Tat peptide-decorated gelatin-siloxane nanoparticles for delivery of CGRP transgene in treatment of cerebral vasospasm

Xin-Hua Tian,1,2 Zhi-Gang Wang,1,2 Han Meng,1,2 Yu-Hua Wang,2 Wei Feng,2 Feng Wei,2 Zhi-Chun Huang,2 Xiao-Ning Lin,2 Lei Ren3,41Xiehe Clinical College of Medicine, Fujian Medical University, Fuzhou, 2Department of Neurosurgery, Zhongshan Hospital, 3Research Center of Biomedical Engineering, Departme...

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Autores principales:	Tian XH, Wang ZG, Meng H, Wang YH, Feng W, Wei F, Huang ZC, Lin XN, Ren L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5b6509eb58a241d283c69f364bfe091f
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spelling	oai:doaj.org-article:5b6509eb58a241d283c69f364bfe091f2021-12-02T05:04:30ZTat peptide-decorated gelatin-siloxane nanoparticles for delivery of CGRP transgene in treatment of cerebral vasospasm1176-91141178-2013https://doaj.org/article/5b6509eb58a241d283c69f364bfe091f2013-03-01T00:00:00Zhttp://www.dovepress.com/tat-peptide-decorated-gelatin-siloxane-nanoparticles-for-delivery-of-c-a12586https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Xin-Hua Tian,1,2 Zhi-Gang Wang,1,2 Han Meng,1,2 Yu-Hua Wang,2 Wei Feng,2 Feng Wei,2 Zhi-Chun Huang,2 Xiao-Ning Lin,2 Lei Ren3,41Xiehe Clinical College of Medicine, Fujian Medical University, Fuzhou, 2Department of Neurosurgery, Zhongshan Hospital, 3Research Center of Biomedical Engineering, Department of Biomaterials, College of Materials, 4State Key Laboratory for Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen, People's Republic of ChinaBackground: Gene transfer using a nanoparticle vector is a promising new approach for the safe delivery of therapeutic genes in human disease. The Tat peptide-decorated gelatin-siloxane (Tat-GS) nanoparticle has been demonstrated to be biocompatible as a vector, and to have enhanced gene transfection efficiency compared with the commercial reagent. This study investigated whether intracisternal administration of Tat-GS nanoparticles carrying the calcitonin gene-related peptide (CGRP) gene can attenuate cerebral vasospasm and improve neurological outcomes in a rat model of subarachnoid hemorrhage.Method: A series of gelatin-siloxane nanoparticles with controlled size and surface charge was synthesized by a two-step sol-gel process, and then modified with the Tat peptide. The efficiency of Tat-GS nanoparticle-mediated gene transfer of pLXSN-CGRP was investigated in vitro using brain capillary endothelial cells and in vivo using a double-hemorrhage rat model. For in vivo analysis, we delivered Tat-GS nanoparticles encapsulating pLXSN-CGRP intracisternally using a double-hemorrhage rat model.Results: In vitro, Tat-GS nanoparticles encapsulating pLXSN-CGRP showed 1.71 times higher sustained CGRP expression in endothelial cells than gelatin-siloxane nanoparticles encapsulating pLXSN-CGRP, and 6.92 times higher CGRP expression than naked pLXSN-CGRP. However, there were no significant differences in pLXSN-CGRP entrapment efficiency and cellular uptake between the Tat-GS nanoparticles and gelatin-siloxane nanoparticles. On day 7 of the in vivo experiment, the data indicated better neurological outcomes and reduced vasospasm in the subarachnoid hemorrhage group that received Tat-GS nanoparticles encapsulating pLXSN-CGRP than in the group receiving Tat-GS nanoparticles encapsulating pLXSN alone because of enhanced vasodilatory CGRP expression in cerebrospinal fluid.Conclusion: Overexpression of CGRP attenuated vasospasm and improved neurological outcomes in an experimental rat model of subarachnoid hemorrhage. Tat-GS nanoparticle-mediated CGRP gene delivery could be an innovative strategy for treatment of cerebral vasospasm after subarachnoid hemorrhage.Keywords: gene transfer, nanoparticles, calcitonin gene-related peptide, cerebral vasospasmTian XHWang ZGMeng HWang YHFeng WWei FHuang ZCLin XNRen LDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 865-876 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Tian XH Wang ZG Meng H Wang YH Feng W Wei F Huang ZC Lin XN Ren L Tat peptide-decorated gelatin-siloxane nanoparticles for delivery of CGRP transgene in treatment of cerebral vasospasm
description	Xin-Hua Tian,1,2 Zhi-Gang Wang,1,2 Han Meng,1,2 Yu-Hua Wang,2 Wei Feng,2 Feng Wei,2 Zhi-Chun Huang,2 Xiao-Ning Lin,2 Lei Ren3,41Xiehe Clinical College of Medicine, Fujian Medical University, Fuzhou, 2Department of Neurosurgery, Zhongshan Hospital, 3Research Center of Biomedical Engineering, Department of Biomaterials, College of Materials, 4State Key Laboratory for Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen, People's Republic of ChinaBackground: Gene transfer using a nanoparticle vector is a promising new approach for the safe delivery of therapeutic genes in human disease. The Tat peptide-decorated gelatin-siloxane (Tat-GS) nanoparticle has been demonstrated to be biocompatible as a vector, and to have enhanced gene transfection efficiency compared with the commercial reagent. This study investigated whether intracisternal administration of Tat-GS nanoparticles carrying the calcitonin gene-related peptide (CGRP) gene can attenuate cerebral vasospasm and improve neurological outcomes in a rat model of subarachnoid hemorrhage.Method: A series of gelatin-siloxane nanoparticles with controlled size and surface charge was synthesized by a two-step sol-gel process, and then modified with the Tat peptide. The efficiency of Tat-GS nanoparticle-mediated gene transfer of pLXSN-CGRP was investigated in vitro using brain capillary endothelial cells and in vivo using a double-hemorrhage rat model. For in vivo analysis, we delivered Tat-GS nanoparticles encapsulating pLXSN-CGRP intracisternally using a double-hemorrhage rat model.Results: In vitro, Tat-GS nanoparticles encapsulating pLXSN-CGRP showed 1.71 times higher sustained CGRP expression in endothelial cells than gelatin-siloxane nanoparticles encapsulating pLXSN-CGRP, and 6.92 times higher CGRP expression than naked pLXSN-CGRP. However, there were no significant differences in pLXSN-CGRP entrapment efficiency and cellular uptake between the Tat-GS nanoparticles and gelatin-siloxane nanoparticles. On day 7 of the in vivo experiment, the data indicated better neurological outcomes and reduced vasospasm in the subarachnoid hemorrhage group that received Tat-GS nanoparticles encapsulating pLXSN-CGRP than in the group receiving Tat-GS nanoparticles encapsulating pLXSN alone because of enhanced vasodilatory CGRP expression in cerebrospinal fluid.Conclusion: Overexpression of CGRP attenuated vasospasm and improved neurological outcomes in an experimental rat model of subarachnoid hemorrhage. Tat-GS nanoparticle-mediated CGRP gene delivery could be an innovative strategy for treatment of cerebral vasospasm after subarachnoid hemorrhage.Keywords: gene transfer, nanoparticles, calcitonin gene-related peptide, cerebral vasospasm
format	article
author	Tian XH Wang ZG Meng H Wang YH Feng W Wei F Huang ZC Lin XN Ren L
author_facet	Tian XH Wang ZG Meng H Wang YH Feng W Wei F Huang ZC Lin XN Ren L
author_sort	Tian XH
title	Tat peptide-decorated gelatin-siloxane nanoparticles for delivery of CGRP transgene in treatment of cerebral vasospasm
title_short	Tat peptide-decorated gelatin-siloxane nanoparticles for delivery of CGRP transgene in treatment of cerebral vasospasm
title_full	Tat peptide-decorated gelatin-siloxane nanoparticles for delivery of CGRP transgene in treatment of cerebral vasospasm
title_fullStr	Tat peptide-decorated gelatin-siloxane nanoparticles for delivery of CGRP transgene in treatment of cerebral vasospasm
title_full_unstemmed	Tat peptide-decorated gelatin-siloxane nanoparticles for delivery of CGRP transgene in treatment of cerebral vasospasm
title_sort	tat peptide-decorated gelatin-siloxane nanoparticles for delivery of cgrp transgene in treatment of cerebral vasospasm
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/5b6509eb58a241d283c69f364bfe091f
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Tat peptide-decorated gelatin-siloxane nanoparticles for delivery of CGRP transgene in treatment of cerebral vasospasm

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