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Hypoxia-responsive ionizable liposome delivery siRNA for glioma therapy.


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.

SUBMITTER: Liu HM 

PROVIDER: S-EPMC5308568 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Hypoxia-responsive ionizable liposome delivery siRNA for glioma therapy.

Liu Hong-Mei HM   Zhang Ya-Fei YF   Xie Yan-Dong YD   Cai Yi-Fan YF   Li Bai-Yang BY   Li Wen W   Zeng Ling-Yu LY   Li Yu-Ling YL   Yu Ru-Tong RT  

International journal of nanomedicine 20170208


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, toget  ...[more]

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