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.