title: Efficient delivery of therapeutic small nucleic acids to prostate cancer cells using ketal nucleoside lipid nanoparticles.
abstract: A novel nucleoside lipid derived from dioleyl ketal was synthesized from uridine in three steps starting from dioleyl ketone. Electronic microscopy studies show that Ketals Nucleoside Lipids (KNL) self-assemble to form liposome-like structures in aqueous solutions. KNL is able to bind siRNA as demonstrated by electrophoresis experiment and standard ethidium bromide fluorescence displacement assay. Transfection assays of stable hepatic cell lines HupIRF, carrying a luciferase reporter gene demonstrate that KNL is able to transfect siRNA and exhibits protein knockdown more efficiently than its diester analog (DOTAU) and lipofectamine. Herein, we also report that KNLs are suitable transfecting reagents for the development of novel therapeutic approaches involving either siRNA or antisense oligonucleotide against human prostate cancer PC-3 cells resistant to chemotherapy.
authors.affiliation: INSERM, U869, ARNA laboratory, F-33000 Bordeaux, France; Aix-Marseille University, CNRS, CINaM UMR 7325, 13288 Marseille cedex 9, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Luvino
authors.forename: Salim
authors.initials: S
authors.lastname: Khiati
authors.forename: Khalid
authors.initials: K
authors.lastname: Oumzil
authors.forename: Palma
authors.initials: P
authors.lastname: Rocchi
authors.forename: Michel
authors.initials: M
authors.lastname: Camplo
authors.forename: Philippe
authors.initials: P
authors.lastname: Barthélémy
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D009705:Nucleosides / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D014162:Transfection
chemical_list: D008055:Lipids; D008081:Liposomes; D009705:Nucleosides; D034741:RNA, Small Interfering
keywords: Antisense; Drug delivery; Nucleoside lipids; Prostate cancer; siRNA