ABSTRACT

The term electroporation (EP) (also known as electropermeabilization) was originally coined to describe a method and process to temporarily permeabilize lipid membranes, including cellular membranes, by exposing such membranes to electric elds of sufcient magnitude and duration.1 On the one hand, the development of EP was based on earlier observations that the permeability of articial and biological membranes temporarily increases for ions and molecules when these membranes are subjected to short pulses of strong electric elds.2,3 On the other hand, the development was prompted by the need of the then emerging eld of genetic engineering for a more efcient, less cumbersome technique to transfect cells, that is, to introduce “foreign” DNA into cells. After the rst publication describing highly effective transfection and stable transformation of mammalian cells by in vitro EP,1 this new method quickly replaced earlier, less effective or more cumbersome ones. EP has since proven invaluable for the advancement of biological science, has given rise to new medical research and treatments, and has spawned applications in other elds. For example, DNA delivery by EP has become the preferred procedure for gene therapy and DNA vaccines, respectively, due to advantages over early chemical and viral DNA transfer methods.4 Another early and successful medical application involves the in vivo delivery of anti-cancer

drugs into cancer cells.5 EP has proven highly effective in increasing trans-membrane ux by two to four orders of magnitude without causing signicant side effects.6 This application has created the new eld of electrochemotherapy (ECT). Particularly in Europe, ECT is now increasingly accepted for routine clinical use, mostly in the palliative treatment of cancerous tumors, including cases where traditional therapies are not feasible or advisable.7 More recently, EP methods employing electric pulses of higher eld strength than those used for DNA or anti-cancer drug delivery have demonstrated, in initial clinical studies, their potential for nonthermal tissue ablation without a drug.8 Higher eld strengths induce necrotic and/or programmed (apoptotic) cell death selectively in the targeted tissue while sparing tissue scaffolds, in contrast to treatments based on thermal effects. Ablative techniques based on EP may be applied to a variety of therapies, including cancer and vascular therapies.8 Other medical areas that either already benet from EP, or may benet from ongoing research in the future, include intra-or trans-dermal delivery of therapeutic substances, insertion of agents into membranes, electro-encapsulation, and others.9