Enhanced siRNA Delivery Using Oleic Acid Derivative of Polyethylenimine

Background: RNA interference has promising therapeutic potential. However, safe and efficacious delivery systems are necessary for its application in the clinic. Materials and Methods: An oleic acid (OA) derivative of branched polyethylenimine (PEI, M.W. 2000 Da), PEI-OA, was synthesized and evaluated for small interfering RNA (siRNA) delivery in SK-HEP-1 liver cancer cells stably transfected with luciferase. The physiochemical properties of PEI-OA/siRNA complexes, their cellular uptake, gene silencing activity based on luciferase reporter gene down-regulation, and cytotoxicity were investigated. Results: PEI-OA complexes effectively delivered siRNA into SK-HEP-1 cells and efficiently induced down-regulation of luciferase reporter gene expression. Compared with free siRNA and PEI/siRNA, PEI-OA/siRNA was significantly more effective, reducing luciferase activity by similar to 50%. Conclusion.: PEI-OA warrants further evaluation for therapeutic delivery of siRNA.