trans-2-Aminocyclohexanol-based amphiphiles as highly efficient helper lipids for gene delivery by lipoplexes
| Autor: | Yu Zheng, Xin Liu, Nataliya M. Samoshina, Vyacheslav V. Samoshin, Andreas H. Franz, Xin Guo |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Biophysics
Molecular Conformation Gene delivery Transfection Biochemistry HeLa Mice Conformational switch Cell Line Tumor Amphiphile Moiety Animals Humans Cationic liposome Lipid bilayer Cytotoxicity Luciferases biology Gene Transfer Techniques pH-sensitive Cell Biology Hydrogen-Ion Concentration biology.organism_classification Cyclohexanols Lipids Helper lipid lipids (amino acids peptides and proteins) |
| Zdroj: | Biochimica et biophysica acta. 1848(12) |
| ISSN: | 0006-3002 |
| Popis: | Lipidic amphiphiles equipped with the trans-2-aminocyclohexanol (TACH) moiety are promising pH-sensitive conformational switches (“flipids”) that can trigger a lipid bilayer perturbation in response to increased acidity. Because pH-sensitivity was shown to improve the efficiency of several gene delivery systems, we expected that such flipids could significantly enhance the gene transfection by lipoplexes. Thus a series of novel lipids with various TACH-based head groups and hydrocarbon tails were designed, prepared and incorporated into lipoplexes that contain the cationic lipid 1,2-dioleoyl-3-trimethylammonio-propane (DOTAP) and plasmid DNA encoding a luciferase gene. B16F1 and HeLa cells were transfected with such lipoplexes in both serum-free and serum-containing media. The lipoplexes consisting of TACH-lipids exhibited up to two orders of magnitude better transfection efficiency and yet similar toxicity compared to the ones with the conventional helper lipids 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol. Thus, the TACH-lipids can be used as novel helper lipids for efficient gene transfection with low cytotoxicity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|