Cell-specific gene transfer by α-cyclodextrin conjugates with mannosylated polyamidoamine dendrimers

被引:15
作者
Arima, H [1 ]
Wada, K [1 ]
Kihara, F [1 ]
Tsutsumi, T [1 ]
Hirayama, F [1 ]
Uekama, K [1 ]
机构
[1] Kumamoto Univ, Fac Pharmaceut Sci, Kumamoto 8620973, Japan
关键词
cyclodextrin; dendrimer; gene transfer; mannose; targeting;
D O I
10.1023/A:1023092508646
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
To improve the activity and the cell specificity of gene transfer of polyamidoamine starburst dendrimer, we prepared alpha-CyD conjugates with mannosylated dendrimers (generation 2 (G2), man-alpha-CDE conjugates) having various degrees of substitution (DS) of mannose residue. The man-alpha-CDE conjugates (DS 1, 3 and 5) formed complexes with plasmid DNA (pDNA), but man-alpha-CDE conjugate (DS 8) did not. The gene transfer activity of man-alpha-CDE conjugates (DS 1, 3 and 5) and alpha-CDE conjugate was augmented with an increase in the charge ratio of vector/pDNA, without showing cytotoxicity. Man-alpha- CDE conjugates (DS 3 and 5) showed higher gene transfer activity than alpha-CDE conjugate in A549 cells, which recognize mannose, but man-alpha-CDE conjugates (DS 1 and 8) showed almost comparable gene transfer activity to alpha-CDE conjugate (G2). On the other hand, no appreciable enhancing effect of man-alpha-CDE conjugates (DS 3 and 5) on the transfer activity was observed in NIH3T3 cells, which do not recognize mannose. These findings suggest that man-alpha-CDE conjugates (DS 3 and 5) can be new preferable cell-specific non-viral vectors of pDNA to cells which recognize the mannose moiety.
引用
收藏
页码:361 / 364
页数:4
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