Synthesis Of Novel Cholesterol-based Lipoplexes For Gene Delivery

RNA interference(RNAi)has shown great potential for clinical treatment of a variety of diseases.It is a highly efficient approach for gene silencing.Regulation of gene expression at posttranscriptional level is an effective method for treatment of various diseases.However,due to the lack of highly efficient and highly biocompatible delivery carrier,the clinical application of RNAi has been seriously hindered.Therefore,developing a safe and targeted delivery system is an urgent problem to be solved.Here we report the synthesis of highly efficient cholesterol-based lipoplexes for gene/plasmid delivery agent based on a few novel peptides built from cholesterol and natural amino acids.Fine tuning of the composition of amino acids,the type of amide linkage in the peptides,as well as the formulation and the physicochemical parameters of the novel lipoplex resulted in a lipid nanoparticle(LNP)that efficiently delivers plasmid to several cancer cell lines(HeLa cells,293T cells and HepG2 cells).Plasmid delivery experiments showed that the cholesterol-based lipoplex was highly efficient for plasmid(GFP)delivery in various cell lines.Compared to Lipofectamine 2000,the lipoplex showed high efficiency and apparently less cytotoxicity.