DESIGN OF COMB-TYPE POLYAMINE COPOLYMERS FOR A NOVEL PH-SENSITIVE DNACARRIER

The comb-type polycation consisting of a poly[2-(diethylamino)ethyl me thacrylate] (PDEAEMA) backbone and poly(L-lysine) (PLL) side chains ha s been prepared as a novel pH-sensitive DNA carrier. The comb-type cop olymer PDEAEMA-graft-PLL was prepared by using the macromonomer method , in which a poly(N-epsilon-carbobenzoxy-L-lysine) macromonomer was ra dically copolymerized with DEAEMA. The comb-type copolymer exhibited a two-step proton dissociation and a dual ionic character owing to the two cationic segments in the copolymer, as determined by acid-base tit ration. In addition, the comb-type copolymer caused no significant tur bidity even at pH 10, whereas PDEAEMA homopolymer suddenly precipitate d out of the aqueous medium above pH 7.5 owing to the deprotonation of amino groups. Furthermore, a H-1 NMR study proved that protonated PLL segments solubilized the comb-type copolymer with a hydrophobic PDEAE MA core at higher pH. Finally, the pH-dependent behavior of the DNA co mplex with the comb-type copolymer was evaluated. The discontinuous tu rbidity change of the DNA/PDEAEMA-graft-PLL mixture at pH 7.5 suggeste d that the solubility of the complex varied in response to pH. By circ ular dichroism measurement, we also found that the comb-type copolymer was capable of varying DNA compaction pH-dependently. In conclusion, we have demonstrated that the comb-type copolymer is capable of sensin g a pH signal and outputting the nonlinear change of the physicochemic al properties of DNA polyelectrolyte complexes.