Skip to main content
PMC home page
Biophysical Journal logoLink to Biophysical Journal
. 1998 May;74(5):2152–2158. doi: 10.1016/S0006-3495(98)77924-X

The importance of electric field distribution for effective in vivo electroporation of tissues.

D Miklavcic 1, K Beravs 1, D Semrov 1, M Cemazar 1, F Demsar 1, G Sersa 1
PMCID: PMC1299558  PMID: 9591642

Abstract

Cells exposed to short and intense electric pulses become permeable to a number of various ionic molecules. This phenomenon was termed electroporation or electropermeabilization and is widely used for in vitro drug delivery into the cells and gene transfection. Tissues can also be permeabilized. These new approaches based on electroporation are used for cancer treatment, i.e., electrochemotherapy, and in vivo gene transfection. In vivo electroporation is thus gaining even wider interest. However, electrode geometry and distribution were not yet adequately addressed. Most of the electrodes used so far were determined empirically. In our study we 1) designed two electrode sets that produce notably different distribution of electric field in tumor, 2) qualitatively evaluated current density distribution for both electrode sets by means of magnetic resonance current density imaging, 3) used three-dimensional finite element model to calculate values of electric field for both electrode sets, and 4) demonstrated the difference in electrochemotherapy effectiveness in mouse tumor model between the two electrode sets. The results of our study clearly demonstrate that numerical model is reliable and can be very useful in the additional search for electrodes that would make electrochemotherapy and in vivo electroporation in general more efficient. Our study also shows that better coverage of tumors with sufficiently high electric field is necessary for improved effectiveness of electrochemotherapy.

Full Text

The Full Text of this article is available as a PDF (261.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Belehradek J., Jr, Orlowski S., Poddevin B., Paoletti C., Mir L. M. Electrochemotherapy of spontaneous mammary tumours in mice. Eur J Cancer. 1991;27(1):73–76. doi: 10.1016/0277-5379(91)90065-l. [DOI] [PubMed] [Google Scholar]
  2. Belehradek J., Jr, Orlowski S., Ramirez L. H., Pron G., Poddevin B., Mir L. M. Electropermeabilization of cells in tissues assessed by the qualitative and quantitative electroloading of bleomycin. Biochim Biophys Acta. 1994 Feb 23;1190(1):155–163. doi: 10.1016/0005-2736(94)90045-0. [DOI] [PubMed] [Google Scholar]
  3. Belehradek M., Domenge C., Luboinski B., Orlowski S., Belehradek J., Jr, Mir L. M. Electrochemotherapy, a new antitumor treatment. First clinical phase I-II trial. Cancer. 1993 Dec 15;72(12):3694–3700. doi: 10.1002/1097-0142(19931215)72:12<3694::aid-cncr2820721222>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  4. Beravs K., White D., Sersa I., Demsar F. Electric current density imaging of bone by MRI. Magn Reson Imaging. 1997;15(8):909–915. doi: 10.1016/s0730-725x(97)00038-6. [DOI] [PubMed] [Google Scholar]
  5. Gallo S. A., Oseroff A. R., Johnson P. G., Hui S. W. Characterization of electric-pulse-induced permeabilization of porcine skin using surface electrodes. Biophys J. 1997 Jun;72(6):2805–2811. doi: 10.1016/S0006-3495(97)78922-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gilbert R. A., Jaroszeski M. J., Heller R. Novel electrode designs for electrochemotherapy. Biochim Biophys Acta. 1997 Feb 11;1334(1):9–14. doi: 10.1016/s0304-4165(96)00119-5. [DOI] [PubMed] [Google Scholar]
  7. Heller R., Jaroszeski M. J., Glass L. F., Messina J. L., Rapaport D. P., DeConti R. C., Fenske N. A., Gilbert R. A., Mir L. M., Reintgen D. S. Phase I/II trial for the treatment of cutaneous and subcutaneous tumors using electrochemotherapy. Cancer. 1996 Mar 1;77(5):964–971. doi: 10.1002/(sici)1097-0142(19960301)77:5<964::aid-cncr24>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  8. Heller R., Jaroszeski M., Atkin A., Moradpour D., Gilbert R., Wands J., Nicolau C. In vivo gene electroinjection and expression in rat liver. FEBS Lett. 1996 Jul 8;389(3):225–228. doi: 10.1016/0014-5793(96)00590-x. [DOI] [PubMed] [Google Scholar]
  9. Heller R., Jaroszeski M., Perrott R., Messina J., Gilbert R. Effective treatment of B16 melanoma by direct delivery of bleomycin using electrochemotherapy. Melanoma Res. 1997 Feb;7(1):10–18. doi: 10.1097/00008390-199702000-00003. [DOI] [PubMed] [Google Scholar]
  10. Hibino M., Shigemori M., Itoh H., Nagayama K., Kinosita K., Jr Membrane conductance of an electroporated cell analyzed by submicrosecond imaging of transmembrane potential. Biophys J. 1991 Jan;59(1):209–220. doi: 10.1016/S0006-3495(91)82212-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Joy M., Scott G., Henkelman M. In vivo detection of applied electric currents by magnetic resonance imaging. Magn Reson Imaging. 1989 Jan-Feb;7(1):89–94. doi: 10.1016/0730-725x(89)90328-7. [DOI] [PubMed] [Google Scholar]
  12. Kakorin S., Stoylov S. P., Neumann E. Electro-optics of membrane electroporation in diphenylhexatriene-doped lipid bilayer vesicles. Biophys Chem. 1996 Jan 16;58(1-2):109–116. doi: 10.1016/0301-4622(95)00090-9. [DOI] [PubMed] [Google Scholar]
  13. Kinosita K., Jr, Ashikawa I., Saita N., Yoshimura H., Itoh H., Nagayama K., Ikegami A. Electroporation of cell membrane visualized under a pulsed-laser fluorescence microscope. Biophys J. 1988 Jun;53(6):1015–1019. doi: 10.1016/S0006-3495(88)83181-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lee R. C., River L. P., Pan F. S., Ji L., Wollmann R. L. Surfactant-induced sealing of electropermeabilized skeletal muscle membranes in vivo. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4524–4528. doi: 10.1073/pnas.89.10.4524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mir L. M., Devauchelle P., Quintin-Colonna F., Delisle F., Doliger S., Fradelizi D., Belehradek J., Jr, Orlowski S. First clinical trial of cat soft-tissue sarcomas treatment by electrochemotherapy. Br J Cancer. 1997;76(12):1617–1622. doi: 10.1038/bjc.1997.606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mir L. M., Orlowski S., Belehradek J., Jr, Paoletti C. Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses. Eur J Cancer. 1991;27(1):68–72. doi: 10.1016/0277-5379(91)90064-k. [DOI] [PubMed] [Google Scholar]
  17. Mir L. M., Orlowski S., Poddevin B., Belehradek J., Jr Electrochemotherapy tumor treatment is improved by interleukin-2 stimulation of the host's defenses. Eur Cytokine Netw. 1992 May-Jun;3(3):331–334. [PubMed] [Google Scholar]
  18. Mir L. M., Roth C., Orlowski S., Quintin-Colonna F., Fradelizi D., Belehradek J., Jr, Kourilsky P. Systemic antitumor effects of electrochemotherapy combined with histoincompatible cells secreting interleukin-2. J Immunother Emphasis Tumor Immunol. 1995 Jan;17(1):30–38. doi: 10.1097/00002371-199501000-00004. [DOI] [PubMed] [Google Scholar]
  19. Neumann E., Schaefer-Ridder M., Wang Y., Hofschneider P. H. Gene transfer into mouse lyoma cells by electroporation in high electric fields. EMBO J. 1982;1(7):841–845. doi: 10.1002/j.1460-2075.1982.tb01257.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nishi T., Yoshizato K., Yamashiro S., Takeshima H., Sato K., Hamada K., Kitamura I., Yoshimura T., Saya H., Kuratsu J. High-efficiency in vivo gene transfer using intraarterial plasmid DNA injection following in vivo electroporation. Cancer Res. 1996 Mar 1;56(5):1050–1055. [PubMed] [Google Scholar]
  21. Okino M., Mohri H. Effects of a high-voltage electrical impulse and an anticancer drug on in vivo growing tumors. Jpn J Cancer Res. 1987 Dec;78(12):1319–1321. [PubMed] [Google Scholar]
  22. Orlowski S., Belehradek J., Jr, Paoletti C., Mir L. M. Transient electropermeabilization of cells in culture. Increase of the cytotoxicity of anticancer drugs. Biochem Pharmacol. 1988 Dec 15;37(24):4727–4733. doi: 10.1016/0006-2952(88)90344-9. [DOI] [PubMed] [Google Scholar]
  23. Pliquett U., Langer R., Weaver J. C. Changes in the passive electrical properties of human stratum corneum due to electroporation. Biochim Biophys Acta. 1995 Nov 1;1239(2):111–121. doi: 10.1016/0005-2736(95)00139-t. [DOI] [PubMed] [Google Scholar]
  24. Rols M. P., Teissié J. Electropermeabilization of mammalian cells. Quantitative analysis of the phenomenon. Biophys J. 1990 Nov;58(5):1089–1098. doi: 10.1016/S0006-3495(90)82451-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sersa G., Cemazar M., Menart V., Gaberc-Porekar V., Miklavcic D. Anti-tumor effectiveness of electrochemotherapy with bleomycin is increased by TNF-alpha on SA-1 tumors in mice. Cancer Lett. 1997 Jun 3;116(1):85–92. doi: 10.1016/s0304-3835(97)00170-5. [DOI] [PubMed] [Google Scholar]
  26. Sersa G., Cemazar M., Miklavcic D. Antitumor effectiveness of electrochemotherapy with cis-diamminedichloroplatinum(II) in mice. Cancer Res. 1995 Aug 1;55(15):3450–3455. [PubMed] [Google Scholar]
  27. Sersa I., Beravs K., Dodd N. J., Zhao S., Miklavcic D., Demsar F. Electric current density imaging of mice tumors. Magn Reson Med. 1997 Mar;37(3):404–409. doi: 10.1002/mrm.1910370318. [DOI] [PubMed] [Google Scholar]
  28. Tsong T. Y. Electroporation of cell membranes. Biophys J. 1991 Aug;60(2):297–306. doi: 10.1016/S0006-3495(91)82054-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Yang N. S., Sun W. H. Gene gun and other non-viral approaches for cancer gene therapy. Nat Med. 1995 May;1(5):481–483. doi: 10.1038/nm0595-481. [DOI] [PubMed] [Google Scholar]
  30. Zimmermann U. Electrical breakdown, electropermeabilization and electrofusion. Rev Physiol Biochem Pharmacol. 1986;105:176–256. [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES