title: Electrochemotherapy by pulsed electromagnetic field treatment (PEMF) in mouse melanoma B16F10 in vivo.
abstract: BACKGROUND
  Pulsed 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.
  
  
  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 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.
  
  
  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 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Simona
authors.initials: S
authors.lastname: Kranjc
authors.affiliation: University of Ljubljana, Faculty of Electrical Engineering.
authors.forename: Matej
authors.initials: M
authors.lastname: Kranjc
authors.affiliation: Jozef Stefan Institute, Ljubljana, Slovenia.
authors.forename: Janez
authors.initials: J
authors.lastname: Scancar
authors.affiliation: Iskra Medical LLC, Ljubljana, Slovenia.
authors.forename: Jure
authors.initials: J
authors.lastname: Jelenc
authors.affiliation: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Gregor
authors.initials: G
authors.lastname: Sersa
authors.affiliation: University of Ljubljana, Faculty of Electrical Engineering.
authors.forename: Damijan
authors.initials: D
authors.lastname: Miklavcic
keywords: CDDP; bipolar pulses; contactless electroporation; electrochemotherapy; mouse melanoma; platinum determination; pulsed electromagnetic field