Large volume spark discharge and plasma jet-technology for generating plasma-oxidized saline targeting colon cancer in vitro and in vivo

摘要

Cold physical plasma is a new anticancer agent. Various prototypes and a few certified devices have been developed during recent years. However, the large number of metastases disseminated into the peritoneal cavity is challenging to target directly with this emerging technology. Plasma-oxidized liquids containing tumor-toxic reactive species, in turn, are promising adjuvants in chemotherapeutic regimens. Yet, the generation of larger volumes of such liquid currently hinders its further exploration for practical application. In this study, the anticancer effect of oxidized saline generated using a spark discharge was investigated using CT26 colorectal cancer cells in vitro and in vivo and compared against oxidized saline generated by the well-investigated medical plasma jet kINPen. The reactive species deposition, as well as the storability of the liquid, was investigated. In a murine, syngeneic, orthotopic model of colorectal peritoneal carcinomatosis, the spark discharge-oxidized saline reduced the tumor burden to a lower extent when compared to the kINPen. However, and despite the lower therapeutic efficacy, the former had profound immunomodulatory effects on the levels of several peritoneal cytokines, as indicated by the marked decrease of interferon-γ, interleukin (IL)-2, IL-6, IL-10, and IL-17F. The effect observed with the kINPen on these mostly T-cell-related cytokines was less pronounced. This suggests that the spark discharge-oxidized saline unintendedly decreased the T-cell activity, presumably because of its low pH (2.7). Collectively, our results are vital in understanding the plasma-liquid-chemistry for use in oncology and will help design more optimal liquids for further exploration in research and future surgical applications.