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Poly( L ‐histidine) with several aminoethyl groups for a new pH‐sensitive DNA carrier
Author(s) -
Asayama Shoichiro,
Sekine Takashi,
Hamaya Ai,
Kawakami Hiroyoshi,
Nagaoka Shoji
Publication year - 2005
Publication title -
polymers for advanced technologies
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.61
H-Index - 90
eISSN - 1099-1581
pISSN - 1042-7147
DOI - 10.1002/pat.616
Subject(s) - histidine , imidazole , transfection , dna , polylysine , deprotonation , protonation , gene delivery , in vitro , chemistry , hemolysis , membrane , biochemistry , biology , organic chemistry , enzyme , gene , ion , immunology
In this study, poly( L ‐histidine) with several aminoethyl groups, i.e. aminated poly( L ‐histidine), is reported to be able to make complexes with DNA and to transfect cells in vitro in the presence of serum. The present study was performed to determine whether the pH of the medium had an influence on the complex formation with DNA, on the cell membrane fusion activity and on the transfection efficiency. Agarose gel retardation assays proved that the polyion complex formation of the aminated poly( L ‐histidine) with DNA was affected by pH of the medium, owing to the basicity (protonation–deprotonation) of the imidazole groups with a p K a value around 6.0. Hemolysis assay showed that the resulting DNA complex enhanced membrane disruptive ability at endosomal pH. The aminated poly( L ‐histidine) gene carrier demonstrated significant transfection efficacy which was decreased by the inclusion of chloroquine as an endosomolytic agent. These results suggest that the aminated poly( L ‐histidine) promises to be a new pH‐sensitive DNA carrier for endosomal escape. Copyright © 2005 John Wiley & Sons, Ltd.