title: Reductively Cleavable Nanocaplets for siRNA Delivery by Template-Assisted Oxidative Polymerization.
abstract: A series of water-soluble telechelic dithiol monomers bearing multiple guanidinium ion (Gu(+)) units in their main chains were synthesized for packaging siRNA by template-assisted oxidative polymerization at their thiol termini. In the presence of siRNA, oxidative polymerization of (TEG)Gu4 affords a uniform-sized (7 ± 2 nm) nanocaplet containing siRNA (P(TEG)Gu4⊃siRNA; P(TEG)Gu4 = polymerized (TEG)Gu4). When this small conjugate is incubated with live cells, cellular uptake occurs, and the nanocaplet undergoes depolymerization in the reductive cytosolic environment to liberate the packaged siRNA. Consequently, gene expression in the live cells is suppressed.
authors.affiliation: Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: P K
authors.initials: PK
authors.lastname: Hashim
authors.affiliation: Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Kou
authors.initials: K
authors.lastname: Okuro
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Hoashi
authors.affiliation: Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.|Riken Center for Emergent Matter Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Takuzo
authors.initials: T
authors.lastname: Aida
mesh_terms: D004587:Electrophoresis, Agar Gel; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures; D010084:Oxidation-Reduction; D058105:Polymerization; D034741:RNA, Small Interfering / Q000008:administration & dosage*
chemical_list: D034741:RNA, Small Interfering