One-step synthesis of gene carrier via gamma irradiation and its application in tumor gene therapy

Sung In Jeong,1,* Seong-Cheol Park,2,* Sun-Jeong Park,2,* Eun-Ji Kim,2 Hun Heo,2 Jong-Seok Park,1 Hui-Jeong Gwon,1 Youn-Mook Lim,1 Mi-Kyeong Jang2 1Research Division for Industry and Environment, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, 2Department...

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Autores principales:	Jeong SI, Park S, Kim E, Heo H, Park J, Gwon H, Lim Y, Jang M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Water-soluble chitosan 2-aminoethyl methacrylate Gamma irradiation Gene delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/dfd2a6def1db4ea39983c8a36b315319
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spelling	oai:doaj.org-article:dfd2a6def1db4ea39983c8a36b3153192021-12-02T03:29:11ZOne-step synthesis of gene carrier via gamma irradiation and its application in tumor gene therapy1178-2013https://doaj.org/article/dfd2a6def1db4ea39983c8a36b3153192018-01-01T00:00:00Zhttps://www.dovepress.com/one-step-synthesis-of-gene-carrier-via-gamma-irradiation-and-its-appli-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Sung In Jeong,1,* Seong-Cheol Park,2,* Sun-Jeong Park,2,* Eun-Ji Kim,2 Hun Heo,2 Jong-Seok Park,1 Hui-Jeong Gwon,1 Youn-Mook Lim,1 Mi-Kyeong Jang2 1Research Division for Industry and Environment, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, 2Department of Polymer Science and Engineering, College of Engineering, Sunchon National University, Suncheon, Korea *These authors contributed equally to this work Introduction: Although numerous studies have been conducted with the aim of developing drug-delivery systems, chemically synthesized gene carriers have shown limited applications in the biomedical fields due to several problems, such as low-grafting yields, undesirable reactions, difficulties in controlling the reactions, and high-cost production owing to multi-step manufacturing processes. Materials and methods: We developed a 1-step synthesis process to produce 2-aminoethyl methacrylate-grafted water-soluble chitosan (AEMA-g-WSC) as a gene carrier, using gamma irradiation for simultaneous synthesis and sterilization, but no catalysts or photoinitiators. We analyzed the AEMA graft site on WSC using 2-dimensional nuclear magnetic resonance spectroscopy (2D NMR; 1H and 13C NMR), and assayed gene transfection effects in vitro and in vivo. Results: We revealed selective grafting of AEMA onto C6-OH groups of WSC. AEMA-g-WSC effectively condensed plasmid DNA to form polyplexes in the size range of 170 to 282 nm. AEMA-g-WSC polyplexes in combination with psi-hBCL2 (a vector expressing short hairpin RNA against BCL2 mRNA) inhibited tumor cell proliferation and tumor growth in vitro and in vivo, respectively, by inducing apoptosis. Conclusion: The simple grafting process mediated via gamma irradiation is a promising method for synthesizing gene carriers. Keywords: water-soluble chitosan, 2-aminoethyl methacrylate, gamma irradiation, gene deliveryJeong SIPark SPark SKim EHeo HPark JGwon HLim YJang MDove Medical PressarticleWater-soluble chitosan2-aminoethyl methacrylateGamma irradiationGene deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 525-536 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Water-soluble chitosan 2-aminoethyl methacrylate Gamma irradiation Gene delivery Medicine (General) R5-920
spellingShingle	Water-soluble chitosan 2-aminoethyl methacrylate Gamma irradiation Gene delivery Medicine (General) R5-920 Jeong SI Park S Park S Kim E Heo H Park J Gwon H Lim Y Jang M One-step synthesis of gene carrier via gamma irradiation and its application in tumor gene therapy
description	Sung In Jeong,1,* Seong-Cheol Park,2,* Sun-Jeong Park,2,* Eun-Ji Kim,2 Hun Heo,2 Jong-Seok Park,1 Hui-Jeong Gwon,1 Youn-Mook Lim,1 Mi-Kyeong Jang2 1Research Division for Industry and Environment, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, 2Department of Polymer Science and Engineering, College of Engineering, Sunchon National University, Suncheon, Korea *These authors contributed equally to this work Introduction: Although numerous studies have been conducted with the aim of developing drug-delivery systems, chemically synthesized gene carriers have shown limited applications in the biomedical fields due to several problems, such as low-grafting yields, undesirable reactions, difficulties in controlling the reactions, and high-cost production owing to multi-step manufacturing processes. Materials and methods: We developed a 1-step synthesis process to produce 2-aminoethyl methacrylate-grafted water-soluble chitosan (AEMA-g-WSC) as a gene carrier, using gamma irradiation for simultaneous synthesis and sterilization, but no catalysts or photoinitiators. We analyzed the AEMA graft site on WSC using 2-dimensional nuclear magnetic resonance spectroscopy (2D NMR; 1H and 13C NMR), and assayed gene transfection effects in vitro and in vivo. Results: We revealed selective grafting of AEMA onto C6-OH groups of WSC. AEMA-g-WSC effectively condensed plasmid DNA to form polyplexes in the size range of 170 to 282 nm. AEMA-g-WSC polyplexes in combination with psi-hBCL2 (a vector expressing short hairpin RNA against BCL2 mRNA) inhibited tumor cell proliferation and tumor growth in vitro and in vivo, respectively, by inducing apoptosis. Conclusion: The simple grafting process mediated via gamma irradiation is a promising method for synthesizing gene carriers. Keywords: water-soluble chitosan, 2-aminoethyl methacrylate, gamma irradiation, gene delivery
format	article
author	Jeong SI Park S Park S Kim E Heo H Park J Gwon H Lim Y Jang M
author_facet	Jeong SI Park S Park S Kim E Heo H Park J Gwon H Lim Y Jang M
author_sort	Jeong SI
title	One-step synthesis of gene carrier via gamma irradiation and its application in tumor gene therapy
title_short	One-step synthesis of gene carrier via gamma irradiation and its application in tumor gene therapy
title_full	One-step synthesis of gene carrier via gamma irradiation and its application in tumor gene therapy
title_fullStr	One-step synthesis of gene carrier via gamma irradiation and its application in tumor gene therapy
title_full_unstemmed	One-step synthesis of gene carrier via gamma irradiation and its application in tumor gene therapy
title_sort	one-step synthesis of gene carrier via gamma irradiation and its application in tumor gene therapy
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/dfd2a6def1db4ea39983c8a36b315319
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One-step synthesis of gene carrier via gamma irradiation and its application in tumor gene therapy

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