The cell membrane can be permeabilized when subjected to calibrated short electric pulses. This membrane alteration can be reversible, leaving cell viability unaffected. This set of events is called electroporation (EP). It is now used in clinical applications to introduce hydrophilic drugs into the cytoplasm. One of the EP applications is electrochemotherapy (ECT), in which EP is used for the selective delivery of drugs administered to treat cancer. The combination of EP with chemotherapy allows local cancer treatment, lowering the drug dose and reducing the side effects of systemic chemotherapy. Nowadays, bleomycin-based ECT (BLM-ECT) is a safe treatment for cutaneous tumors and skin metastases with established standard operating procedures. Additionally, there is emerging evidence that BLM-ECT may be particularly effective in combination with immunotherapies, acting synergistically and producing enhanced systemic anti-tumor effects. Still, to make it the first-choice therapy in patients with metastatic melanoma, further studies are needed to establish the relative effectiveness of ECT. Analyzing the EP phenomenon and the objective complexity of the associated effects at the cell level, we came across a problem that has not yet been investigated in increasing the therapeutic effectiveness of ECT. The profile and kinetics of extracellular vesicles (EVs) released from cells subjected to EP have not been analyzed. The exact nature of these EVs is unknown.
Keywords: electrochemotherapy; electroporation; extracellular vesicles; melanoma.