The role of short- and long-lived reactive species on the anti-cancer action of plasma-treated liquids: in vitro and in vivo applications

In this study, we investigated two modes of plasma cancer treatment (direct vs indirect) and unveiled the role of different reactive oxygen and nitrogen species (RONS) on the selective nature and anti-cancer action of plasma-treated PBS (pPBS). In vitro, we used 2 models of cancer cells and 3 normal cell lines [1]. We observed a selective anti-cancer action of the indirect plasma treatment and an anti-selective action of the direct plasma treatment. We demonstrated that the hypersensitivity of normal cells to direct plasma treatment cannot be explained only by the action of long-lived RONS, but it also requires the participation of short/intermediate-lived RONS [1]. Considering the selective nature of the indirect plasma treatment, we decided to use pPBS as an anti-cancer drug both in vitro and in vivo in combination with electrochemotherapy (ECT). We showed in vitro that the combined treatment opens the possibility to reduce the amplitude of the microsecond-pulsed electric fields (µsPEFs), allowing an ECT treatment with reduced side-effects. Finally, we observed in vivo on mice that the combination of pPBS and µsPEFs delays the tumour growth and increases the probability of survival compared to µsPEFs or ECT treatments alone.