生物响应性季铵盐两亲物用于 DNA 和 siRNA 的脂质体递送
Bioresponsive deciduous-charge amphiphiles for liposomal delivery of DNA and siRNA.
机构信息
Laboratoire de Conception et Application de Molécules Bioactives Faculté de Pharmacie, CNRS - Université de Strasbourg, 74 route du Rhin, BP 60024, 67401, Illkirch, France.
出版信息
Pharm Res. 2013 May;30(5):1362-79. doi: 10.1007/s11095-013-0976-9. Epub 2013 Feb 1.
PURPOSE
Biolabile cationic lipids were developed for efficient intracellular delivery of DNA and siRNA.
METHODS
The compounds have been designed starting from the membrane lipid DOPC in a way they may loose their cationic charge when exposed to an acidic and/or enzymatic stimulus, such as those met during the journey of a lipoplex in biological media.
RESULTS
They demonstrated remarkable efficiency to deliver DNA in various cell lines (BHK-21, Calu-3, NCI-H292, and A549), with no significant cytotoxicity. Furthermore, two of the compounds (carbonate-based DOPC derivatives) revealed able to deliver small interfering RNA in U87Luc and A549Luc cancer cells and to mediate a selective 70-80% knockdown of the stably transfected luciferase gene.
CONCLUSIONS
The results show that the described bioresponsive cationic lipids have high DNA and siARN delivery activity which is encouraging in view of delivering a therapeutic nucleic acid to pulmonary tissues in vivo.
目的
生物可降解阳离子脂质体被开发用于高效地将 DNA 和 siRNA 递送至细胞内。
方法
这些化合物是从细胞膜脂质 DOPC 设计而来的，当它们暴露于酸性和/或酶刺激时，它们可能会失去正电荷，例如在脂质体在生物介质中的运输过程中遇到的刺激。
结果
它们在各种细胞系（BHK-21、Calu-3、NCI-H292 和 A549）中显示出了高效递送 DNA 的能力，且没有明显的细胞毒性。此外，两种化合物（基于碳酸盐的 DOPC 衍生物）能够在 U87Luc 和 A549Luc 癌细胞中递送小干扰 RNA，并介导对稳定转染的荧光素酶基因进行选择性的 70-80%敲低。
结论
这些结果表明，所描述的生物响应性阳离子脂质体具有高效的 DNA 和 siARN 递送活性，这对于在体内将治疗性核酸递送至肺部组织是令人鼓舞的。
Zotero 插件