title: Enhanced hepatic delivery of siRNA and microRNA using oleic acid based lipid nanoparticle formulations.
abstract: Many cationic lipids have been developed for lipid-based nanoparticles (LNPs) for delivery of siRNA and microRNA (miRNA). However, less attention has been paid to "helper lipids". Here, we investigated several "helper lipids" and examined their effects on the physicochemical properties such as particle size and zeta potential, as well as cellular uptake and transfection efficiency. We found that inclusion of oleic acid (OA), an unsaturated fatty acid, into the LNP formulation significantly enhanced the delivery efficacy for siRNA and miRNA. For proof-of-concept, miR-122, a liver-specific microRNA associated with many liver diseases, was used as a model agent to demonstrate the hepatic delivery efficacy both in tumor cells and in animals. Compared to Lipofectamine 2000, a commercial transfection agent, LNPs containing OA delivered microRNA-122 in a more efficient manner with a 1.8-fold increase in mature miR-122 expression and a 20% decrease in Bcl-w, a target of microRNA-122. In comparison with Invivofectamine, a commercial transfection agent specifically designed for hepatic delivery, LNPs containing OA showed comparable liver accumulation and in vivo delivery efficiency. These findings demonstrated the importance of "helper lipid" components of the LNP formulation on the cellular uptake and transfection activity of siRNA and miRNA. LNPs containing OA is a promising nanocarrier system for the delivery of RNA-based therapeutics in liver diseases.
authors.affiliation: NSF Nanoscale Science and Engineering Center (NSEC), The Ohio State University, Columbus, USA.
authors.forename: Xinmei
authors.initials: X
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Ren
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Mo
authors.forename: Chenguang
authors.initials: C
authors.lastname: Zhou
authors.forename: Hongyan
authors.initials: H
authors.lastname: He
authors.forename: Huliang
authors.initials: H
authors.lastname: Jia
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Samson T
authors.initials: ST
authors.lastname: Jacob
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.forename: Kalpana
authors.initials: K
authors.lastname: Ghoshal
authors.forename: L James
authors.initials: LJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D002460:Cell Line; D056945:Hep G2 Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D019301:Oleic Acid / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014162:Transfection
chemical_list: D008055:Lipids; C086724:Lipofectamine; D034741:RNA, Small Interfering; D019301:Oleic Acid
keywords: Cationic lipid nanoparticles; Helper lipids; Hepatic delivery; microRNA; siRNA