Target-specific delivery of siRNA into hepatoma cells' cytoplasm by bifunctional carrier peptide.

RNA interference (RNAi) is among the most potential approach for the therapy of hepatocellular carcinoma and the major barrier hindering siRNA therapeutics is the low efficiency of delivery to the desired cells. The current study aimed at developing a novel peptide for more efficient hepatoma targeted siRNA delivery, by combining luteinizing hormone-releasing hormone with hepatoma targeting specificity and MPG△NLS with cytoplasm-delivery tendency. The developed bifunctional peptide LHRH-MPG△NLS and siRNA were mixed together and resulted in LHRH-MPG△NLS/siRNA polyplexes through self-assembly. The polyplexes were characterized by agarose gel retardation and dynamic light scatting analysis. Hepatoma targeting specificity was analyzed with the GE IN Cell Analyzer 2000 High-Content Cellular Analysis System after cell transfection, and the effect of RNA interference was detected by RT-PCR. The results demonstrated that LHRH-MPG△NLS was able to assemble with siRNA to form stable and nano-sized peptide/siRNA polyplexes, which could inhibit the expression of the target gene and was essentially non-cytotoxic, as compared with the commercial transfection reagent lipofectamine 2000.