title: Novel biomimetic vectors with endosomal-escape agent enhancing gene transfection efficiency.
abstract: Low cytotoxicity and high transfection efficiency are critical issues in designing current non-viral gene delivery vectors. In the present study, a novel biomimetic lipid-polycation copolymer, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-graft-poly(l-lysine)-block-poly(ethylene glycol) (DOPE-g-PLL-b-PEG) was first synthesized and the potential of this novel hybrid lipid-polycation as efficient gene vector was further evaluated. DOPE-g-PLL-b-PEG and DNA could self-assemble into lipid modified polyion complex micelles (LPCM) through electrostatic interactions. Compared with PEG-b-PLL/DNA polyion complex micelles (PIC), LPCM could protect DNA from plasma, nuclease degradation in vitro and showed lower cytotoxicity to HepG2 and HeLa cells (P<0.05). The results of transfection study in vitro indicated that LPCM exhibited higher gene expression than PIC. Especially, the corresponding LPCM displayed the highest transfection efficiency in HeLa cells (P<0.05) when DOPE grafting ratio reached up to 30%. These results suggested that LPCM could facilitate gene transfer in cultured cells and might alleviate the drawbacks of the conventional cationic vector/DNA complexes. As a novel hybrid lipid-polycation, DOPE-g-PLL-b-PEG was valuable to be evaluated for its further application as gene carrier in vivo.
authors.affiliation: The School of Pharmaceutical Science, Shandong University, 44 Wenhua Xi Road, Ji'nan, Shandong Province 250012, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Sun
authors.forename: Chunxi
authors.initials: C
authors.lastname: Liu
authors.forename: Donghua
authors.initials: D
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
mesh_terms: D032701:Biomimetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D003850:Deoxyribonuclease I / Q000378:metabolism; D011992:Endosomes; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008823:Micelles; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000008:administration & dosage* / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D011107:Polylysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D014162:Transfection / Q000379:methods*
chemical_list: D008823:Micelles; D010714:Phosphatidylethanolamines; C443714:polylysine-graft-(poly(ethylene glycol)); D011107:Polylysine; D011092:Polyethylene Glycols; C020888:1,2-dielaidoylphosphatidylethanolamine; D004247:DNA; D003850:Deoxyribonuclease I