Micro- and Nanosecond Pulses Used in Doxorubicin Electrochemotherapy in Human Breast and Colon Cancer Cells with Drug Resistance

Abstract

(1) Background: Pulsed electric field (PEF) techniques are commonly used to support the delivery of various molecules. A PEF seems a promising method for low permeability drugs or when cells demonstrate therapy resistance and the cell membrane becomes an impermeable barrier. (2) Methods: In this study, we have used doxorubicin-resistant and sensitive models of human breast cancer (MCF-7/DX, MCF-7/WT) and colon cancer cells (LoVo, LoVoDX). The study aimed to investigate the susceptibility of the cells to doxorubicin (DOX) and electric fields in the 20–900 ns pulse duration range. The viability assay was utilized to evaluate the PEF protocols’ efficacy. Cell confluency and reduced glutathione were measured after PEF protocols. (3) Results: The obtained results showed that PEFs significantly supported doxorubicin delivery and cytotoxicity after 48 and 72 h. The 60 kV/cm ultrashort pulses × 20 ns × 400 had the most significant cytotoxic anticancer effect. The increase in DOX concentration provokes a decrease in cell viability, affected cell confluency, and reduced GSSH when combined with the ESOPE (European Standard Operating Procedures of Electrochemotherapy) protocol. Additionally, reactive oxygen species after PEF and PEF-DOX were detected. (4) Conclusions: Ultrashort electric pulses with low DOX content or ESOPE with higher DOX content seem the most promising in colon and breast cancer treatment.

Enhanced Cellular Doxorubicin Uptake via Delayed Exposure Following Nanosecond Pulsed Electric Field Treatment: An In Vitro Study

“…Beyond its influence on the cell membrane, nsPEF has been reported to induce intracellular electric stimulation, including the overload of calcium [9], phosphatidylserine translocation [10], endoplasmic reticulum stress [11], mitochondria damage [12], and other effects. The cytotoxic effect of the combination treatment of nsPEF and DOX has been proved in vitro [13,14] and in vivo [15]; however, when the exposure time of DOX is limited (10 min), nanosecond pulses with lower electric filed strength (10 kV/cm) showed poor synergic effect [14].…”