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Macromol Biosci. 2005 Jun 24;5(6):512-9.

Folate receptor-mediated gene delivery using folate-poly(ethylene glycol)-poly(L-lysine) conjugate.

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  • 1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.

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.

[PubMed - indexed for MEDLINE]
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