TY - JOUR
T1 - Folate receptor-mediated gene delivery using folate-poly(ethylene glycol)-poly(L-lysine) conjugate
AU - Cho, Kyung Chul
AU - Kim, Sun Hwa
AU - Jeong, Ji Hoon
AU - Park, Tae Gwan
PY - 2005/6/24
Y1 - 2005/6/24
N2 - 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.
AB - 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.
KW - Folate
KW - Gene delivery
KW - Poly(ethylenimine) (PEI)
KW - Receptor-mediated endocytosis
UR - http://www.scopus.com/inward/record.url?scp=21644487837&partnerID=8YFLogxK
U2 - 10.1002/mabi.200500018
DO - 10.1002/mabi.200500018
M3 - Article
C2 - 15948228
AN - SCOPUS:21644487837
SN - 1616-5187
VL - 5
SP - 512
EP - 519
JO - Macromolecular Bioscience
JF - Macromolecular Bioscience
IS - 6
ER -