Abstract
The purpose of this study is to evaluate the potential use of polyamidoamine (PAMAM) starburst dendrimer (generation 2, G2) conjugates with 6-O-α-(4-O-α-d-glucuronyl)-d-glucosyl-β-cyclodextrin (GUG-β-CDE (G2)) having glucose as a spacer between dendrimer and cyclodextrin (CyD) as a novel gene transfer carrier. GUG-β-CDE (G2) was found to have lower hemolytic activity than dendrimer (G2), suggesting that GUG-β-CDE (G2) had lower local irritation than dendrimer (G2). Of GUG-β-CDEs (G2) having the various average degree of substitution (DS) of a glucuronylglycoside group, GUG-β-CDE (G2, DS 1.8) possessed much higher gene transfer activity than α-CDE (G2, DS 1.2) and β-CDE (G2, DS 1.3) in A549 and RAW264.7 cells, suggesting the crucial role of a spacer between dendrimer and CyD for high gene transfer activity of GUG-β-CDE (G2, DS 1.8). In sharp contrast to linear polyethyleneimine (10 kDa, PEI), GUG-β-CDE (G2, DS 1.8) had negligible cytotoxicity. These results suggest that GUG-β-CDE (G2, DS 1.8) could have the potential for a novel gene transfer carrier, compared to α-CDE (G2, DS 1.2), β-CDE (G2, DS 1.3) and PEI.
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