Current understanding of plasma-activated solutions for potential cancer therapy

Cancer therapy consists of multidisciplinary treatment combining surgery, chemotherapy, radiotherapy, and immunotherapy. Despite the elucidation of cancer mechanisms by comprehensive genomic and epigenomic analyses and the development of molecular therapy, drug resistance and severe side effects have presented challenges to the long-awaited development of new therapies. With the rapid technological advances in the last decade, there are now reports concerning potential applications of non-equilibrium atmospheric pressure plasma (NEAPP) in cancer therapy. Two approaches have been tried: direct irradiation with NEAPP (direct plasma) and the administration of a liquid (e.g. culture medium, saline, Ringer's lactate) activated by NEAPP (plasma-activated solutions: PAS). Direct plasma is a unique treatment method in which various active species, charged ions, and photons are delivered to the affected area, but the direct plasma approach has physical limitations related to the device used, such as a limited depth of reach and limited irradiation area. PAS is a liquid that contains reactive oxygen species generated by PAS, and it has been confirmed to have antitumor activity that functions in the same manner as direct plasma. This review introduces recent studies of PAS and informs researchers about the potential of PAS for cancer therapy.Potential applications of plasma-activated solutions (PAS) in cancer therapy are described.Plasma-activated species generated in PAS, its effect on tumor cells, contribution to nonmalignant immune cells, selectivity and safety are presented.The proposed anti-tumor mechanisms of PAS to date are described.Efficacy and safety evaluations of PAS have been studied in experimental animal models, but no human studies have been conducted.