Intracellular redox-responsive nanocarrier for plasmid delivery: in vitro characterization and in vivo studies in mice

Lifen Zhang,1,2 Yushun Zhang,1,2 Zhenzhen Chen,3 Yuling He1 1State Key Laboratory of Applied Organic Chemistry, 2Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 3Department of Bioe...

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Autores principales:	Zhang L, Zhang Y, Chen Z, He Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Responsive gene delivery polycation Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5f3bffd7f86e4172aba1c3238ab419c5
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spelling	oai:doaj.org-article:5f3bffd7f86e4172aba1c3238ab419c52021-12-02T05:02:59ZIntracellular redox-responsive nanocarrier for plasmid delivery: in vitro characterization and in vivo studies in mice1178-2013https://doaj.org/article/5f3bffd7f86e4172aba1c3238ab419c52016-10-01T00:00:00Zhttps://www.dovepress.com/intracellular-redox-responsive-nanocarrier-for-plasmid-delivery-in-vit-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Lifen Zhang,1,2 Yushun Zhang,1,2 Zhenzhen Chen,3 Yuling He1 1State Key Laboratory of Applied Organic Chemistry, 2Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 3Department of Bioengineering, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China Abstract: Although some modifications of polyethyleneimine (PEI) properties have been explored to balance the transfection efficiency and cytotoxicity, its successful plasmid delivery in vitro and in vivo to realize its true therapeutic potentials remains a major challenge, mainly due to intracellular trafficking barriers. Herein, we present a delivery nanocarrier Pluronic-PEI-SS by conjugating reducible disulfide-linked PEI (PEI-SS) to biocompatible Pluronic for enhanced DNA delivery and transfection efficiency in vitro and in vivo. Pluronic-PEI-SS strongly condensed plasmid DNA to low positively charged nanocomplexes, exhibited good stability against deoxyribonuclease I digestion, and tended to be easily degraded in the presence of reducing agent 1,4-dithiothreitol. The in vitro transfection of the complex Pluronic-PEI-SS/DNA into HeLa and 293T cells resulted in lower cytotoxicity as well as significantly higher cellular uptake, nucleus transfection, and gene expression than Pluronic-PEI (25 kDa), PEI-SS, and PEI 25 kDa given alone. Furthermore, the in vivo transfection study demonstrated that Pluronic-PEI-SS/DNA complexes induced a higher enrichment than the commercial PEI/DNA complex in the tumor, indicating their potential application as biocompatible vector in gene delivery. Keywords: responsive, gene delivery, polycation, Pluronic, disulfide-linked Zhang LZhang YChen ZHe YDove Medical PressarticleResponsivegene deliverypolycationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 5245-5256 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Responsive gene delivery polycation Medicine (General) R5-920
spellingShingle	Responsive gene delivery polycation Medicine (General) R5-920 Zhang L Zhang Y Chen Z He Y Intracellular redox-responsive nanocarrier for plasmid delivery: in vitro characterization and in vivo studies in mice
description	Lifen Zhang,1,2 Yushun Zhang,1,2 Zhenzhen Chen,3 Yuling He1 1State Key Laboratory of Applied Organic Chemistry, 2Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 3Department of Bioengineering, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China Abstract: Although some modifications of polyethyleneimine (PEI) properties have been explored to balance the transfection efficiency and cytotoxicity, its successful plasmid delivery in vitro and in vivo to realize its true therapeutic potentials remains a major challenge, mainly due to intracellular trafficking barriers. Herein, we present a delivery nanocarrier Pluronic-PEI-SS by conjugating reducible disulfide-linked PEI (PEI-SS) to biocompatible Pluronic for enhanced DNA delivery and transfection efficiency in vitro and in vivo. Pluronic-PEI-SS strongly condensed plasmid DNA to low positively charged nanocomplexes, exhibited good stability against deoxyribonuclease I digestion, and tended to be easily degraded in the presence of reducing agent 1,4-dithiothreitol. The in vitro transfection of the complex Pluronic-PEI-SS/DNA into HeLa and 293T cells resulted in lower cytotoxicity as well as significantly higher cellular uptake, nucleus transfection, and gene expression than Pluronic-PEI (25 kDa), PEI-SS, and PEI 25 kDa given alone. Furthermore, the in vivo transfection study demonstrated that Pluronic-PEI-SS/DNA complexes induced a higher enrichment than the commercial PEI/DNA complex in the tumor, indicating their potential application as biocompatible vector in gene delivery. Keywords: responsive, gene delivery, polycation, Pluronic, disulfide-linked
format	article
author	Zhang L Zhang Y Chen Z He Y
author_facet	Zhang L Zhang Y Chen Z He Y
author_sort	Zhang L
title	Intracellular redox-responsive nanocarrier for plasmid delivery: in vitro characterization and in vivo studies in mice
title_short	Intracellular redox-responsive nanocarrier for plasmid delivery: in vitro characterization and in vivo studies in mice
title_full	Intracellular redox-responsive nanocarrier for plasmid delivery: in vitro characterization and in vivo studies in mice
title_fullStr	Intracellular redox-responsive nanocarrier for plasmid delivery: in vitro characterization and in vivo studies in mice
title_full_unstemmed	Intracellular redox-responsive nanocarrier for plasmid delivery: in vitro characterization and in vivo studies in mice
title_sort	intracellular redox-responsive nanocarrier for plasmid delivery: in vitro characterization and in vivo studies in mice
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/5f3bffd7f86e4172aba1c3238ab419c5
work_keys_str_mv	AT zhangl intracellularredoxresponsivenanocarrierforplasmiddeliveryinvitrocharacterizationandinvivostudiesinmice AT zhangy intracellularredoxresponsivenanocarrierforplasmiddeliveryinvitrocharacterizationandinvivostudiesinmice AT chenz intracellularredoxresponsivenanocarrierforplasmiddeliveryinvitrocharacterizationandinvivostudiesinmice AT hey intracellularredoxresponsivenanocarrierforplasmiddeliveryinvitrocharacterizationandinvivostudiesinmice
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Intracellular redox-responsive nanocarrier for plasmid delivery: in vitro characterization and in vivo studies in mice

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