Transmembrane transport and anticancer activity of strontium ranelate delivered with nanosecond pulsed electric fields (nsPEFs) into human cells in vitro

Abstract

Electropulse technology using nanosecond pulsed electric fields (nsPEFs) presents a new stimulating factor to interfere with cell functions or induce cell death in cancer cells. nsPEFs permeablilizes cells generating large numbers of non-stable nanopores in all cell membranes. This newly created pores can be efficiently used by drugs for a molecule transport in anticancer therapy. In the current research we attempted to apply nsPEF to transport strontium ranelate. Two human gastric cancer cell line (EPG85-257P and EPG85-257RDB), colon adenocarcinoma (LS-180), breast adenocarcinoma cell lines (MCF-7/WT and MCF-7/DX), melanoma (Me45), epidermal cancer (A431), normal keratinocytes (Ha-CaT) and macrophages (P388/D1) were used for nanoelectrochemotherapy in vitro. The following electrical field parameters: EP-12.5 kV/cm, 25 kV/cm, 37 kV/cm, with repetition frequency of 100 Hz, 200 impulses of 10 ns each, and time rise of 2 ns. MTT assay was applied for evaluation of combined therapy effectiveness after 24 and 72 hours. The intracellular calcium level was detected by Fluo-4, membrane permeabilization was detected by CellMask – membrane marker. The nsPEF-strontium therapy was significantly efficient in adenocarcinoma type of cells. Cells derived from skin were resistant to the applied therapy.