Cationic lipid-coated PEI/DNA polyplexes with improved efficiency and reduced cytotoxicity for gene delivery into mesenchymal stem cells

Hongmei Song, Gang Wang, Bin He, Li Li, Caixia Li, Yusi Lai, Xianghui Xu, Zhongwei GuNational Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, People&#39;s Republic of ChinaBackground: Effective gene transfection without serum deprivation is a prerequisite...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Song HM, Wang G, He B, Li L, Li CX, Lai YS, Xu XH, Gu ZW
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/4c875938200a4670a2d4147a1173fc81
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4c875938200a4670a2d4147a1173fc81
record_format	dspace
spelling	oai:doaj.org-article:4c875938200a4670a2d4147a1173fc812021-12-02T02:10:34ZCationic lipid-coated PEI/DNA polyplexes with improved efficiency and reduced cytotoxicity for gene delivery into mesenchymal stem cells1176-91141178-2013https://doaj.org/article/4c875938200a4670a2d4147a1173fc812012-08-01T00:00:00Zhttp://www.dovepress.com/cationic-lipid-coated-peidna-polyplexes-with-improved-efficiency-and-r-a10767https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Hongmei Song, Gang Wang, Bin He, Li Li, Caixia Li, Yusi Lai, Xianghui Xu, Zhongwei GuNational Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, People&#39;s Republic of ChinaBackground: Effective gene transfection without serum deprivation is a prerequisite for successful stem cell-based gene therapy. Polyethylenimine (PEI) is an efficient nonviral gene vector, but its application has been hindered by serum sensitivity and severe cytotoxicity.Methods: To solve this problem, a new family of lipopolyplexes was developed by coating PEI/DNA polyplexes with three serum-resistant cationic lipids, namely, lysinylated, histidylated, and arginylated cholesterol. The physical properties, transfection efficiency, cellular uptake, subcellular distribution, and cytotoxicity of the lipopolyplexes was investigated.Results: The outer coat composed of lysinylated or histidylated cholesterol remarkably improved the transfection efficiency of the polyplex with a low PEI/DNA ratio of 2 in the presence of serum. The resulting lysinylated and histidylated cholesterol lipopolyplexes were even more efficient than the best performing polyplex with a high PEI/DNA ratio of 10. Results from cellular uptake and subcellular distribution studies suggest that their higher transfection efficiency may result from accelerated DNA nuclear localization. The superiority of the lipopolyplexes over the best performing polyplex was also confirmed by delivering the therapeutic gene, hVEGF165. Equally importantly, the lipid coating removed the necessity of introducing excess free PEI chains into the transfection solution for higher efficiency, generating lipopolyplexes with no signs of cytotoxicity.Conclusion: Noncovalent modification of polyplexes with lysinylated and histidylated cholesterol lipids can simultaneously improve efficiency and reduce the toxicity of gene delivery under serum conditions, showing great promise for genetic modification of bone marrow stem cells.Keywords: gene delivery, nonviral vectors, cationic lipids, polyethylenimine, lipopolyplex, bone marrow stem cellsSong HMWang GHe BLi LLi CXLai YSXu XHGu ZWDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 4637-4648 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Song HM Wang G He B Li L Li CX Lai YS Xu XH Gu ZW Cationic lipid-coated PEI/DNA polyplexes with improved efficiency and reduced cytotoxicity for gene delivery into mesenchymal stem cells
description	Hongmei Song, Gang Wang, Bin He, Li Li, Caixia Li, Yusi Lai, Xianghui Xu, Zhongwei GuNational Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, People&#39;s Republic of ChinaBackground: Effective gene transfection without serum deprivation is a prerequisite for successful stem cell-based gene therapy. Polyethylenimine (PEI) is an efficient nonviral gene vector, but its application has been hindered by serum sensitivity and severe cytotoxicity.Methods: To solve this problem, a new family of lipopolyplexes was developed by coating PEI/DNA polyplexes with three serum-resistant cationic lipids, namely, lysinylated, histidylated, and arginylated cholesterol. The physical properties, transfection efficiency, cellular uptake, subcellular distribution, and cytotoxicity of the lipopolyplexes was investigated.Results: The outer coat composed of lysinylated or histidylated cholesterol remarkably improved the transfection efficiency of the polyplex with a low PEI/DNA ratio of 2 in the presence of serum. The resulting lysinylated and histidylated cholesterol lipopolyplexes were even more efficient than the best performing polyplex with a high PEI/DNA ratio of 10. Results from cellular uptake and subcellular distribution studies suggest that their higher transfection efficiency may result from accelerated DNA nuclear localization. The superiority of the lipopolyplexes over the best performing polyplex was also confirmed by delivering the therapeutic gene, hVEGF165. Equally importantly, the lipid coating removed the necessity of introducing excess free PEI chains into the transfection solution for higher efficiency, generating lipopolyplexes with no signs of cytotoxicity.Conclusion: Noncovalent modification of polyplexes with lysinylated and histidylated cholesterol lipids can simultaneously improve efficiency and reduce the toxicity of gene delivery under serum conditions, showing great promise for genetic modification of bone marrow stem cells.Keywords: gene delivery, nonviral vectors, cationic lipids, polyethylenimine, lipopolyplex, bone marrow stem cells
format	article
author	Song HM Wang G He B Li L Li CX Lai YS Xu XH Gu ZW
author_facet	Song HM Wang G He B Li L Li CX Lai YS Xu XH Gu ZW
author_sort	Song HM
title	Cationic lipid-coated PEI/DNA polyplexes with improved efficiency and reduced cytotoxicity for gene delivery into mesenchymal stem cells
title_short	Cationic lipid-coated PEI/DNA polyplexes with improved efficiency and reduced cytotoxicity for gene delivery into mesenchymal stem cells
title_full	Cationic lipid-coated PEI/DNA polyplexes with improved efficiency and reduced cytotoxicity for gene delivery into mesenchymal stem cells
title_fullStr	Cationic lipid-coated PEI/DNA polyplexes with improved efficiency and reduced cytotoxicity for gene delivery into mesenchymal stem cells
title_full_unstemmed	Cationic lipid-coated PEI/DNA polyplexes with improved efficiency and reduced cytotoxicity for gene delivery into mesenchymal stem cells
title_sort	cationic lipid-coated pei/dna polyplexes with improved efficiency and reduced cytotoxicity for gene delivery into mesenchymal stem cells
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/4c875938200a4670a2d4147a1173fc81
work_keys_str_mv	AT songhm cationiclipidcoatedpeidnapolyplexeswithimprovedefficiencyandreducedcytotoxicityforgenedeliveryintomesenchymalstemcells AT wangg cationiclipidcoatedpeidnapolyplexeswithimprovedefficiencyandreducedcytotoxicityforgenedeliveryintomesenchymalstemcells AT heb cationiclipidcoatedpeidnapolyplexeswithimprovedefficiencyandreducedcytotoxicityforgenedeliveryintomesenchymalstemcells AT lil cationiclipidcoatedpeidnapolyplexeswithimprovedefficiencyandreducedcytotoxicityforgenedeliveryintomesenchymalstemcells AT licx cationiclipidcoatedpeidnapolyplexeswithimprovedefficiencyandreducedcytotoxicityforgenedeliveryintomesenchymalstemcells AT laiys cationiclipidcoatedpeidnapolyplexeswithimprovedefficiencyandreducedcytotoxicityforgenedeliveryintomesenchymalstemcells AT xuxh cationiclipidcoatedpeidnapolyplexeswithimprovedefficiencyandreducedcytotoxicityforgenedeliveryintomesenchymalstemcells AT guzw cationiclipidcoatedpeidnapolyplexeswithimprovedefficiencyandreducedcytotoxicityforgenedeliveryintomesenchymalstemcells
_version_	1718402647120150528

Cationic lipid-coated PEI/DNA polyplexes with improved efficiency and reduced cytotoxicity for gene delivery into mesenchymal stem cells

Ejemplares similares