Delivery system for DNAzymes using arginine-modified hydroxyapatite nanoparticles for therapeutic application in a nasopharyngeal carcinoma model

Yan Chen,1 Lifang Yang,1,2 Suping Huang,3 Zhi Li,1 Lu Zhang,1 Jiang He,1 Zhijie Xu,2 Liyu Liu,2 Ya Cao,2 Lunquan Sun11Center for Molecular Medicine, Xiangya Hospital, 2Cancer Research Institute, 3State Key Laboratory of Powder Metallurgy, Central South University, Changsha, People's Republic...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Chen Y, Yang LF, Huang SP, Li Z, Zhang L, He J, Xu ZJ, Liu LY, Cao Y, Sun LQ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c83b4fc5174041d18380dc64c028a971
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c83b4fc5174041d18380dc64c028a971
record_format	dspace
spelling	oai:doaj.org-article:c83b4fc5174041d18380dc64c028a9712021-12-02T02:42:32ZDelivery system for DNAzymes using arginine-modified hydroxyapatite nanoparticles for therapeutic application in a nasopharyngeal carcinoma model1176-91141178-2013https://doaj.org/article/c83b4fc5174041d18380dc64c028a9712013-08-01T00:00:00Zhttp://www.dovepress.com/delivery-system-for-dnazymes-using-arginine-modified-hydroxyapatite-na-a14037https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Yan Chen,1 Lifang Yang,1,2 Suping Huang,3 Zhi Li,1 Lu Zhang,1 Jiang He,1 Zhijie Xu,2 Liyu Liu,2 Ya Cao,2 Lunquan Sun11Center for Molecular Medicine, Xiangya Hospital, 2Cancer Research Institute, 3State Key Laboratory of Powder Metallurgy, Central South University, Changsha, People's Republic of ChinaAbstract: DNAzymes are synthetic, single-stranded, catalytic nucleic acids that bind and cleave target mRNA in a sequence-specific manner, and have been explored for genotherapeutics. One bottleneck restricting their application is the lack of an efficient delivery system. As an inorganic nanomaterial with potentially wide application, nanohydroxyapatite particles (nHAP) have attracted increasing attention as new candidates for nonviral vectors. In this study, we developed an nHAP-based delivery system and explored its cellular uptake mechanisms, intracellular localization, and biological effects. Absorption of arginine-modified nanohydroxyapatite particles (Arg-nHAP) and DZ1 (latent membrane protein 1 [LMP1]-targeted) reached nearly 100% efficiency under in vitro conditions. Using specific inhibitors, cellular uptake of the Arg-nHAP/DZ1 complex was shown to be mediated by the energy-dependent endocytosis pathway. Further, effective intracellular delivery and nuclear localization of the complex was confirmed by confocal microscopy. Biologically, the complex successfully downregulated the expression of LMP1 in nasopharyngeal carcinoma cells. In a mouse tumor xenograft model, the complex was shown to be delivered efficiently to tumor tissue, downregulating expression of LMP1 and suppressing tumor growth. These results suggest that Arg-nHAP may be an efficient vector for nucleic acid-based drugs with potential clinical application.Keywords: hydroxyapatite nanoparticles, DNAzymes, latent membrane protein 1, transfection efficiency, cellular uptakeChen YYang LFHuang SPLi ZZhang LHe JXu ZJLiu LYCao YSun LQDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 3107-3118 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Chen Y Yang LF Huang SP Li Z Zhang L He J Xu ZJ Liu LY Cao Y Sun LQ Delivery system for DNAzymes using arginine-modified hydroxyapatite nanoparticles for therapeutic application in a nasopharyngeal carcinoma model
description	Yan Chen,1 Lifang Yang,1,2 Suping Huang,3 Zhi Li,1 Lu Zhang,1 Jiang He,1 Zhijie Xu,2 Liyu Liu,2 Ya Cao,2 Lunquan Sun11Center for Molecular Medicine, Xiangya Hospital, 2Cancer Research Institute, 3State Key Laboratory of Powder Metallurgy, Central South University, Changsha, People's Republic of ChinaAbstract: DNAzymes are synthetic, single-stranded, catalytic nucleic acids that bind and cleave target mRNA in a sequence-specific manner, and have been explored for genotherapeutics. One bottleneck restricting their application is the lack of an efficient delivery system. As an inorganic nanomaterial with potentially wide application, nanohydroxyapatite particles (nHAP) have attracted increasing attention as new candidates for nonviral vectors. In this study, we developed an nHAP-based delivery system and explored its cellular uptake mechanisms, intracellular localization, and biological effects. Absorption of arginine-modified nanohydroxyapatite particles (Arg-nHAP) and DZ1 (latent membrane protein 1 [LMP1]-targeted) reached nearly 100% efficiency under in vitro conditions. Using specific inhibitors, cellular uptake of the Arg-nHAP/DZ1 complex was shown to be mediated by the energy-dependent endocytosis pathway. Further, effective intracellular delivery and nuclear localization of the complex was confirmed by confocal microscopy. Biologically, the complex successfully downregulated the expression of LMP1 in nasopharyngeal carcinoma cells. In a mouse tumor xenograft model, the complex was shown to be delivered efficiently to tumor tissue, downregulating expression of LMP1 and suppressing tumor growth. These results suggest that Arg-nHAP may be an efficient vector for nucleic acid-based drugs with potential clinical application.Keywords: hydroxyapatite nanoparticles, DNAzymes, latent membrane protein 1, transfection efficiency, cellular uptake
format	article
author	Chen Y Yang LF Huang SP Li Z Zhang L He J Xu ZJ Liu LY Cao Y Sun LQ
author_facet	Chen Y Yang LF Huang SP Li Z Zhang L He J Xu ZJ Liu LY Cao Y Sun LQ
author_sort	Chen Y
title	Delivery system for DNAzymes using arginine-modified hydroxyapatite nanoparticles for therapeutic application in a nasopharyngeal carcinoma model
title_short	Delivery system for DNAzymes using arginine-modified hydroxyapatite nanoparticles for therapeutic application in a nasopharyngeal carcinoma model
title_full	Delivery system for DNAzymes using arginine-modified hydroxyapatite nanoparticles for therapeutic application in a nasopharyngeal carcinoma model
title_fullStr	Delivery system for DNAzymes using arginine-modified hydroxyapatite nanoparticles for therapeutic application in a nasopharyngeal carcinoma model
title_full_unstemmed	Delivery system for DNAzymes using arginine-modified hydroxyapatite nanoparticles for therapeutic application in a nasopharyngeal carcinoma model
title_sort	delivery system for dnazymes using arginine-modified hydroxyapatite nanoparticles for therapeutic application in a nasopharyngeal carcinoma model
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/c83b4fc5174041d18380dc64c028a971
work_keys_str_mv	AT cheny deliverysystemfordnazymesusingargininemodifiedhydroxyapatitenanoparticlesfortherapeuticapplicationinanasopharyngealcarcinomamodel AT yanglf deliverysystemfordnazymesusingargininemodifiedhydroxyapatitenanoparticlesfortherapeuticapplicationinanasopharyngealcarcinomamodel AT huangsp deliverysystemfordnazymesusingargininemodifiedhydroxyapatitenanoparticlesfortherapeuticapplicationinanasopharyngealcarcinomamodel AT liz deliverysystemfordnazymesusingargininemodifiedhydroxyapatitenanoparticlesfortherapeuticapplicationinanasopharyngealcarcinomamodel AT zhangl deliverysystemfordnazymesusingargininemodifiedhydroxyapatitenanoparticlesfortherapeuticapplicationinanasopharyngealcarcinomamodel AT hej deliverysystemfordnazymesusingargininemodifiedhydroxyapatitenanoparticlesfortherapeuticapplicationinanasopharyngealcarcinomamodel AT xuzj deliverysystemfordnazymesusingargininemodifiedhydroxyapatitenanoparticlesfortherapeuticapplicationinanasopharyngealcarcinomamodel AT liuly deliverysystemfordnazymesusingargininemodifiedhydroxyapatitenanoparticlesfortherapeuticapplicationinanasopharyngealcarcinomamodel AT caoy deliverysystemfordnazymesusingargininemodifiedhydroxyapatitenanoparticlesfortherapeuticapplicationinanasopharyngealcarcinomamodel AT sunlq deliverysystemfordnazymesusingargininemodifiedhydroxyapatitenanoparticlesfortherapeuticapplicationinanasopharyngealcarcinomamodel
_version_	1718402249816801280

Delivery system for DNAzymes using arginine-modified hydroxyapatite nanoparticles for therapeutic application in a nasopharyngeal carcinoma model

Ejemplares similares