Stability and toxicity of empty or gene-loaded lipopolysaccharide-amine nanopolymersomes

Qinmei Wang,1,* Ying Chen,1,* Lichun Wang,1 Xinchun Zhang,2 Hongzhang Huang,2 Wei Teng2 1Key Laboratory on Assisted Circulation, Ministry of Health, Cardiovascular Division, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Hospital of Stomatology...

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Autores principales:	Wang QM, Chen Y, Wang LC, Zhang XC, Huang HZ, Teng W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5deb58ee0f5044baac7a6f46247063e6
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spelling	oai:doaj.org-article:5deb58ee0f5044baac7a6f46247063e62021-12-02T01:32:33ZStability and toxicity of empty or gene-loaded lipopolysaccharide-amine nanopolymersomes1178-2013https://doaj.org/article/5deb58ee0f5044baac7a6f46247063e62015-01-01T00:00:00Zhttp://www.dovepress.com/stability-and-toxicity-of-empty-or-gene-loaded-lipopolysaccharide-amin-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Qinmei Wang,1,* Ying Chen,1,* Lichun Wang,1 Xinchun Zhang,2 Hongzhang Huang,2 Wei Teng2 1Key Laboratory on Assisted Circulation, Ministry of Health, Cardiovascular Division, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Hospital of Stomatology, Institute of Stomatological Research, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Successful in vivo gene delivery mediated by nonviral vectors requires efficient extracellular and intracellular gene delivery, but few studies have given attention to the former. That is why numerous gene delivery systems have succeeded in vitro, while the expected clinical success has not come about. To realize efficient extracellular gene delivery, the stability of vectors and/or their complexes with genes in body fluids is first required, which prevents loaded genes from premature unloading and degradation. Furthermore, the storage stability of vectors under common conditions is important for their widespread applications. Lipopolysaccharide-amine nanopolymersomes (NPs), a gene vector developed by our group recently, have higher than 95% in vitro transfection efficiency in mesenchymal stem cells when delivering pEGFP, and induce significant angiogenesis in zebrafish when delivering plasmid encoding vascular endothelial growth factor deoxyribonucleic acid (pVEGF). To reveal their extracellular delivery ability and storage stability, in this study their stability in various simulant physiological environments and storage conditions was systematically studied by monitoring their changes in disassembly, size, zeta potential, and transfection efficiency. Additionally, damage to the mitochondria of mesenchymal stem cells was evaluated. Results show that NPs and plasmid deoxyribonucleic acid (pDNA)-loaded NPs (pNPs) have acceptable stability against dilution, anions, salts, pH, enzyme, and serum, presumably assuring their efficient extracellular delivery in vivo. Moreover, both the lyophilized NPs at room temperature and NP/pNP solution at 4°C have high storage stability, and pNPs show low damage to the mitochondria. The acceptable stability of NPs combined with compatibility and efficient gene transfection highlight their huge potential in the clinic as a gene delivery vector. Keywords: nanopolymersomes, extracellular delivery stability, storage stability, toxicity, polyethyleneimine, alginate, cholesterol, mesenchymal stem cellsWang QMChen YWang LCZhang XCHuang HZTeng WDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 597-608 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Wang QM Chen Y Wang LC Zhang XC Huang HZ Teng W Stability and toxicity of empty or gene-loaded lipopolysaccharide-amine nanopolymersomes
description	Qinmei Wang,1,* Ying Chen,1,* Lichun Wang,1 Xinchun Zhang,2 Hongzhang Huang,2 Wei Teng2 1Key Laboratory on Assisted Circulation, Ministry of Health, Cardiovascular Division, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Hospital of Stomatology, Institute of Stomatological Research, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Successful in vivo gene delivery mediated by nonviral vectors requires efficient extracellular and intracellular gene delivery, but few studies have given attention to the former. That is why numerous gene delivery systems have succeeded in vitro, while the expected clinical success has not come about. To realize efficient extracellular gene delivery, the stability of vectors and/or their complexes with genes in body fluids is first required, which prevents loaded genes from premature unloading and degradation. Furthermore, the storage stability of vectors under common conditions is important for their widespread applications. Lipopolysaccharide-amine nanopolymersomes (NPs), a gene vector developed by our group recently, have higher than 95% in vitro transfection efficiency in mesenchymal stem cells when delivering pEGFP, and induce significant angiogenesis in zebrafish when delivering plasmid encoding vascular endothelial growth factor deoxyribonucleic acid (pVEGF). To reveal their extracellular delivery ability and storage stability, in this study their stability in various simulant physiological environments and storage conditions was systematically studied by monitoring their changes in disassembly, size, zeta potential, and transfection efficiency. Additionally, damage to the mitochondria of mesenchymal stem cells was evaluated. Results show that NPs and plasmid deoxyribonucleic acid (pDNA)-loaded NPs (pNPs) have acceptable stability against dilution, anions, salts, pH, enzyme, and serum, presumably assuring their efficient extracellular delivery in vivo. Moreover, both the lyophilized NPs at room temperature and NP/pNP solution at 4°C have high storage stability, and pNPs show low damage to the mitochondria. The acceptable stability of NPs combined with compatibility and efficient gene transfection highlight their huge potential in the clinic as a gene delivery vector. Keywords: nanopolymersomes, extracellular delivery stability, storage stability, toxicity, polyethyleneimine, alginate, cholesterol, mesenchymal stem cells
format	article
author	Wang QM Chen Y Wang LC Zhang XC Huang HZ Teng W
author_facet	Wang QM Chen Y Wang LC Zhang XC Huang HZ Teng W
author_sort	Wang QM
title	Stability and toxicity of empty or gene-loaded lipopolysaccharide-amine nanopolymersomes
title_short	Stability and toxicity of empty or gene-loaded lipopolysaccharide-amine nanopolymersomes
title_full	Stability and toxicity of empty or gene-loaded lipopolysaccharide-amine nanopolymersomes
title_fullStr	Stability and toxicity of empty or gene-loaded lipopolysaccharide-amine nanopolymersomes
title_full_unstemmed	Stability and toxicity of empty or gene-loaded lipopolysaccharide-amine nanopolymersomes
title_sort	stability and toxicity of empty or gene-loaded lipopolysaccharide-amine nanopolymersomes
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/5deb58ee0f5044baac7a6f46247063e6
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Stability and toxicity of empty or gene-loaded lipopolysaccharide-amine nanopolymersomes

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