Applications and Control of High Voltage Pulse Delivery for Tumor Therapy and Gene Therapy in vivo

Abstract

External electric fields applied to biological materials interact directly on free electric charges such as electrons and ions as well as on ionic groups in larger molecules. They also interact with dipoles such as water and induce dipoles in molecules with polarizable groups. The cell membranes seem to be the critical target for interaction causing intra-molecular transitions and intermolecular processes that lead to structural reorganization of the cell membranes. Applying high voltage pulses to cells in cultures or in tissue cause various degrees of structural reorganizations in the cell membranes, which might end with a dielectric collapse or breakdown. This condition is either called electroporation or electropermeabilization and can be reversible or irreversible depending on the characteristics of applied voltage pulses (Zimmermann and Neil, 1996;Zimmermann, 1982; Zimmermann et al. 1981; Zimmermann et al. 1974;Stampfli, 1958). In such a transient state, the membrane become permeable to molecules that normally doesn’t pass this barrier into the cytoplasm of the cell. This condition can be used for direct transfer of genes, other nucleic acids, proteins, and other molecules into cells and microorganisms. Another possibility is that neighbor cells with membranes in transient state might fuse together and form a new giant cell. These properties of membranes in transient state has led to electric field pulse techniques which have gained increasing importance in cellular and molecular biology, in gene technology and in various medical therapeutic procedures (Neumann et al. 1989). The effect of permeabilizing cell membranes by applied electric pulses is widely used in biochemistry, genetics and cell biology to introduce exogenous, membrane insoluble molecules into cells. The requirement for high efficiency of electropermeabilization and molecular transfection depends on the membrane dielectric properties, cell-shape and size, as well as pulse parameters such as shape, amplitude, length and number of pulses.