Oxidation as a facile strategy to reduce the surface charge and toxicity of polyethyleneimine gene carriers
W.Y. Seow, K. Liang, M. Kurisawa, and C.A.E. Hauser
Biomacromolecules, 14 (2013) 2340-2346
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 simply 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, H2O2 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 solution. This strategy promises to further realize the potential of using PEI for the delivery of nucleic acids or other cargos.
"KAUST shall be a beacon for peace, hope and reconciliation, and shall serve the people of the Kingdom and the world."
King Abdullah bin Abdulaziz Al Saud, 1924 – 2015
Thuwal 23955-6900, Kingdom of Saudi Arabia
Al-Haytham Building (Bldg. 2)