Hypoxia-responsive ionizable liposome delivery siRNA for glioma therapy

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, X...

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Autores principales:	Liu HM, Zhang YF, Xie YD, Cai YF, Li BY, Li W, Zeng LY, Li YL, Yu RT
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	hypoxia-responsive cellular uptake siRNA delivery ionizable liposome hypoxic conditions Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8bfcbe31f31f4a44b0fc95b19b7d0e9d
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spelling	oai:doaj.org-article:8bfcbe31f31f4a44b0fc95b19b7d0e9d2021-12-02T00:39:21ZHypoxia-responsive ionizable liposome delivery siRNA for glioma therapy1178-2013https://doaj.org/article/8bfcbe31f31f4a44b0fc95b19b7d0e9d2017-02-01T00:00:00Zhttps://www.dovepress.com/hypoxia-responsive-ionizable-liposome-delivery-sirna-for-glioma-therap-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Hong-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 conditionsLiu HMZhang YFXie YDCai YFLi BYLi WZeng LYLi YLYu RTDove Medical Pressarticlehypoxia-responsivecellular uptakesiRNA deliveryionizable liposomehypoxic conditionsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 1065-1083 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	hypoxia-responsive cellular uptake siRNA delivery ionizable liposome hypoxic conditions Medicine (General) R5-920
spellingShingle	hypoxia-responsive cellular uptake siRNA delivery ionizable liposome hypoxic conditions Medicine (General) R5-920 Liu HM Zhang YF Xie YD Cai YF Li BY Li W Zeng LY Li YL Yu RT Hypoxia-responsive ionizable liposome delivery siRNA for glioma therapy
description	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
format	article
author	Liu HM Zhang YF Xie YD Cai YF Li BY Li W Zeng LY Li YL Yu RT
author_facet	Liu HM Zhang YF Xie YD Cai YF Li BY Li W Zeng LY Li YL Yu RT
author_sort	Liu HM
title	Hypoxia-responsive ionizable liposome delivery siRNA for glioma therapy
title_short	Hypoxia-responsive ionizable liposome delivery siRNA for glioma therapy
title_full	Hypoxia-responsive ionizable liposome delivery siRNA for glioma therapy
title_fullStr	Hypoxia-responsive ionizable liposome delivery siRNA for glioma therapy
title_full_unstemmed	Hypoxia-responsive ionizable liposome delivery siRNA for glioma therapy
title_sort	hypoxia-responsive ionizable liposome delivery sirna for glioma therapy
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/8bfcbe31f31f4a44b0fc95b19b7d0e9d
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Hypoxia-responsive ionizable liposome delivery siRNA for glioma therapy

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