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

Abstract

Introduction: Pulsed electromagnetic field (PEMF) induces pulsed electric field, which 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 methods: Noninvasive 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 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 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.

Results: The 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 growh, as well as the injection of CDDP only. The effect of the combined treatment was due to the increased cellular uptake of Pt in the tumors after the PEMF exposure, as well as its binding to DNA, as cellular target of CDDP. Approximately 2-fold increase in cellular uptake of Pt was measured.

Conclucion: The obtained results on 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.