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

Authors Jeong SI, Park S, Park S, Kim E, Heo H, Park J, Gwon H, Lim Y, Jang M

Received 19 August 2017

Accepted for publication 9 December 2017

Published 25 January 2018 Volume 2018:13 Pages 525—536

DOI https://doi.org/10.2147/IJN.S149532

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Jia Fan

Peer reviewer comments 3

Editor who approved publication: Dr Thomas Webster


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

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