Cellular uptake mechanism and intracellular fate of hydrophobically modified pullulan nanoparticles

Liqin Jiang,1 Xuemin Li,1 Lingrong Liu,1 Qiqing Zhang1,21Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China; 2Research Center of Biomedical Engineering, Xiamen University, Xiamen, People's Rep...

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Autores principales: Jiang L, Li X, Liu L, Zhang Q
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Lenguaje:EN
Publicado: Dove Medical Press 2013
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Acceso en línea:https://doaj.org/article/dda69de2034d4ce1888f917caab94266
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spelling oai:doaj.org-article:dda69de2034d4ce1888f917caab942662021-12-02T00:33:06ZCellular uptake mechanism and intracellular fate of hydrophobically modified pullulan nanoparticles1176-91141178-2013https://doaj.org/article/dda69de2034d4ce1888f917caab942662013-05-01T00:00:00Zhttp://www.dovepress.com/cellular-uptake-mechanism-and-intracellular-fate-of-hydrophobically-mo-a12998https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Liqin Jiang,1 Xuemin Li,1 Lingrong Liu,1 Qiqing Zhang1,21Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China; 2Research Center of Biomedical Engineering, Xiamen University, Xiamen, People's Republic of ChinaAbstract: The cellular uptake mechanism and intracellular fate of self-assembled nanoparticles (NPs) of cholesterol-modified pullulan (CHSP) by human hepatocellular carcinoma (HepG2) cells were investigated. Covalent conjugation with fluorescein isothiocyanate (FITC) yielded stably labeled CHSP (FITC-CHSP), which was successfully formulated into NPs (mean particle size 63.0 ± 1.9 nm) by dialysis. A cytotoxicity assay clearly indicated that the CHSP NPs did not show significant toxicity in HepG2 cells. The effects of NP concentration, incubation time, and temperature on the cellular uptake of the NPs were systematically evaluated by fluorometry, and the results suggested that cellular uptake of the NPs was concentration-, time-, and temperature-dependent. In vitro experiments with endocytic inhibitors revealed that clathrin-mediated endocytosis and macropinocytosis were involved in the internalization of CHSP NPs. The intracellular trafficking study demonstrated that CHSP NPs were entrapped in the lysosomes at 1 hour after incubation; colocalization of NPs with either the Golgi apparatus or the endoplasmic reticula was not observed during the entire course of the study. These results suggested that the CHSP NPs may serve as a versatile carrier for intracellular delivery of therapeutic agents.Keywords: cholesterol-modified pullulan, self-assembled nanoparticles, FITC, endocytosis, intracellular traffickingJiang LLi XLiu LZhang QDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 1825-1834 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Jiang L
Li X
Liu L
Zhang Q
Cellular uptake mechanism and intracellular fate of hydrophobically modified pullulan nanoparticles
description Liqin Jiang,1 Xuemin Li,1 Lingrong Liu,1 Qiqing Zhang1,21Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China; 2Research Center of Biomedical Engineering, Xiamen University, Xiamen, People's Republic of ChinaAbstract: The cellular uptake mechanism and intracellular fate of self-assembled nanoparticles (NPs) of cholesterol-modified pullulan (CHSP) by human hepatocellular carcinoma (HepG2) cells were investigated. Covalent conjugation with fluorescein isothiocyanate (FITC) yielded stably labeled CHSP (FITC-CHSP), which was successfully formulated into NPs (mean particle size 63.0 ± 1.9 nm) by dialysis. A cytotoxicity assay clearly indicated that the CHSP NPs did not show significant toxicity in HepG2 cells. The effects of NP concentration, incubation time, and temperature on the cellular uptake of the NPs were systematically evaluated by fluorometry, and the results suggested that cellular uptake of the NPs was concentration-, time-, and temperature-dependent. In vitro experiments with endocytic inhibitors revealed that clathrin-mediated endocytosis and macropinocytosis were involved in the internalization of CHSP NPs. The intracellular trafficking study demonstrated that CHSP NPs were entrapped in the lysosomes at 1 hour after incubation; colocalization of NPs with either the Golgi apparatus or the endoplasmic reticula was not observed during the entire course of the study. These results suggested that the CHSP NPs may serve as a versatile carrier for intracellular delivery of therapeutic agents.Keywords: cholesterol-modified pullulan, self-assembled nanoparticles, FITC, endocytosis, intracellular trafficking
format article
author Jiang L
Li X
Liu L
Zhang Q
author_facet Jiang L
Li X
Liu L
Zhang Q
author_sort Jiang L
title Cellular uptake mechanism and intracellular fate of hydrophobically modified pullulan nanoparticles
title_short Cellular uptake mechanism and intracellular fate of hydrophobically modified pullulan nanoparticles
title_full Cellular uptake mechanism and intracellular fate of hydrophobically modified pullulan nanoparticles
title_fullStr Cellular uptake mechanism and intracellular fate of hydrophobically modified pullulan nanoparticles
title_full_unstemmed Cellular uptake mechanism and intracellular fate of hydrophobically modified pullulan nanoparticles
title_sort cellular uptake mechanism and intracellular fate of hydrophobically modified pullulan nanoparticles
publisher Dove Medical Press
publishDate 2013
url https://doaj.org/article/dda69de2034d4ce1888f917caab94266
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AT liul cellularuptakemechanismandintracellularfateofhydrophobicallymodifiedpullulannanoparticles
AT zhangq cellularuptakemechanismandintracellularfateofhydrophobicallymodifiedpullulannanoparticles
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