Nuclear entry of hyperbranched polylysine nanoparticles into cochlear cells

Weikai Zhang1, Ya Zhang1, Marian L&ouml;bler2, Klaus-Peter Schmitz2, Aqeel Ahmad3, Ilmari Pyykk&ouml;1, Jing Zou11Department of Otolaryngology, University of Tampere, Medical School, Tampere, Finland; 2University of Rostock, Institute for Biomedical Engineering, Rostock, Germany; 3De...

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Autores principales:	Weikai Zhang, Ya Zhang, Marian L&ouml;bler, et al
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a4e277944d16466394501365354c0ad5
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spelling	oai:doaj.org-article:a4e277944d16466394501365354c0ad52021-12-02T04:20:59ZNuclear entry of hyperbranched polylysine nanoparticles into cochlear cells1176-91141178-2013https://doaj.org/article/a4e277944d16466394501365354c0ad52011-03-01T00:00:00Zhttp://www.dovepress.com/nuclear-entry-of-hyperbranched-polylysine-nanoparticles-into-cochlear--a6663https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Weikai Zhang1, Ya Zhang1, Marian L&ouml;bler2, Klaus-Peter Schmitz2, Aqeel Ahmad3, Ilmari Pyykk&ouml;1, Jing Zou11Department of Otolaryngology, University of Tampere, Medical School, Tampere, Finland; 2University of Rostock, Institute for Biomedical Engineering, Rostock, Germany; 3Department of Biomedical Engineering and Computational Science, Aalto University, Espoo, FinlandBackground: Gene therapy is a potentially effective therapeutic modality for treating sensorineural hearing loss. Nonviral gene delivery vectors are expected to become extremely safe and convenient, and nanoparticles are the most promising types of vectors. However, infrequent nuclear localization in the cochlear cells limits their application for gene therapy. This study aimed to investigate the potential nuclear entry of hyperbranched polylysine nanoparticles (HPNPs) for gene delivery to cochlear targets.Methods: Rat primary cochlear cells and cochlear explants generated from newborn rats were treated with different concentrations of HPNPs. For the in vivo study, HPNPs were administered to the rats&#39; round window membranes. Subcellular distribution of HPNPs in different cell populations was observed with confocal microscope 24 hours after administration.Results: Nuclear entry was observed in various cochlear cell types in vitro and in vivo. In the primary cochlear cell culture, concentration-dependent internalization was observed. In the cochlear organotypic culture, abundant HPNPs were found in the modiolus, including the spiral ganglion, organ of Corti, and lateral wall tissues. In the in vivo study, a gradient distribution of HPNPs through different layers of the round window membrane was observed. HPNPs were also distributed in the cells of the middle ear tissue. Additionally, efficient internalization of HPNPs was observed in the organ of Corti and spiral ganglion cells. In primary cochlear cells, HPNPs induced higher transfection efficiency than did LipofectamineTM.Conclusion: These results suggest that HPNPs are potentially an ideal carrier for gene delivery into the cochlea.Keywords: gene therapy, hearing loss, cochlea, internalization, nanoparticles, nuclear localization Weikai ZhangYa ZhangMarian L&ouml;bleret alDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 535-546 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Weikai Zhang Ya Zhang Marian L&ouml;bler et al Nuclear entry of hyperbranched polylysine nanoparticles into cochlear cells
description	Weikai Zhang1, Ya Zhang1, Marian L&ouml;bler2, Klaus-Peter Schmitz2, Aqeel Ahmad3, Ilmari Pyykk&ouml;1, Jing Zou11Department of Otolaryngology, University of Tampere, Medical School, Tampere, Finland; 2University of Rostock, Institute for Biomedical Engineering, Rostock, Germany; 3Department of Biomedical Engineering and Computational Science, Aalto University, Espoo, FinlandBackground: Gene therapy is a potentially effective therapeutic modality for treating sensorineural hearing loss. Nonviral gene delivery vectors are expected to become extremely safe and convenient, and nanoparticles are the most promising types of vectors. However, infrequent nuclear localization in the cochlear cells limits their application for gene therapy. This study aimed to investigate the potential nuclear entry of hyperbranched polylysine nanoparticles (HPNPs) for gene delivery to cochlear targets.Methods: Rat primary cochlear cells and cochlear explants generated from newborn rats were treated with different concentrations of HPNPs. For the in vivo study, HPNPs were administered to the rats&#39; round window membranes. Subcellular distribution of HPNPs in different cell populations was observed with confocal microscope 24 hours after administration.Results: Nuclear entry was observed in various cochlear cell types in vitro and in vivo. In the primary cochlear cell culture, concentration-dependent internalization was observed. In the cochlear organotypic culture, abundant HPNPs were found in the modiolus, including the spiral ganglion, organ of Corti, and lateral wall tissues. In the in vivo study, a gradient distribution of HPNPs through different layers of the round window membrane was observed. HPNPs were also distributed in the cells of the middle ear tissue. Additionally, efficient internalization of HPNPs was observed in the organ of Corti and spiral ganglion cells. In primary cochlear cells, HPNPs induced higher transfection efficiency than did LipofectamineTM.Conclusion: These results suggest that HPNPs are potentially an ideal carrier for gene delivery into the cochlea.Keywords: gene therapy, hearing loss, cochlea, internalization, nanoparticles, nuclear localization
format	article
author	Weikai Zhang Ya Zhang Marian L&ouml;bler et al
author_facet	Weikai Zhang Ya Zhang Marian L&ouml;bler et al
author_sort	Weikai Zhang
title	Nuclear entry of hyperbranched polylysine nanoparticles into cochlear cells
title_short	Nuclear entry of hyperbranched polylysine nanoparticles into cochlear cells
title_full	Nuclear entry of hyperbranched polylysine nanoparticles into cochlear cells
title_fullStr	Nuclear entry of hyperbranched polylysine nanoparticles into cochlear cells
title_full_unstemmed	Nuclear entry of hyperbranched polylysine nanoparticles into cochlear cells
title_sort	nuclear entry of hyperbranched polylysine nanoparticles into cochlear cells
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/a4e277944d16466394501365354c0ad5
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Nuclear entry of hyperbranched polylysine nanoparticles into cochlear cells

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