Abstract
The purpose of this study is to evaluate in vitro gene delivery efficiency of polyamidoamine (PAMAM) starburst dendrimer (generation 3, G3) conjugates with α-cyclodextrin (α-CDE (G3)) bearing lactose (Lac-α-CDE) with various degrees of substitution of the lactose moiety (DSL) as a novel hepatocyte-selective carrier. Lac-α-CDE (G3, DSL 1.2) was found to have much higher gene transfer activity than α-CDE (G3), Lac-α-CDE (G2, DSL 2.6) and Lac-α-CDEs (G3, DSL 2.6, 4.1 and 6.1) in HepG2 cells, which are dependent on the expression of cell-surface asialoglycoprotein receptor (ASGP-R). Lac-α-CDE (G3, DSL 1.2) provided negligible cytotoxicity up to a charge ratio of 100 (carrier/pDNA) in HepG2 cells. These results suggest the potential use of Lac-α-CDE (G3, DSL 1.2) as a non-viral vector for gene delivery toward hepatocytes.
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