title: Plasmid DNA-encapsulating liposomes: effect of a spacer between the cationic head group and hydrophobic moieties of the lipids on gene expression efficiency.
abstract: We have synthesized a series of cationic amino acid-based lipids having a spacer between the cationic head group and hydrophobic moieties and examined the influence of the spacer on a liposome gene delivery system. As a comparable spacer, a hydrophobic spacer with a hydrocarbon chain composed of 0, 3, 5, 7, or 11 carbons, and a hydrophilic spacer with an oxyethylene chain (10 carbon and 3 oxygen molecules) were investigated. Plasmid DNA (pDNA)-encapsulating liposomes were prepared by mixing an ethanol solution of the lipids with an aqueous solution of pDNA. The zeta potentials and cellular uptake efficiency of the cationic liposomes containing each synthetic lipid were almost equivalent. However, the cationic lipids with the hydrophobic spacer were subject to fuse with biomembrane-mimicking liposomes. 1,5-Dihexadecyl-N-lysyl-N-heptyl-l-glutamate, having a seven carbon atom spacer, exhibited the highest fusogenic potential among the synthetic lipids. Increased fusion potential correlated with enhanced gene expression efficiency. By contrast, an oxyethylene chain spacer showed low gene expression efficiency. We conclude that a hydrophobic spacer between the cationic head group and hydrophobic moieties is a key component for improving pDNA delivery.
authors.affiliation: Department of Life Science, Graduate School of Advanced Science and Engineering, Waseda University (TWIns), Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Obata
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Saito
authors.forename: Naoya
authors.initials: N
authors.lastname: Takeda
authors.forename: Shinji
authors.initials: S
authors.lastname: Takeoka
mesh_terms: D055592:Biophysical Phenomena; D002412:Cations / Q000737:chemistry; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D008561:Membrane Fusion; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics*
chemical_list: D002412:Cations; D008055:Lipids; D008081:Liposomes