Back to Journals » International Journal of Nanomedicine » Volume 7

Suppression of lung cancer progression by biocompatible glycerol triacrylate– spermine-mediated delivery of shAkt1

Authors Hong SH, Kim JE, Kim YK, Minai-Tehrani A, Shin JY, Kang B, Kim HJ, Cho CS, Chae C, Jiang HL, Cho MH

Received 13 December 2011

Accepted for publication 15 February 2012

Published 4 May 2012 Volume 2012:7 Pages 2293—2306

DOI https://doi.org/10.2147/IJN.S29152

Review by Single-blind

Peer reviewer comments 3

Seong-Ho Hong1,*, Ji-Eun Kim1,6,*, You-Kyoung Kim2, Arash Minai-Tehrani1, Ji-Young Shin1, Bitna Kang1, Hye-Joon Kim1, Chong-Su Cho2, Chanhee Chae3, Hu-Lin Jiang1, Myung-Haing Cho1,4–7
1Laboratory of Toxicology, 2Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, 3Laboratory of Pathology, College of Veterinary Medicine, 4Graduate Group of Tumor Biology, 5Center for Food and Toxicology, Seoul National University, Seoul, Korea; 6Department of Nano Fusion Technology, Graduate School of Convergence Science and Technology, 7Advanced Institute of Convergence Technology, Seoul National University, Suwon, Korea

*These authors contributed equally to this work

Background: Polyethylenimine (PEI)-based nonviral gene-delivery systems are commonly employed because of their high transfection efficiency. However, the toxic nature of PEI is a significant obstacle in clinical gene therapy. In this study, we developed biocompatible glycerol triacrylate–spermine (GT–SPE) polyspermine as a nanosized gene carrier for potential lung cancer gene therapy.
Methods: The GT–SPE was synthesized using the Michael addition reaction between GT and SPE. The molecular weight was characterized using gel permeability chromatography multiangle laser light scattering and the composition of the polymer was analyzed using proton nuclear magnetic resonance.
Results: The GT–SPE successfully protected the DNA from nucleases. The average particle size of the GT–SPE was 121 nm with a zeta potential of +23.45 mV. The GT–SPE was found to be less toxic than PEI for various cell lines, as well as for a murine model. Finally, our results showed that the GT–SPE/small hairpin Akt1 (shAkt1) complex suppressed lung tumorigenesis in a K-rasLA1 lung cancer mice model by inducing apoptosis through the Akt signaling pathway and cell cycle arrest. Aerosol delivered GT–SPE/shAkt1, which reduced matrix metalloproteinase-9 activity and suppressed the expression levels of proliferating cell nuclear antigen, as well as vascular endothelial growth factors and CD31, which are known proliferation and angiogenesis markers, respectively.
Conclusion: Our data suggest that GT–SPE may be a candidate for short hairpin-shaped RNA-based aerosol lung cancer gene therapy.

Keywords: lung cancer, gene therapy, aerosol delivery, spermine

Corrigendum has been published for this paper.

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Readers of this article also read:

Green synthesis of water-soluble nontoxic polymeric nanocomposites containing silver nanoparticles

Prozorova GF, Pozdnyakov AS, Kuznetsova NP, Korzhova SA, Emel’yanov AI, Ermakova TG, Fadeeva TV, Sosedova LM

International Journal of Nanomedicine 2014, 9:1883-1889

Published Date: 16 April 2014

Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

Ashwanikumar N, Kumar NA, Nair SA, Kumar GS

International Journal of Nanomedicine 2012, 7:5769-5779

Published Date: 15 November 2012

A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone

Hu Z, Liao M, Chen Y, Cai Y, Meng L, Liu Y, Lv N, Liu Z, Yuan W

International Journal of Nanomedicine 2012, 7:5719-5724

Published Date: 12 November 2012

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Servant leadership: a case study of a Canadian health care innovator

Vanderpyl TH

Journal of Healthcare Leadership 2012, 4:9-16

Published Date: 16 February 2012

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010