Bi-phasic polycation for the DNA carrier responding to endosomal pH

The bi-phasic polycation consisting of a poly(1-vinylimidazole) (PVIm) backbone and 'lactosylated' poly(L-lysine) (PLL) side-chains has been prepared as a DNA carrier with a proton-buffering effect at endosomal pHs 5-6). The comb-type copolymer PVIm-graft-PLL was prepared by using the macromonomer method. First, a poly(N-epsilon-carbobenzoxy-L-lysine) macromonomer was radically copolymerized with VIm. Then, the epsilon -amino groups of the PLL-grafts and the reducing end of lactose were covalently coupled by reductive amination. The resulting lactosylated Mm-graft-PLL comb-type copolymer (PVIm-graft-PLL . Lac) exhibited a dual ionic character owing to the two cationic segments in the copolymer, as determined by acid-base titration. Agarose gel retardation assays proved that the stronger basic segment PLL . Lac-grafts worked as the anchor segment for DNA/PVIm-graft-PLL . Lac complex formation. Turbidity measurements showed that the DNA/PVIm-graft-PLL . Lac complex exhibited a slight turbidity at physiological pH (= 7.4) and significant turbidity at endosomal pH, owing to the basicity (protonation-deprotonation) of the imidazole groups. It is worth noting that the solubility of the DNA/polycation complex in water decreased in spite of the increase of the net positive charges of DNA/polycation mixture. Due to the lactose groups, the interaction of DNA with the PLL . Lac-graft was different from that with unmodified PLL-graft. The difference of the interaction caused the solubility change of the DNA/polycation complex at endosomal pHs. (C) 2001 Elsevier Science B.V. All rights reserved.