Facilitation of electroporative drug uptake and cell killing by electrosensitization
Article first published online: 11 JAN 2013
© 2012 The Authors Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Journal of Cellular and Molecular Medicine
Volume 17, Issue 1, pages 154–159, January 2013
How to Cite
Pakhomova, O. N., Gregory, B. W. and Pakhomov, A. G. (2013), Facilitation of electroporative drug uptake and cell killing by electrosensitization. Journal of Cellular and Molecular Medicine, 17: 154–159. doi: 10.1111/j.1582-4934.2012.01658.x
- Issue published online: 29 JAN 2013
- Article first published online: 11 JAN 2013
- Manuscript Accepted: 11 OCT 2012
- Manuscript Received: 6 APR 2012
- National Institutes of Health
- electric pulses;
- membrane permeability;
Cell permeabilization by electric pulses (EP), or electroporation, is widely used for intracellular delivery of drugs and plasmids, as well as for tumour and tissue ablation. We found that cells pre-treated with 100-μs EP develop delayed hypersensitivity to subsequent EP applications. Sensitizing B16 and CHO cells by splitting a single train of eight 100-μs EP into two trains of four EP each (with 5-min. interval) decreased the LD50 1.5–2 times. Sensitization profoundly enhanced the electroporation-assisted uptake of bleomycin, a cell-impermeable cytotoxic agent accepted for killing tumours by electrochemotherapy. EP exposures that were not lethal per se caused cell death in the presence of bleomycin and proportionally to its concentration. Sensitizing cells by a split-dose EP exposure increased bleomycin-mediated lethality to the same extent as a 10-fold increase in bleomycin concentration when using a single EP dose. Likewise, sensitization by a split-dose EP exposure (without changing the overall dose, pulse number, or amplitude) enhanced the electroporative uptake of propidium up to fivefold. Enhancement of the electroporative uptake appears a key mechanism of electrosensitization and may benefit electrochemotherapy and numerous applications that employ EP for cell permeabilization.