Electrochemotherapy by pulsed electromagnetic field treatment (PEMF) in mouse melanoma B16F10 in vivo

Abstract

IntroductionPulsed electromagnetic field (PEMF) induces pulsed electric field, which presumably increases membrane permeabilization of the exposed cells, similar to the conventional electroporation. Thus, contactless PEMF could represent a promising approach for drug delivery.Materials and methodsNoninvasive electroporation was performed by magnetic field pulse generator connected to an applicator consisting of round coil. Subcutaneous mouse B16F10 melanoma tumors were treated with intravenously injection of cisplatin (CDDP) (4 mg/kg), PEMF (480 bipolar pulses, at frequency of 80 Hz, pulse duration of 340 μs) or with the combination of both therapies (electrochemotherapy − PEMF + CDDP). Antitumor effectiveness of treatments was evaluated by tumor growth delay assay. In addition, the platinum (Pt) uptake in tumors and serum, as well as Pt bound to the DNA in the cells and Pt in the extracellular fraction were measured by inductively coupled plasma mass spectrometry.ResultsThe antitumor effectiveness of electrochemotherapy with CDDP mediated by PEMF was comparable to the conventional electrochemotherapy with CDDP, with the induction of 2.3 days and 3.0 days tumor growth delay, respectively. The exposure of tumors to PEMF only, had no effect on tumor growth, as well as the injection of CDDP only. The antitumor effect in combined treatment was related to increased drug uptake into the electroporated tumor cells, demonstrated by increased amount of Pt bound to the DNA. Approximately 2-fold increase in cellular uptake of Pt was measured.ConclusionsThe obtained results in mouse melanoma model in vivo demonstrate the possible use of PEMF induced electroporation for biomedical applications, such as electrochemotherapy. The main advantages of electroporation mediated by PEMF are contactless and painless application, as well as effective electroporation compared to conventional electroporation.

Design and Optimization of Pulsed Magnetic Field Generator for Cell Magneto-Permeabilization

“…As it can be seen in Fig. 2 (bottom) the induced electric field value is in the range of 3.5 kV/m, which is sufficient for magneto-permeabilization studies [12].…”

“…Biological effects of pulsed magnetic field (PMF) are pulse dependent [12], [13], therefore in this case the biological phenomenon (magnetoporation) determines and raises the requirements for a pulsed system that is needed for research. At the current state of knowledge, it is believed that the PMF permeabilization phenomenon is triggered by means of contactless induction of voltage on the cell membrane, causing electroporation [5], [12], [13]. Nevertheless, the dose-dependent pulsed magnetic field…”

Pulsed Electromagnetic Field Stimulation Promotes Anti-cell Proliferative Activity in Doxorubicin-treated Mouse Osteosarcoma Cells

“…In conclusion, a recent report showed that a combination of cisplatin and PEMF inhibited the growth of mouse melanoma B16F10 cells (35), while another study reported that PEMF protected puromycin-induced U937 cell death, depending on cell density (36). Although reports on combined anticancer drug and PEMF therapies are scarce, a combination of PEMF and doxorubicin appears to affect osteosarcoma cells.…”

Electrotransfer of siRNA to Silence Enhanced Green Fluorescent Protein in Tumor Mediated by a High Intensity Pulsed Electromagnetic Field

“…We have already shown that small molecules can be delivered with HI-PEMF in vitro [26] and in vivo [29]. Few studies have evaluated the mechanisms of molecule uptake after the exposure of cells to HI-PEMF.…”

“…High intensity pulsed electromagnetic fields (HI-PEMF) were also demonstrated to increase transmembrane molecular transport, presumably through the successful electroporation of the cell membrane [25,26]. Furthermore, HI-PEMFs were successfully used for drug and plasmid DNA delivery in vitro and in vivo [27][28][29]. Thus, HI-PEMF has the potential for achieving cell and tissue electroporation in a noncontact manner.…”