Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic

Songhie An,* Kihoon Nam,* Sunghyun Choi, Cheng Z Bai, Yan Lee, Jong-Sang ParkDepartment of Chemistry, Seoul National University, Seoul, Republic of Korea*These authors contributed equally to this workBackground: Glioma is still one of the most complicated forms of brain tumor to remove completely du...

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Autores principales:	An S, Nam K, Choi S, Bai CZ, Lee Y, Park JS
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2e42b4347afa45838f688e99e98815de
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spelling	oai:doaj.org-article:2e42b4347afa45838f688e99e98815de2021-12-02T02:42:08ZNonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic1176-91141178-2013https://doaj.org/article/2e42b4347afa45838f688e99e98815de2013-02-01T00:00:00Zhttp://www.dovepress.com/nonviral-gene-therapy-in-vivo-with-pam-rg4apoptin-as-a-potential-brain-a12293https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Songhie An,* Kihoon Nam,* Sunghyun Choi, Cheng Z Bai, Yan Lee, Jong-Sang ParkDepartment of Chemistry, Seoul National University, Seoul, Republic of Korea*These authors contributed equally to this workBackground: Glioma is still one of the most complicated forms of brain tumor to remove completely due to its location and the lack of an efficient means to specifically eliminate tumor cells. For these reasons, this study has examined the effectiveness of a nonviral gene therapy approach utilizing a tumor-selective killer gene on a brain tumor xenograft model.Methods and results: The therapeutic apoptin gene was recombined into the JDK plasmid and delivered into human brain tumor cells (U87MG) by using a polyamidoamine dendrimer with an arginine surface (PAM-RG4). Studies in vitro showed that the PAM-RG4/apoptin plasmid polyplex exhibited a particularly high transfection activity of &gt;40%. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, 4&acute;,6-Diamidino-2-phenylindole (DAPI) TUNEL assay, DAPI staining, and caspase-3 activity assay verified that the tumor cells had undergone apoptosis induced by apoptin. For in vivo studies, the polyplex was injected into tumors, which were induced by injecting U87MG cells intradermally into nude mice. Based on hematoxylin and eosin staining, epidermal growth factor receptor immunohistochemistry results and tumor volume measurement results, tumor growth was effectively inhibited and no specific edema, irritation, or other harm to the skin was observed after polyplex injection. The in vivo expression of apoptin and the induction of apoptosis were verified by reverse-transcription polymerase chain reaction analysis, TUNEL assay, and DAPI staining.Conclusion: The PAM-RG4/apoptin gene polyplex is a strong candidate for brain tumor therapeutics because of the synergistic effect of the carrier&#39;s high transfection efficiency (35%&ndash;40%) in glioma cells and the selective apoptosis-inducing activity of apoptin in tumor cells.Keywords: apoptin, PAM-RG4, malignant glioma, nonviral gene therapy, apoptosisAn SNam KChoi SBai CZLee YPark JSDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 821-834 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 An S Nam K Choi S Bai CZ Lee Y Park JS Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic
description	Songhie An,* Kihoon Nam,* Sunghyun Choi, Cheng Z Bai, Yan Lee, Jong-Sang ParkDepartment of Chemistry, Seoul National University, Seoul, Republic of Korea*These authors contributed equally to this workBackground: Glioma is still one of the most complicated forms of brain tumor to remove completely due to its location and the lack of an efficient means to specifically eliminate tumor cells. For these reasons, this study has examined the effectiveness of a nonviral gene therapy approach utilizing a tumor-selective killer gene on a brain tumor xenograft model.Methods and results: The therapeutic apoptin gene was recombined into the JDK plasmid and delivered into human brain tumor cells (U87MG) by using a polyamidoamine dendrimer with an arginine surface (PAM-RG4). Studies in vitro showed that the PAM-RG4/apoptin plasmid polyplex exhibited a particularly high transfection activity of &gt;40%. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, 4&acute;,6-Diamidino-2-phenylindole (DAPI) TUNEL assay, DAPI staining, and caspase-3 activity assay verified that the tumor cells had undergone apoptosis induced by apoptin. For in vivo studies, the polyplex was injected into tumors, which were induced by injecting U87MG cells intradermally into nude mice. Based on hematoxylin and eosin staining, epidermal growth factor receptor immunohistochemistry results and tumor volume measurement results, tumor growth was effectively inhibited and no specific edema, irritation, or other harm to the skin was observed after polyplex injection. The in vivo expression of apoptin and the induction of apoptosis were verified by reverse-transcription polymerase chain reaction analysis, TUNEL assay, and DAPI staining.Conclusion: The PAM-RG4/apoptin gene polyplex is a strong candidate for brain tumor therapeutics because of the synergistic effect of the carrier&#39;s high transfection efficiency (35%&ndash;40%) in glioma cells and the selective apoptosis-inducing activity of apoptin in tumor cells.Keywords: apoptin, PAM-RG4, malignant glioma, nonviral gene therapy, apoptosis
format	article
author	An S Nam K Choi S Bai CZ Lee Y Park JS
author_facet	An S Nam K Choi S Bai CZ Lee Y Park JS
author_sort	An S
title	Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic
title_short	Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic
title_full	Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic
title_fullStr	Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic
title_full_unstemmed	Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic
title_sort	nonviral gene therapy in vivo with pam-rg4/apoptin as a potential brain tumor therapeutic
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/2e42b4347afa45838f688e99e98815de
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Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic

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