title: Design and evaluation of thioalkylated mannose-modified dendrimer (G3)/α-cyclodextrin conjugates as antigen-presenting cell-selective siRNA carriers.
abstract: To design and evaluate the potential use of thioalkylated mannose-modified dendrimer (generation 3; G3) conjugates with α-cyclodextrin (Man-S-α-CDE (G3)) as novel antigen-presenting cell (APC)-selective siRNA carriers, we investigated the RNAi effects of siRNA complexes with Man-S-α-CDEs (G3). Man-S-α-CDE (G3, average degree of substitution of mannose (DSM) 4)/siRNA complex had the potent RNAi effects in both NR8383 cells, a rat alveolar macrophage cell line, and JAWSII cells, a mouse dendritic cell line, through adequate physicochemical properties, mannose receptor (MR)-mediated cellular uptake, and efficient phagosomal escape of the siRNA complex. In addition, cytotoxic activities of the siRNA complexes with α-CDE (G3, DS2) and Man-S-α-CDE (G3, DSM4) were almost negligible up to a charge ratio of 100 (carrier/siRNA). Taken together, these results suggest that Man-S-α-CDE (G3, DSM4) has the potential for a novel APC-selective siRNA carrier.
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Motoyama
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Mitsuyasu
authors.forename: Chiho
authors.initials: C
authors.lastname: Akao
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Ayumu
authors.initials: A
authors.lastname: Ohyama
authors.forename: Nana
authors.initials: N
authors.lastname: Sato
authors.forename: Taishi
authors.initials: T
authors.lastname: Higashi
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Arima
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D015195:Drug Design; D018014:Gene Transfer Techniques; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008358:Mannose / Q000737:chemistry*; D051379:Mice; D034622:RNA Interference / Q000187:drug effects; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D051381:Rats; D014162:Transfection; D047391:alpha-Cyclodextrins / Q000737:chemistry*
chemical_list: D050091:Dendrimers; D004337:Drug Carriers; D034741:RNA, Small Interfering; D047391:alpha-Cyclodextrins; D008358:Mannose; C032613:alpha-cyclodextrin