Synthesis of aminated poly(1-vinylimidazole) for a new pH-sensitive DNA carrier.
The poly(1-vinylimidazole) (PVIm) with aminoethyl groups has been synthesized as a new pH-sensitive DNA carrier. The resulting aminated PVIm (PVIm-NH2) was water-soluble in spite of the deprotonation of the imidazole groups at physiological pH, as determined by acid-base titration and solution turbidity measurement. Hemolysis assay showed the PVIm-NH2 enhanced membrane disruptive ability at endosomal pH, owing to the protonation of the imidazole groups with a pKa value around 6.0. Agarose gel retardation assay proved that the introduced aminoethyl groups worked as an anchor groups to retain DNA. The resulting PVIm-NH2 formed the ternary complex with DNA and lactosylated poly(L-lysine), leading to the significant gene expression in human hepatoma HepG2 cells.
Asayama
Shoichiro
S
Department of Applied Chemistry, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo192-0397, Japan. asayama-shoichiro@c.metro-u.ac.jp
Sekine
Takashi
T
Kawakami
Hiroyoshi
H
Nagaoka
Shoji
S
D000588:Amines / Q000737:chemistry; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D005690:Galactose / Q000737:chemistry; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry*; D008024:Ligands; D011145:Polyvinyls / Q000138:chemical synthesis / Q000737:chemistry*
D000588:Amines; D002412:Cations; D007093:Imidazoles; D008024:Ligands; D011145:Polyvinyls; C524090:poly(1-vinylimidazole); D004247:DNA; D005690:Galactose