title: Oligobenzylethylenimine enriches linear polyethylenimine with a pH-sensitive membrane-disruptive property and leads to enhanced gene delivery activity.
abstract: We report here the synthesis of a diblock linear polymer of oligo(benzylethylenimine)-b-polyethylenimine (OBzEI-PEI) and investigate its gene delivery properties. The linear copolymer OBzEI-PEI was prepared in a straightforward manner by acidic hydrolysis of a diblock polyoxazoline, which had been made by sequential polymerization of 4-benzyl-2-ethyl-2-oxazoline followed by 2-ethyl-2-oxazoline. pH titration and DNA complexation profiles of the new polymer are similar to regular linear PEIs, but with higher gene transfection efficiencies in various cell lines despite a decreased cellular uptake of plasmid DNA. Further experiments suggest that the OBzEI tail complements the intrinsic proton-sponge endosomolytic activities of PEI with an acid pH-sensitive membrane-perturbing activity.
authors.affiliation: Laboratoire de Conception et Application de Molécules Bioactives, CNRS-Université de Strasbourg UMR 7199, Faculté de Pharmacie, 74 Route du Rhin, 67400 Illkirch, France.
authors.forename: Chittimalla
authors.initials: C
authors.lastname: Chandrashekhar
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Pons
authors.forename: Christian D
authors.initials: CD
authors.lastname: Muller
authors.forename: Nassera
authors.initials: N
authors.lastname: Tounsi
authors.forename: Rita
authors.initials: R
authors.lastname: Mulherkar
authors.forename: Guy
authors.initials: G
authors.lastname: Zuber
mesh_terms: D000818:Animals; D001388:Aziridines / Q000737:chemistry*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D018014:Gene Transfer Techniques; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D010316:Particle Size; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011199:Potentiometry; D012756:Sheep
chemical_list: D001388:Aziridines; C581570:oligo(benzylethylenimine)-b-polyethylenimine; C033132:aziridine; D011094:Polyethyleneimine; D004247:DNA