Toxicity of anticancer agents mediated by electroporation in vitro

Abstract

Electroporation is a physical event that temporarily reduces cell membrane barrier properties. Diminished membrane barrier properties are achieved by exposing cells to pulsed electric fields. When a cell has been treated with electric fields it is possible for extracellular agents to gain access to the cell interior. This process has been used in vivo to increase the uptake of chemotherapeutic agents by tumor cells which results in dramatically higher response rates than when drug is used alone. This type of treatment is called electrochemotherapy (ECT); bleomycin is most often used as the drug for this type of treatment. It was hypothesized that electroporation could be used to augment the cytotoxicity of other anticancer agents. Therefore, this study was performed in order to screen 44 different combinations of drug and cell type in vitro to identify drugs that may have higher cytotoxicity when combined with electroporation. Results from seven cell types indicate that the IC50 of bleomycin can be reduced by a factor of 100-5000 when electroporation is used to facilitate internalization. The IC50 values of cisplatin and carboplatin could be reduced by factors ranging from 3 to 13 in six different cell lines as a result of electroporation. These IC50 reductions in multiple cell lines suggest that cisplatin and carboplatin may be effective in vivo as part of ECT treatment.

Direct Therapeutic Applications of Calcium Electroporation to Effectively Induce Tumor Necrosis

“…There was a dose-dependent, dramatic decrease in viability for all electroporated cell lines with half-maximal effective concentration (EC 50 ) whereas EC 50 being 0.57 mmol/L Ca 2þ (range, 0.35-0.79 mmol/L) was not reached without electroporation. As expected, due to differences in, for example, cell size and homogeneity, there was a differential effect of the electroporation procedure alone on the different cell lines (12), as electroporation alone reduced viability by 0% (DC-3F), 6% (Lewis Lung Carcinoma), and 23% (K-562), respectively. Consequently, values are listed as a percentage of electroporated versus nonelectroporated controls, respectively.…”

PTD-mediated Loading of Tumor-Seeking Lymphocytes with Prodrug-Activating Enzymes

“…McNeil et al (36) and others (37,38) describe "scrape loading" as a means to transfer larger molecules across the cell membrane, but "scrape loading" of adherent A-NK cells with AP leads to heterogenous uptake and a significant loss of cells. Other techniques, such as red blood cell ghost fusion (39)(40)(41)(42) and electroporation (43)(44)(45)(46)(47) as a means to get enzymes across the cell membrane, also resulted in heterogeneous labeling and considerable cell loss when applied to the A-NK cells and were therefore not further pursued. In contrast, the ability of PTD to transduce A-NK cells with various molecules, such as FITC, AP, and beta-gal, was very impressive.…”

Transdermal Drug Delivery and Methods to Enhance It

“…Электрические импульсы со-здают трансмембранный потенциал в 0,5-1 В дли-тельностью 10 мкс -10 мс в зависимости от типа волны (квадратной и/или экспоненциальной), при-ложенного напряжения (50-1500 В) и интервала между импульсами (секунды или минуты). Способ электропорации сделал возможным чрескожную доставку лекарств при воспалительных заболевани-ях [49]; обезболивании [50], химиотерапии опухо-лей [51][52][53][54][55][56][57]. Кроме того, электропорация расширяет возможности генной терапии, позволяющий введе-ние ДНК, генов в клетки [58,59], а также для вак-цин [60][61][62].…”