期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 12, 期 -, 页码 1065-1083出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S125286
关键词
hypoxia responsive; cellular uptake; siRNA delivery; ionizable liposome; hypoxic conditions
资金
- National Natural Science Foundation of China [81272777, 81502153, 81472345]
- Natural Science Foundation of Jiangsu Province [BK20150221]
- China Postdoctoral Science Foundation [2016M591926]
- Key Research & Development Plan of Jiangsu Province [BE2016646]
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), O-1-(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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据