Abstract
Electroporation—a transient electric-field-induced increase in cell membrane permeability—can be used to facilitate the delivery of anticancer drugs for antitumour electrochemotherapy. In recent years, Ca2+ electroporation has emerged as an alternative modality to electrochemotherapy. The antitumor effect of calcium electroporation is achieved as a result of the introduction of supraphysiological calcium doses. However, calcium is also known to play a key role in membrane resealing, potentially altering the pore dynamics and molecular delivery during electroporation. To elucidate the role of calcium for the electrotransfer of small charged molecule into cell we have performed experiments using nano- and micro-second electric pulses. The results demonstrate that extracellular calcium ions inhibit the electrotransfer of small charged molecules. Experiments revealed that this effect is related to an increased rate of membrane resealing. We also employed mathematical modelling methods in order to explain the differences between the CaCl2 effects after the application of nano- and micro-second duration electric pulses. Simulation showed that these differences occur due to the changes in transmembrane voltage generation in response to the increase in specific conductivity when CaCl2 concentration is increased.
Highlights
Electroporation is a physical method for exogenous molecule delivery through the plasma membrane that is used to increase the plasma membrane permeability by applying short but strong electric pulses [1]
The first set of experiments was designed to evaluate whether the addition of CaCl2 to the electroporation medium can have any influence on the Propidium iodide (PI) electrotransfer efficiency after microsecond range electroporation
These results show that CaCl2 reduce the efficiency of PI electrotransfer
Summary
Electroporation is a physical method for exogenous molecule delivery through the plasma membrane that is used to increase the plasma membrane permeability by applying short (ns–ms) but strong electric pulses [1]. The permeability is increased due to the electric-field-induced transmembrane voltage, resulting in the formation of transient hydrophilic pores in the cell membrane [2]. The presence of electropores—either reversible or irreversible—enables bidirectional transport across the cell membrane [7]. Such increased permeability can be used for the effective delivery of small charged molecules (e.g., fluorescent dyes [8] or membrane-impermeable chemotherapeutic drugs [9]) to the cells. A recent clinical trial has shown that calcium electroporation has comparable efficiency as electrochemotherapy and is feasible and effective in patients with cutaneous metastases [12]
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