title: Folate receptor-mediated gene delivery using folate-poly(ethylene glycol)-poly(L-lysine) conjugate.
abstract: For efficient receptor-mediated gene transfection, a new and simple formulation method based on using PEI and FOLPEGPLL conjugate was presented. Luciferase plasmid DNA and PEI were complexed to form slightly positive-charged nanoparticles, onto which FOL-PEG-PLL conjugate was surface coated. With increasing the coating amount of FOL-PEG-PLL conjugate, the FOL-PEG-PLL/PEI/DNA complexes exhibited increased surface zeta-potential values with concomitantly increased diameters, indicating that the PLL part was physically anchored on the surface of preformed PEI/DNA complexes with FOL moieties being exposed on the outside. The formulated complexes exhibited a considerably higher transfection efficiency against FOL receptor over-expressing KB cells than FOL receptor deficient A549 cells. This was caused by an enhanced cellular uptake of the resultant complexes via a receptor-mediated endocytosis process. The formulated complexes showed a higher gene expression level, even in the presence of serum, than the PEI/DNA or Lipofectamine/DNA complexes. This was attributed to the PEG chains present on the surface of complexes that could work as a protective shield layer against aggregation caused by non-specific protein adsorption. The FOL-PEG-PLL/PEI/DNA complexes also demonstrated better cell viability than the PEI/DNA complexes.(1)H NMR spectrum of FOL-PEG-PLL conjugate.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
authors.forename: Kyung Chul
authors.initials: KC
authors.lastname: Cho
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Kim
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Tae Gwan
authors.initials: TG
authors.lastname: Park
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis; D002352:Carrier Proteins; D045744:Cell Line, Tumor; D002470:Cell Survival; D003850:Deoxyribonuclease I; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000737:chemistry; D018014:Gene Transfer Techniques; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011092:Polyethylene Glycols / Q000737:chemistry; D011107:Polylysine / Q000737:chemistry; D011956:Receptors, Cell Surface; D013997:Time Factors
chemical_list: D001672:Biocompatible Materials; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D011107:Polylysine; D011092:Polyethylene Glycols; D005492:Folic Acid; D003850:Deoxyribonuclease I