title: Improved siRNA delivery efficiency via solvent-induced condensation of micellar nanoparticles.
abstract: Efficient delivery of short interfering RNA (siRNA) remains one of the primary challenges of RNA interference therapy. Polyethylene glycol (PEG)ylated polycationic carriers have been widely used for the condensation of DNA and RNA molecules into complex-core micelles. The PEG corona of such nanoparticles can significantly improve their colloidal stability in serum, but PEGylation of the carriers also reduces their condensation capacity, hindering the generation of micellar particles with sufficient complex stability. This presents a particularly significant challenge for packaging siRNA into complex micelles, as it has a much smaller size and more rigid chain structure than DNA plasmids. Here, we report a new method to enhance the condensation of siRNA with PEGylated linear polyethylenimine using organic solvent and to prepare smaller siRNA nanoparticles with a more extended PEG corona and consequently higher stability. As a proof of principle, we have demonstrated the improved gene knockdown efficiency resulting from the reduced siRNA micelle size in mice livers following intravenous administration.
authors.affiliation: Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, United States of America.
authors.forename: Juan
authors.initials: J
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.forename: John-Michael
authors.initials: JM
authors.lastname: Williford
authors.forename: Yong
authors.initials: Y
authors.lastname: Ren
authors.forename: Xuesong
authors.initials: X
authors.lastname: Jiang
authors.forename: Xuan
authors.initials: X
authors.lastname: Jiang
authors.forename: Deng
authors.initials: D
authors.lastname: Pan
authors.forename: Hai-Quan
authors.initials: HQ
authors.lastname: Mao
authors.forename: Erik
authors.initials: E
authors.lastname: Luijten
mesh_terms: D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D012997:Solvents / Q000737:chemistry*
chemical_list: D008823:Micelles; D034741:RNA, Small Interfering; D012997:Solvents; D011092:Polyethylene Glycols; D011094:Polyethyleneimine