Oligobenzylethylenimine enriches linear polyethylenimine with a pH-sensitive membrane-disruptive property and leads to enhanced gene delivery activity

Acta Biomater. 2013 Feb;9(2):4985-93. doi: 10.1016/j.actbio.2012.09.015. Epub 2012 Sep 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aziridines / chemistry*
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism*
  • Cell Survival / drug effects
  • DNA / metabolism
  • Electrophoresis, Agar Gel
  • Gene Transfer Techniques*
  • Hemolysis / drug effects
  • Humans
  • Hydrogen-Ion Concentration / drug effects
  • Particle Size
  • Polyethyleneimine / analogs & derivatives*
  • Polyethyleneimine / chemical synthesis
  • Polyethyleneimine / chemistry*
  • Polyethyleneimine / pharmacology
  • Potentiometry
  • Sheep

Substances

  • Aziridines
  • oligo(benzylethylenimine)-b-polyethylenimine
  • aziridine
  • Polyethyleneimine
  • DNA