title: Synthesis and properties of vitamin E analog-conjugated neomycin for delivery of RNAi drugs to liver cells.
abstract: RNA interference (RNAi) is a promising tool to regulate gene expression by external double stranded RNAs (dsRNAs) such as siRNAs. As an efficient method to deliver siRNAs to liver cells, we propose a novel strategy using vitamin E (VE)-conjugated neomycin derivatives. With the aim of delivering RNAi-based drugs to liver cells, several tripod-type and prodrug-type neomycin derivatives were synthesized, all of which were thermodynamically stabilized RNA duplexes. The prodrug-type derivative 7 and the tripod-type derivative 10 were delivered to liver cancer cells and successfully induced RNAi activity. These results indicated the potential use of natural aminoglycosides as carriers of RNAi drugs.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Japan; JST-CREST, K's Gobancho 6F, 7, Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan.
authors.forename: Rintaro
authors.initials: R
authors.lastname: Iwata
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Bioscience Building 702, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Nakayama
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Bioscience Building 702, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan.
authors.forename: Sakie
authors.initials: S
authors.lastname: Hirochi
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Bioscience Building 702, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sato
authors.affiliation: JST-CREST, K's Gobancho 6F, 7, Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan; Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Wenying
authors.initials: W
authors.lastname: Piao
authors.affiliation: JST-CREST, K's Gobancho 6F, 7, Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan; Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Nishina
authors.affiliation: JST-CREST, K's Gobancho 6F, 7, Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan; Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Yokota
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Japan; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Bioscience Building 702, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan; JST-CREST, K's Gobancho 6F, 7, Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan. Electronic address: twada@rs.tus.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Wada
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D009355:Neomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000008:administration & dosage / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D014810:Vitamin E; D009355:Neomycin
keywords: Drug delivery system; Neomycin B; RNA interference; Vitamin E