Preparation and evaluation of polyamidoamine dendrimer conjugate with glucuronylglucosyl-β-cyclodextrin (G3) as a novel carrier for siRNA.

Abstract In this study, we newly synthesized the polyamidoamine STARBURST dendrimer (dendrimer, generation 3: G3) conjugates with 6-O-α-(4-O-α-D-glucuronyl)-D-glucosyl-β-cyclodextrin [GUG-β-CDE (G3)] having the various degrees of substitution (DS) of GUG-β-cyclodextrin of 1.6, 3.0, 3.7, 5.0 and 8.6, and evaluated them as a siRNA transfer carrier. GUG-β-CDEs (G3) formed the positively charged and nano-order complexes with siRNA. Of the siRNA complexes with five GUG-β-CDEs (G3), the complex with GUG-β-CDE (G3, DS 3.7) showed the highest RNAi effect and cellular uptake with negligible cytotoxicity in KB cells at a charge ratio of 20. In addition, the RNAi effect and cellular uptake of the complex with GUG-β-CDE (G3, DS 3.7) were higher than those of α-CDE (G3, DS 2.4) and comparable to those of Lipofectamine™ 2000. Furthermore, the complex with GUG-β-CDE (G3, DS 3.7) possessed the endosomal escaping ability, the releasing property of siRNA in the cytoplasm and serum resistance. These results suggest that GUG-β-CDE (G3, DS 3.7) has the potential as a novel siRNA carrier.