Controllably local gene delivery mediated by polyelectrolyte multilayer films assembled from gene-loaded nanopolymersomes and hyaluronic acid

Wei Teng,1,* Qinmei Wang,2,* Ying Chen,2 Hongzhang Huang1 1Hospital of Stomatology, Institute of Stomatological Research, Guanghua School of Stomatology, Guangzhou, People’s Republic of China; 2Key Laboratory on Assisted Circulation, Ministry of Health, Cardiovascular Division, First Aff...

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Autores principales:	Teng W, Wang QM, Chen Y, Huang HZ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7750ad928f7b4e75a2b9b0721bd84693
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spelling	oai:doaj.org-article:7750ad928f7b4e75a2b9b0721bd846932021-12-02T02:10:31ZControllably local gene delivery mediated by polyelectrolyte multilayer films assembled from gene-loaded nanopolymersomes and hyaluronic acid1178-2013https://doaj.org/article/7750ad928f7b4e75a2b9b0721bd846932014-10-01T00:00:00Zhttp://www.dovepress.com/controllably-local-gene-delivery-mediated-by-polyelectrolyte-multilaye-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Wei Teng,1,* Qinmei Wang,2,* Ying Chen,2 Hongzhang Huang1 1Hospital of Stomatology, Institute of Stomatological Research, Guanghua School of Stomatology, Guangzhou, People’s Republic of China; 2Key Laboratory on Assisted Circulation, Ministry of Health, Cardiovascular Division, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: To explore a spatiotemporally controllable gene delivery system with high efficiency and safety, polyelectrolyte multilayer (PEM) films were constructed on titanium or quartz substrates via layer-by-layer self-assembly technique by using plasmid deoxyribonucleic acid-loaded lipopolysaccharide–amine nanopolymersomes (pNPs) as polycations and hyaluronic acid (HA) as polyanions. pNPs were chosen because they have high transfection efficiency (>95%) in mesenchymal stem cells (MSCs) and induce significant angiogenesis in zebrafish in conventional bolus transfection. The assembly process of PEM films was confirmed by analyses of quartz crystal microbalance with dissipation, X-ray photoelectron spectroscopy, infrared, contact angle, and zeta potential along with atomic force microscopy observation. Quartz crystal microbalance with dissipation analysis reveals that this film grows in an exponential mode, pNPs are the main contributor to the film mass, and the film mass can be modulated in a relatively wide range (1.0–29 µg/cm2) by adjusting the deposition layer number. Atomic force microscopy observation shows that the assembly leads to the formation of a patterned film with three-dimensional tree-like nanostructure, where the branches are composed of beaded chains (pNP beads are strung on HA molecular chains), and the incorporated pNPs keep structure intact. In vitro release experiment shows that plasmid deoxyribonucleic acid can be gradually released from films over 14 days, and the released plasmid deoxyribonucleic acid exists in a complex form. In vitro cell experiments demonstrate that PEM films can enhance the adhesion and proliferation of MSCs and efficiently transfect MSCs in situ in vitro for at least 4 days. Our results suggest that a (pNPs/HA)n system can mediate efficient transfection in stem cells in a spatially and temporally controllable pattern, highlighting its huge potential in local gene therapy. Keywords: localized gene delivery, layer-by-layer self-assembly, gene-loaded nanopolymersomes, hyaluronic acid, polyelectrolyte multilayer films, mesenchymal stem cellsTeng WWang QMChen YHuang HZDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 5013-5024 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Teng W Wang QM Chen Y Huang HZ Controllably local gene delivery mediated by polyelectrolyte multilayer films assembled from gene-loaded nanopolymersomes and hyaluronic acid
description	Wei Teng,1,* Qinmei Wang,2,* Ying Chen,2 Hongzhang Huang1 1Hospital of Stomatology, Institute of Stomatological Research, Guanghua School of Stomatology, Guangzhou, People’s Republic of China; 2Key Laboratory on Assisted Circulation, Ministry of Health, Cardiovascular Division, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: To explore a spatiotemporally controllable gene delivery system with high efficiency and safety, polyelectrolyte multilayer (PEM) films were constructed on titanium or quartz substrates via layer-by-layer self-assembly technique by using plasmid deoxyribonucleic acid-loaded lipopolysaccharide–amine nanopolymersomes (pNPs) as polycations and hyaluronic acid (HA) as polyanions. pNPs were chosen because they have high transfection efficiency (>95%) in mesenchymal stem cells (MSCs) and induce significant angiogenesis in zebrafish in conventional bolus transfection. The assembly process of PEM films was confirmed by analyses of quartz crystal microbalance with dissipation, X-ray photoelectron spectroscopy, infrared, contact angle, and zeta potential along with atomic force microscopy observation. Quartz crystal microbalance with dissipation analysis reveals that this film grows in an exponential mode, pNPs are the main contributor to the film mass, and the film mass can be modulated in a relatively wide range (1.0–29 µg/cm2) by adjusting the deposition layer number. Atomic force microscopy observation shows that the assembly leads to the formation of a patterned film with three-dimensional tree-like nanostructure, where the branches are composed of beaded chains (pNP beads are strung on HA molecular chains), and the incorporated pNPs keep structure intact. In vitro release experiment shows that plasmid deoxyribonucleic acid can be gradually released from films over 14 days, and the released plasmid deoxyribonucleic acid exists in a complex form. In vitro cell experiments demonstrate that PEM films can enhance the adhesion and proliferation of MSCs and efficiently transfect MSCs in situ in vitro for at least 4 days. Our results suggest that a (pNPs/HA)n system can mediate efficient transfection in stem cells in a spatially and temporally controllable pattern, highlighting its huge potential in local gene therapy. Keywords: localized gene delivery, layer-by-layer self-assembly, gene-loaded nanopolymersomes, hyaluronic acid, polyelectrolyte multilayer films, mesenchymal stem cells
format	article
author	Teng W Wang QM Chen Y Huang HZ
author_facet	Teng W Wang QM Chen Y Huang HZ
author_sort	Teng W
title	Controllably local gene delivery mediated by polyelectrolyte multilayer films assembled from gene-loaded nanopolymersomes and hyaluronic acid
title_short	Controllably local gene delivery mediated by polyelectrolyte multilayer films assembled from gene-loaded nanopolymersomes and hyaluronic acid
title_full	Controllably local gene delivery mediated by polyelectrolyte multilayer films assembled from gene-loaded nanopolymersomes and hyaluronic acid
title_fullStr	Controllably local gene delivery mediated by polyelectrolyte multilayer films assembled from gene-loaded nanopolymersomes and hyaluronic acid
title_full_unstemmed	Controllably local gene delivery mediated by polyelectrolyte multilayer films assembled from gene-loaded nanopolymersomes and hyaluronic acid
title_sort	controllably local gene delivery mediated by polyelectrolyte multilayer films assembled from gene-loaded nanopolymersomes and hyaluronic acid
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/7750ad928f7b4e75a2b9b0721bd84693
work_keys_str_mv	AT tengw controllablylocalgenedeliverymediatedbypolyelectrolytemultilayerfilmsassembledfromgeneloadednanopolymersomesandhyaluronicacid AT wangqm controllablylocalgenedeliverymediatedbypolyelectrolytemultilayerfilmsassembledfromgeneloadednanopolymersomesandhyaluronicacid AT cheny controllablylocalgenedeliverymediatedbypolyelectrolytemultilayerfilmsassembledfromgeneloadednanopolymersomesandhyaluronicacid AT huanghz controllablylocalgenedeliverymediatedbypolyelectrolytemultilayerfilmsassembledfromgeneloadednanopolymersomesandhyaluronicacid
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Controllably local gene delivery mediated by polyelectrolyte multilayer films assembled from gene-loaded nanopolymersomes and hyaluronic acid

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