title: A20 silencing by lipid envelope-type nanoparticles enhances the efficiency of lipopolysaccharide-activated dendritic cells.
abstract: In a previous report, we described the development of lipid envelope-type nanoparticles (MEND) modified with octaarginine (R8) and a pH-sensitive fusogenic peptide (GALA) for delivering short interference RNA (siRNA) to mouse dendritic cells (DCs). A20 was recently reported to be a negative regulator of the toll-like receptor and the tumor necrosis factor receptor signaling pathways. Although A20 would be expected to be a useful target for boosting the effects of adjuvants in DC immunotherapy, limited information is available regarding the use of A20-silenced DC by an original non-viral vector. In this study, we loaded anti-A20 siRNA into a MEND and investigated the gene knockdown activity in DC and the immunological functions of A20-silenced DC. The use of a MEND resulted in a significant A20 knockdown effect, and the A20-silenced DC resulted in an enhanced production of proinflammatory molecules, after lipopolysaccharide (LPS) stimulation. The expression of co-stimulatory molecules by LPS stimulation was also increased in the A20-silenced DC. The findings reported herein show that a MEND loaded with anti-A20 siRNA is a potent non-viral vector that has the ability to enhance the adjuvant effect of LPS in DC.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Warashina
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004337:Drug Carriers; D005260:Female; D055785:Gene Knockdown Techniques / Q000379:methods; D018836:Inflammation Mediators / Q000378:metabolism*; D008055:Lipids / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D034622:RNA Interference / Q000276:immunology*; D034741:RNA, Small Interfering / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D018836:Inflammation Mediators; D008055:Lipids; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering