Effect of unsaturated alkyl chains on transfection activity of poly(amidoamine) dendron-bearing lipids.

In an earlier study, we developed a new type of gene vector using poly(amidoamine) (PAMAM) dendron-bearing lipids and reported that their transfection activity was affected by their structures, such as dendron generation and alkyl chain length. In this study, for improvement of their performance as gene vectors, we examined the effect of unsaturated chains of the dendron-bearing lipids using DL-G1-2C(18), which consists of PAMAM G1 dendron moiety and two octadecyl chains, and achieved the most efficient transfection activity among the dendron-bearing lipids having saturated alkyl chains, and DL-G1-2C(18)-U2, which consists of the same dendron-moiety and two octadecenyl chains. DL-G1-2C(18)-U2 showed a higher ability to form lipoplexes with plasmid DNA than DL-G1-2C(18). The DL-G1-2C(18)-U2 lipoplexes exhibited much smaller particle sizes than the DL-G1-2C(18). In addition, the DL-G1-2C(18)-U2 lipoplexes exhibited more efficient transfection of HeLa cells than DL-G1-2C(18) did. Results demonstrate the importance of unsaturated chains for the production of the dendron-bearing lipids having excellent gene transfection performance. Without the help of additional fusogenic lipids such as dioleoylphosphatidylethanolamine, DL-G1-2C(18)-U2 lipoplexes achieved the highly efficient transfection of the cells without marked cellular toxicity, in the presence of serum. Therefore, DL-G1-2C(18)-U2 might be promising as a potent gene vector.