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

• Published in: Journal of controlled release Vol. 160; no. 3; pp. 552 - 560
• Main Authors: Yuba, Eiji, Nakajima, Yosuke, Tsukamoto, Kota, Iwashita, Shinki, Kojima, Chie, Harada, Atsushi, Kono, Kenji
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 28.06.2012; Elsevier
• Subjects: Biological and medical sciences; blood serum; Dendrimers - administration & dosage; Dendrimers - chemistry; Dendron-based lipid; DNA - administration & dosage; DNA - genetics; Gene delivery; General pharmacology; genes; Green Fluorescent Proteins - genetics; HeLa Cells; Humans; lipids; Liposomes; Luciferases - genetics; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phosphatidylethanolamines - administration & dosage; Phosphatidylethanolamines - chemistry; Plasmids; Poly(amidoamine) dendrimer; Rhodamines - administration & dosage; Rhodamines - chemistry; toxicity; Transfection; Transfection - methods; Unsaturated bond; Unsaturated bond; Gene delivery; Poly(amidoamine) dendrimer; Transfection; Dendron-based lipid; Dendrimer; Pharmaceutical technology; Branched polymer; Lipids; Genetic transfer; Amidoamine polymer; Alkyl; Gene therapy; Dendritic structure
• ISSN: 0168-3659; 1873-4995; 1873-4995
• DOI: 10.1016/j.jconrel.2012.04.002

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-G1-2C18, 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-G1-2C18-U2, which consists of the same dendron-moiety and two octadecenyl chains. DL-G1-2C18-U2 showed a higher ability to form lipoplexes with plasmid DNA than DL-G1-2C18. The DL-G1-2C18-U2 lipoplexes exhibited much smaller particle sizes than the DL-G1-2C18. In addition, the DL-G1-2C18-U2 lipoplexes exhibited more efficient transfection of HeLa cells than DL-G1-2C18 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-G1-2C18-U2 lipoplexes achieved the highly efficient transfection of the cells without marked cellular toxicity, in the presence of serum. Therefore, DL-G1-2C18-U2 might be promising as a potent gene vector. Dendron-based lipid having unsaturated bonds (DL-G1-U2) form the smaller complexes with pDNA and induce higher transgene expression than its counterpart lipid not having unsaturated bond (DL-G1). [Display omitted]