Cell-Specific Gene Transfer by α-Cyclodextrin Conjugates with Mannosylated Polyamidoamine Dendrimers

Abstract

To improve the activity and the cell specificity of gene transferof polyamidoamine starburst dendrimer, we prepared α-CyD conjugates with mannosylateddendrimers (generation 2 (G2), man-α-CDE conjugates) having various degrees of substitution(DS) of mannose residue. The man-α-CDE conjugates (DS 1, 3 and 5) formed complexeswith plasmid DNA (pDNA), but man-α-CDE conjugate (DS 8) did not. The gene transferactivity of man-α-CDE conjugates (DS 1, 3 and 5) and α-CDE conjugate was augmented with an increasein the charge ratio of vector/pDNA, without showing cytotoxicity. Man-α-CDE conjugates(DS 3 and 5) showed higher gene transfer activity than α-CDE conjugate in A549 cells, whichrecognize mannose, but man-α-CDE conjugates (DS 1 and 8) showed almost comparable gene transfer activityto α-CDE conjugate (G2). On the other hand, no appreciable enhancing effect of man-α-CDEconjugates (DS 3 and 5) on the transfer activity was observed in NIH3T3 cells, which do not recognizemannose. These findings suggest that man-α-CDE conjugates (DS 3 and 5) can be new preferablecell-specific non-viral vectors of pDNA to cells which recognize the mannose moiety.