In Vitro Electrochemotherapy Experiments to Quantify the Number of Cisplatin Molecules Needed for a Cytotoxic Effect When Different Types of Pulses Are Delivered

Electrochemotherapy treats various types of tumors by combining chemotherapeutic drugs, such as bleomycin or cisplatin, with the delivery of high-voltage pulses resulting in cell membrane electroporation. Conventionally 8 square monopolar pulses of 100 μs duration at a repetition frequency of 1 or 5000 Hz are delivered. Nevertheless, other types of high voltage pulses are being explored for electrochemotherapy and other electroporation-based applications, including a few μs long (high-frequency) bipolar pulses (shown to reduce muscle contractions and pain), and several ms long monopolar pulses (used for gene transfection). It remains unclear whether different types of pulses have any significant effect on drug uptake and cytotoxicity in the context of electrochemotherapy. Thus, the aim of this work was to experimentally quantify the number of cisplatin molecules needed to achieve a cytotoxic effect when different types of pulses are used. We tested three different types of pulses: (1) bursts of 2 μs bipolar pulses, (2) 100 μs monopolar pulses, and (3) 5 ms long monopolar pulses. Our results of in vitro electrochemotherapy experiments show that different number of cisplatin molecules is needed to achieve a comparable cytotoxic effect for the tested pulse types.