Back to Journals » International Journal of Nanomedicine » Volume 12

Hypoxia-responsive ionizable liposome delivery siRNA for glioma therapy

Authors Liu HM, Zhang YF, Xie YD, Cai YF, Li BY, Li W, Zeng LY, Li YL, Yu RT

Received 20 October 2016

Accepted for publication 4 January 2017

Published 8 February 2017 Volume 2017:12 Pages 1065—1083


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun

Hong-Mei Liu,1,2,* Ya-Fei Zhang,1,2,* Yan-Dong Xie,1,2 Yi-Fan Cai,1,2 Bai-Yang Li,1,2 Wen Li,3 Ling-Yu Zeng,4 Yu-Ling Li,4 Ru-Tong Yu1,2

1Department of Neurosurgery, Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 2Department of Neurosurgery, Institute of Nervous System Diseases, Xuzhou Medical University, 3Department of Hematology, Affiliated Hospital of Xuzhou Medical University, 4Department of Chemistry, School of Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou, Jiangsu, People’s Republic of China

*These authors contributed equally to this work

Abstract: Here, we report the hypoxia-responsive ionizable liposomes to deliver small interference RNA (siRNA) anticancer drugs, which can selectively enhance cellular uptake of the siRNA under hypoxic and low-pH conditions to cure glioma. For this purpose, malate dehydrogenase lipid molecules were synthesized, which contain nitroimidazole groups that impart hypoxia sensitivity and specificity as hydrophobic tails, and tertiary amines as hydrophilic head groups. These malate dehydrogenase molecules, together with DSPE-PEG2000 and cholesterol, were self-assembled into O'1,O1-(3-(dimethylamino)propane-1,2-diyl) 16-bis(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl) di(hexadecanedioate) liposomes (MLP) to encapsulate siRNA through electrostatic interaction. Our study showed that the MLP could deliver polo-like kinase 1 siRNA (siPLK1) into glioma cells and effectively enhance the cellular uptake of MLP/siPLK1 because of increased positive charges induced by hypoxia and low pH. Moreover, MLP/siPLK1 was shown to be very effective in inhibiting the growth of glioma cells both in vitro and in vivo. Therefore, the MLP is a promising siRNA delivery system for tumor therapy.

Keywords: hypoxia responsive, cellular uptake, siRNA delivery, ionizable liposome, hypoxic conditions

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at 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]