Abstract

BackgroundElectrochemotherapy and gene electrotransfer are novel promising treatments employing locally applied high electric pulses to introduce chemotherapeutic drugs into tumor cells or genes into target cells based on the cell membrane electroporation. The main focus of this paper was to calculate analytically and numerically local electric field distribution inside the treated tissue in two dimensional (2D) models for different plate and needle electrode configurations and to compare the local electric field distribution to parameter U/d, which is widely used in electrochemotherapy and gene electrotransfer studies. We demonstrate the importance of evaluating the local electric field distribution in electrochemotherapy and gene electrotransfer.MethodsWe analytically and numerically analyze electric field distribution based on 2D models for electrodes and electrode configurations which are most widely used in electrochemotherapy and gene electrotransfer. Analytical calculations were performed by solving the Laplace equation and numerical calculations by means of finite element method in two dimensions.ResultsWe determine the minimal and maximal E inside the target tissue as well as the maximal E over the entire treated tissue for the given electrode configurations. By comparing the local electric field distribution calculated for different electrode configurations to the ratio U/d, we show that the parameter U/d can differ significantly from the actual calculated values of the local electric field inside the treated tissue. By calculating the needed voltage to obtain E > U/d inside the target tissue, we showed that better electric field distribution can be obtained by increasing the number and changing the arrangement of the electrodes.ConclusionBased on our analytical and numerical models of the local electric field distribution we show that the applied voltage, configuration of the electrodes and electrode position need to be chosen specifically for each individual case, and that numerical modeling can be used to optimize the appropriate electrode configuration and adequate voltage. Using numerical models we further calculate the needed voltage for a specific electrode configuration to achieve adequate E inside the target tissue while minimizing damages of the surrounding tissue. We present also analytical solutions, which provide a convenient, rapid, but approximate method for a pre-analysis of electric field distribution in treated tissue.

Highlights

  • Electrochemotherapy and gene electrotransfer are novel promising treatments employing locally applied high electric pulses to introduce chemotherapeutic drugs into tumor cells or genes into target cells based on the cell membrane electroporation

  • Reversible electropermeabilization has been proven to be successful in electrochemotherapy, where electric field enables chemotherapeutic drug to enter into tumor cells, and for gene electrotransfer, which can be used for gene therapy, where electric field enables DNA to enter the target cells

  • The criteria for adequate or »optimal« local E distribution are the following: i) all the target tissue has to be exposed to the E above the threshold value for reversible electroporation (Ettmin> exceeds reversible threshold value (Erev)); ii) the maximal E inside the target tissue Ettmax has to be below the threshold value for irreversible electroporation (Ettmax< E reaches irreversible threshold value (Eirrev)), which is specially important in gene electrotransfer and iii) the surrounding tissue should not be exposed to excessively high electric field, the maxi

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Summary

Introduction

Electrochemotherapy and gene electrotransfer are novel promising treatments employing locally applied high electric pulses to introduce chemotherapeutic drugs into tumor cells or genes into target cells based on the cell membrane electroporation. Electropermeabilization is a phenomenon, where the membrane becomes permeable after the magnitude of the electric field (E) exceeds reversible threshold value (Erev), while E below Erev does not significantly affect the cell membrane. When the magnitude of local electric field E reaches irreversible threshold value (Eirrev), electric field causes permanent damages on the cell membrane leading to cell death. Reversible electropermeabilization has been proven to be successful in electrochemotherapy, where electric field enables chemotherapeutic drug to enter into tumor cells, and for gene electrotransfer, which can be used for gene therapy, where electric field enables DNA to enter the target cells. Irreversible electroporation with E > Eirrev was suggested for water treatment and food preservation as a method for destruction of the cell membrane of noxious microorganisms and for tissue ablation [20,21,22]

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