1 Ting Yu Wang,1 Thomas J Webster,2 Hua-Jian Duan,1 Jing Ying Qiu,1 Zi Ming Zhao,1 Xiao Xing Yin,1,* Chun Li Zheng3,* 1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 3School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: Biodegradable nanomaterials have been widely used in numerous medical fields. To further improve such efforts, this study focused on the intracellular disposition of chitosan nanoparticles (CsNPs) in macrophages, a primary cell of the mononuclear phagocyte system (MPS). Such interactions with the MPS determine the nanoparticle retention time in the body and consequently play a significant role in their own clinical safety. In this study, various dye-labeled CsNPs (about 250 nm) were prepared, and a murine macrophage cell line (RAW 264.7) was selected as a model macrophage. The results showed two mechanisms of macrophage incorporation of CsNPs, ie, a clathrin-mediated endocytosis pathway (the primary) and phagocytosis. Following internalization, the particles partly dissociated in the cells, indicating cellular digestion of the nanoparticles. It was proved that, after intracellular uptake, a large proportion of CsNPs were exocytosed within 24 h; this excretion induced a decrease in fluorescence intensity in cells by 69%, with the remaining particles possessing difficulty being cleared. Exocytosis could be inhibited by both wortmannin and vacuolin-1, indicating that CsNP uptake was mediated by lysosomal and multivesicular body pathways, and after exocytosis, the reuptake of CsNPs by neighboring cells was verified by further experiments. This study, thus, elucidated the fate of CsNPs in macrophages as well as identified cellular disposition mechanisms, providing the basis for how CsNPs are recognized by the MPS; such information is crucial to numerous medical applications of CsNPs. Keywords: exocytosis, uptake, intercellular transport, chitosan nanoparticles, macrophagesJiang LQWang TYWebster TJDuan HJQiu JYZhao ZMYin XXZheng CLDove Medical Pressarticleexocytosisuptakeintercellular transportchitosan nanoparticlesmacrophagesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 6383-6398 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	exocytosis uptake intercellular transport chitosan nanoparticles macrophages Medicine (General) R5-920
spellingShingle	exocytosis uptake intercellular transport chitosan nanoparticles macrophages Medicine (General) R5-920 Jiang LQ Wang TY Webster TJ Duan HJ Qiu JY Zhao ZM Yin XX Zheng CL Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport
description	Li Qun Jiang,1 Ting Yu Wang,1 Thomas J Webster,2 Hua-Jian Duan,1 Jing Ying Qiu,1 Zi Ming Zhao,1 Xiao Xing Yin,1,* Chun Li Zheng3,* 1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 3School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: Biodegradable nanomaterials have been widely used in numerous medical fields. To further improve such efforts, this study focused on the intracellular disposition of chitosan nanoparticles (CsNPs) in macrophages, a primary cell of the mononuclear phagocyte system (MPS). Such interactions with the MPS determine the nanoparticle retention time in the body and consequently play a significant role in their own clinical safety. In this study, various dye-labeled CsNPs (about 250 nm) were prepared, and a murine macrophage cell line (RAW 264.7) was selected as a model macrophage. The results showed two mechanisms of macrophage incorporation of CsNPs, ie, a clathrin-mediated endocytosis pathway (the primary) and phagocytosis. Following internalization, the particles partly dissociated in the cells, indicating cellular digestion of the nanoparticles. It was proved that, after intracellular uptake, a large proportion of CsNPs were exocytosed within 24 h; this excretion induced a decrease in fluorescence intensity in cells by 69%, with the remaining particles possessing difficulty being cleared. Exocytosis could be inhibited by both wortmannin and vacuolin-1, indicating that CsNP uptake was mediated by lysosomal and multivesicular body pathways, and after exocytosis, the reuptake of CsNPs by neighboring cells was verified by further experiments. This study, thus, elucidated the fate of CsNPs in macrophages as well as identified cellular disposition mechanisms, providing the basis for how CsNPs are recognized by the MPS; such information is crucial to numerous medical applications of CsNPs. Keywords: exocytosis, uptake, intercellular transport, chitosan nanoparticles, macrophages
format	article
author	Jiang LQ Wang TY Webster TJ Duan HJ Qiu JY Zhao ZM Yin XX Zheng CL
author_facet	Jiang LQ Wang TY Webster TJ Duan HJ Qiu JY Zhao ZM Yin XX Zheng CL
author_sort	Jiang LQ
title	Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport
title_short	Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport
title_full	Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport
title_fullStr	Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport
title_full_unstemmed	Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport
title_sort	intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/0e6b53a495a145ffac99c702d34d13ae
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Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport

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