Synthesis and characterization of alkylated poly(1-vinylimidazole) to control the stability of its DNA polyion complexes for gene delivery.
Poly(1-vinylimidazole) (PVIm) with alkylated imidazole groups has been synthesized as a pH-sensitive polycation to control the stability of its DNA polyion complexes for gene delivery. The resulting alkylated PVIm (PVIm-R) was water-soluble despite deprotonation of the imidazole groups at physiological pH, as determined by acid-base titration and solution turbidity measurements. Agarose gel retardation assay proved that the alkylated imidazole groups worked as anchor groups to retain DNA. Pyrene fluorescence measurement showed that the hydrophobic domain of the DNA complex with butylated PVIm (PVIm-Bu) increased after the protonation of imidazole groups of the PVIm-Bu to enhance the membrane disruptive activity. The PVIm-Bu exhibited no significant cytotoxicity in spite of the existence of cationic groups. The resulting PVIm-Bu/DNA complexes easily released DNA, as compared with the octylated PVIm, which was examined by competitive exchange with dextran sulfate. As a result, the PVIm-R/DNA complexes mediated efficient gene delivery, and the gene expression depended on the length and density of the alkyl chains. These results suggest that pH-sensitive PVIm-R's control of the stability of DNA polyion complexes enhanced noncytotoxic gene delivery by the optimized alkylated imidazole groups.
Asayama
Shoichiro
S
Department of Applied Chemistry, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo 192-0397, Japan. asayama-shoichiro@c.metro-u.ac.jp
Hakamatani
Tomoe
T
Kawakami
Hiroyoshi
H
D000478:Alkylation; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D018014:Gene Transfer Techniques; D006461:Hemolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry*; D007477:Ions / Q000737:chemistry; D011145:Polyvinyls / Q000138:chemical synthesis* / Q000737:chemistry*; D013329:Structure-Activity Relationship
D007093:Imidazoles; D007477:Ions; D011145:Polyvinyls; C524090:poly(1-vinylimidazole); C029899:imidazole; D004247:DNA