Oxidation as a facile strategy to reduce the surface charge and toxicity of polyethyleneimine gene carriers

Wei Yang Seow, Kun Liang, Motoichi Kurisawa, Charlotte Hauser*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Polyethyleneimine (PEI) is widely regarded as one of the most efficient non-viral transfection agents commercially available. However, a key concern is its pronounced cytotoxicity, ascribed mainly to its high amine content and cationic charge density. Significant past efforts to mitigate its toxicity usually involved lengthy synthetic procedures. We now propose a simple strategy using hydrogen peroxide (H2O2) to oxidize the amine groups. PEI/DNA complexes were first formed before some amine groups were removed with H2O2. This reduced surface charge while the remaining cationic charges still allowed for efficient transfection. The DNA was not damaged and remained bound after oxidation. Furthermore, H 2O2 was quantitatively removed with sodium pyruvate prior to cell culture. Oxidized complexes caused no cytotoxicity even at high polymer concentrations. Compared to non-oxidized complexes used at subtoxic doses, oxidized complexes mediated significantly more GFP expression. A key strength of this approach is its simplicity as it involves only simple mixing of solutions. This strategy promises to further realize the potential of using PEI for the delivery of nucleic acids or other cargos.

Original languageEnglish (US)
Pages (from-to)2340-2346
Number of pages7
JournalBiomacromolecules
Volume14
Issue number7
DOIs
StatePublished - Jul 8 2013

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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