title: Design of comb-type polyamine copolymers for a novel pH-sensitive DNA carrier.
abstract: The comb-type polycation consisting of a poly[2-(diethylamino)ethyl methacrylate] (PDEAEMA) backbone and poly(L-lysine) (PLL) side chains has been prepared as a novel pH-sensitive DNA carrier. The comb-type copolymer PDEAEMA-graft-PLL was prepared by using the macromonomer method, in which a poly(N epsilon-carbobenzoxy-L-lysine) macromonomer was radically 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 titration. In addition, the comb-type copolymer caused no significant turbidity even at pH 10, whereas PDEAEMA homopolymer suddenly precipitated out of the aqueous medium above pH 7.5 owing to the deprotonation of amino groups. Furthermore, a 1H NMR study proved that protonated PLL segments solubilized the comb-type copolymer with a hydrophobic PDEAEMA core at higher pH. Finally, the pH-dependent behavior of the DNA complex with the comb-type copolymer was evaluated. The discontinuous turbidity change of the DNA/PDEAEMA-graft-PLL mixture at pH 7.5 suggested that the solubility of the complex varied in response to pH. By circular 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 sensing a pH signal and outputting the nonlinear change of the physicochemical properties of DNA polyelectrolyte complexes.
authors.affiliation: Department of Biomolecular Engineering, Tokyo Institute of Technology, Yokohama, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Asayama
authors.forename: A
authors.initials: A
authors.lastname: Maruyama
authors.forename: C S
authors.initials: CS
authors.lastname: Cho
authors.forename: T
authors.initials: T
authors.lastname: Akaike
mesh_terms: D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008689:Methacrylates / Q000008:administration & dosage / Q000032:analysis / Q000138:chemical synthesis* / Q000737:chemistry; D009690:Nucleic Acid Conformation; D009757:Nylons / Q000032:analysis / Q000138:chemical synthesis* / Q000737:chemistry; D011107:Polylysine / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D012680:Sensitivity and Specificity; D012995:Solubility
chemical_list: D004337:Drug Carriers; D008689:Methacrylates; D009757:Nylons; D011108:Polymers; C109846:poly(2-(diethylamino)ethyl methacrylate); D011107:Polylysine; D004247:DNA