期刊
BIOCONJUGATE CHEMISTRY
卷 18, 期 4, 页码 1349-1354出版社
AMER CHEMICAL SOC
DOI: 10.1021/bc060311k
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We recently developed a novel family of cationic lipids consisting of a polyamidoamine (PAMAM) dendron and two dodecyl chains. Their transfection activity increases with increasing generation of the dendron moiety [Takahashi et al. (2003) Bioconjugate Chem. 14, 764-773]. In the present study, to elucidate the effect of hydrophobic tail moieties of the dendron-bearing lipids, two kinds of PAMAM G3 dendron-bearing lipids were synthesized with different alkyl lengths, DL-G3-2C(18) and DL-G3-2C(12). Their functions as gene vectors were compared. Irrespective of their different alkyl chain lengths, these dendron-bearing lipids formed complexes with plasmid DNA with similar efficiency. However, their complex sizes differed markedly: DL-G3-2C(18) lipoplexes exhibited much smaller diameters than DL-G3-2C(12) lipoplexes. Interaction of the lipoplexes with heparin revealed that the DL-G3-2C(18) lipoplexes required more heparin than DL-G3-2C(12) lipoplexes to cause dissociation of plasmid DNA from the lipoplexes. Although the DL-G3-2C(12) lipoplexes and DL-G3-2C(18) lipoplexes transfected CV1 cells with similar efficiency in the absence of serum, only the latter retained high transfection activity in the presence of serum. These results indicate that hydrophobic interaction of alkyl chain moieties plays an important role in the increment of stability and the serum-resistant transfection activity for dendron-bearing lipid lipoplexes.
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