Bioresponsive deciduous-charge amphiphiles for liposomal delivery of DNA and siRNA.

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.