RRC ID 45299
Author Motoyama K, Mitsuyasu R, Akao C, Tanaka T, Ohyama A, Sato N, Higashi T, Arima H.
Title Design and evaluation of thioalkylated mannose-modified dendrimer (G3)/α-cyclodextrin conjugates as antigen-presenting cell-selective siRNA carriers.
Journal AAPS J
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.
Volume 16(6)
Pages 1298-308
Published 2014-11-1
DOI 10.1208/s12248-014-9665-9
PMID 25236864
PMC PMC4389755
MeSH Animals Antigen-Presenting Cells* / metabolism Cell Line Cell Survival / drug effects Dendrimers / chemistry* Dendritic Cells / drug effects Dendritic Cells / metabolism Drug Carriers / chemical synthesis Drug Carriers / chemistry* Drug Design* Gene Transfer Techniques Macrophages, Alveolar / drug effects Macrophages, Alveolar / metabolism Mannose / chemistry* Mice RNA Interference / drug effects RNA, Small Interfering / administration & dosage* RNA, Small Interfering / genetics Rats Transfection alpha-Cyclodextrins / chemistry*
IF 3.737
Times Cited 6
Human and Animal Cells Colon-26(RCB2657)