The use of high-frequency short bipolar pulses in cisplatin electrochemotherapy in vitro

Abstract

In electrochemotherapy, chemotherapeutic drugs are usually administered by intratumoral or intravenous injection, and then long monopolar pulses are delivered. However, long monopolar pulses can cause pain and muscle contractions. It is thus necessary to administer muscle relaxants, general anesthesia and to synchronize pulses with the heart rhythm of the patient which makes the treatment more complex and demanding. Recently, it was suggested that the use of bursts of short high-frequency bipolar pulses (HF-IRE) in irreversible electroporation could overcome these problems. The aim of our study was to verify if it is possible to use high-frequency bipolar pulses (HF-IRE for electrochemotherapy (reversible electroporation). We performed in vitro experiments on mouse skin melanoma (B16-F1) cells by first adding cisplatin and then delivering either (1) classical long monopolar pulses (100 µs) or (2) bursts of high-frequency short bipolar pulses (HF-EP). With both types of pulses, the combination of electric pulses with cisplatin was more efficient in killing cells than with only cisplatin or only electric pulses. However, we needed to apply higher electric field with high-frequency bipolar pulses (3 kV/cm) than with classical long monopolar pulses (1.2 kV/cm) in order to obtain comparable results. We can thus conclude that it is possible to use short bipolar pulses also in electrochemotherapy treatment, however, at the expense of applying higher electric fields than when using classical long monopolar pulses. The result obtained, nevertheless, pave the way to the use of high-frequency bipolar pulses in electrochemotherapy treatments with potentially alleviated muscle contractions and pain.