Amphiphilic core shell nanoparticles containing dense polyethyleneimine shells for efficient delivery of microRNA to Kupffer cells

Zuojin Liu,1,* Dechao Niu,2,3,* Junyong Zhang,1 Wenfeng Zhang,1 Yuan Yao,2 Pei Li,2 Jianping Gong1 1Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 2Department of Applied Biology and Chemical Technology, The Hong Kon...

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Autores principales:	Liu Z, Niu D, Zhang J, Zhang W, Yao Y, Li P, Gong J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Branched polyethyleneimine Amphiphilic core-shell nanoparticles Kupffer cells Gene delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/3ddedc5fc56f4380abf9a3d37b5453b7
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spelling	oai:doaj.org-article:3ddedc5fc56f4380abf9a3d37b5453b72021-12-02T02:41:38ZAmphiphilic core shell nanoparticles containing dense polyethyleneimine shells for efficient delivery of microRNA to Kupffer cells1178-2013https://doaj.org/article/3ddedc5fc56f4380abf9a3d37b5453b72016-06-01T00:00:00Zhttps://www.dovepress.com/amphiphilic-core-shell-nanoparticles-containing-dense-polyethyleneimin-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Zuojin Liu,1,* Dechao Niu,2,3,* Junyong Zhang,1 Wenfeng Zhang,1 Yuan Yao,2 Pei Li,2 Jianping Gong1 1Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 2Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, 3Lab of Low-Dimensional Materials Chemistry, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Efficient and targeted delivery approach to transfer exogenous genes into macrophages is still a great challenge. Current gene delivery methods often result in low cellular uptake efficiency in vivo in some types of cells, especially for the Kupffer cells (KCs). In this article, we demonstrate that amphiphilic core–shell nanoparticles (NPs) consisting of well-defined hydrophobic poly(methyl methacrylate) (PMMA) cores and branched polyethyleneimine (PEI) shells (denoted as PEI@PMMA NPs) are efficient nanocarriers to deliver microRNA (miRNA)-loaded plasmid to the KCs. Average hydrodynamic diameter of PEI@PMMA NPs was 279 nm with a narrow size distribution. The NPs also possessed positive surface charges up to +30 mV in water, thus enabling effective condensation of negatively charged plasmid DNA. Gel electrophoresis assay showed that the resultant PEI@PMMA NPs were able to completely condense miRNA plasmid at a weight ratio of 25:1 (N/P ratio equal to 45:1). The Cell Counting Kit-8 assay and flow cytometry results showed that the PEI@PMMA/miRNA NPs displayed low cytotoxicity and cell apoptosis activity against the KCs. The maximum cell transfection efficiency reached 34.7% after 48 hours, which is much higher than that obtained by using the commercial Lipofectamine™ 2000 (1.7%). Bio-transmission electron microscope observation revealed that the PEI@PMMA NPs were mainly distributed in the cytoplasm of the KCs. Furthermore, when compared to the control groups, the protein expression of target nuclear factor κB P65 was considerably inhibited (P<0.05) both in vitro and in vivo. These results demonstrate that the PEI@PMMA NPs with a unique amphiphilic core–shell nanostructure are promising nanocarriers for delivering miRNA plasmid to KCs. Keywords: branched polyethyleneimine, amphiphilic core–shell nanoparticles, Kupffer cells, gene deliveryLiu ZNiu DZhang JZhang WYao YLi PGong JDove Medical PressarticleBranched polyethyleneimineAmphiphilic core-shell nanoparticlesKupffer cellsGene deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 2785-2797 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Branched polyethyleneimine Amphiphilic core-shell nanoparticles Kupffer cells Gene delivery Medicine (General) R5-920
spellingShingle	Branched polyethyleneimine Amphiphilic core-shell nanoparticles Kupffer cells Gene delivery Medicine (General) R5-920 Liu Z Niu D Zhang J Zhang W Yao Y Li P Gong J Amphiphilic core shell nanoparticles containing dense polyethyleneimine shells for efficient delivery of microRNA to Kupffer cells
description	Zuojin Liu,1,* Dechao Niu,2,3,* Junyong Zhang,1 Wenfeng Zhang,1 Yuan Yao,2 Pei Li,2 Jianping Gong1 1Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 2Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, 3Lab of Low-Dimensional Materials Chemistry, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Efficient and targeted delivery approach to transfer exogenous genes into macrophages is still a great challenge. Current gene delivery methods often result in low cellular uptake efficiency in vivo in some types of cells, especially for the Kupffer cells (KCs). In this article, we demonstrate that amphiphilic core–shell nanoparticles (NPs) consisting of well-defined hydrophobic poly(methyl methacrylate) (PMMA) cores and branched polyethyleneimine (PEI) shells (denoted as PEI@PMMA NPs) are efficient nanocarriers to deliver microRNA (miRNA)-loaded plasmid to the KCs. Average hydrodynamic diameter of PEI@PMMA NPs was 279 nm with a narrow size distribution. The NPs also possessed positive surface charges up to +30 mV in water, thus enabling effective condensation of negatively charged plasmid DNA. Gel electrophoresis assay showed that the resultant PEI@PMMA NPs were able to completely condense miRNA plasmid at a weight ratio of 25:1 (N/P ratio equal to 45:1). The Cell Counting Kit-8 assay and flow cytometry results showed that the PEI@PMMA/miRNA NPs displayed low cytotoxicity and cell apoptosis activity against the KCs. The maximum cell transfection efficiency reached 34.7% after 48 hours, which is much higher than that obtained by using the commercial Lipofectamine™ 2000 (1.7%). Bio-transmission electron microscope observation revealed that the PEI@PMMA NPs were mainly distributed in the cytoplasm of the KCs. Furthermore, when compared to the control groups, the protein expression of target nuclear factor κB P65 was considerably inhibited (P<0.05) both in vitro and in vivo. These results demonstrate that the PEI@PMMA NPs with a unique amphiphilic core–shell nanostructure are promising nanocarriers for delivering miRNA plasmid to KCs. Keywords: branched polyethyleneimine, amphiphilic core–shell nanoparticles, Kupffer cells, gene delivery
format	article
author	Liu Z Niu D Zhang J Zhang W Yao Y Li P Gong J
author_facet	Liu Z Niu D Zhang J Zhang W Yao Y Li P Gong J
author_sort	Liu Z
title	Amphiphilic core shell nanoparticles containing dense polyethyleneimine shells for efficient delivery of microRNA to Kupffer cells
title_short	Amphiphilic core shell nanoparticles containing dense polyethyleneimine shells for efficient delivery of microRNA to Kupffer cells
title_full	Amphiphilic core shell nanoparticles containing dense polyethyleneimine shells for efficient delivery of microRNA to Kupffer cells
title_fullStr	Amphiphilic core shell nanoparticles containing dense polyethyleneimine shells for efficient delivery of microRNA to Kupffer cells
title_full_unstemmed	Amphiphilic core shell nanoparticles containing dense polyethyleneimine shells for efficient delivery of microRNA to Kupffer cells
title_sort	amphiphilic core shell nanoparticles containing dense polyethyleneimine shells for efficient delivery of microrna to kupffer cells
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/3ddedc5fc56f4380abf9a3d37b5453b7
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Amphiphilic core shell nanoparticles containing dense polyethyleneimine shells for efficient delivery of microRNA to Kupffer cells

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