Stabilizing the cold plasma-stimulated medium by regulating medium’s composition

Abstract

Over past several years, the cold plasma-stimulated medium (PSM) has shown its remarkable anti-cancer capacity in par with the direct cold plasma irradiation on cancer cells or tumor tissues. Independent of the cold plasma device, PSM has noticeable advantage of being a flexible platform in cancer treatment. Currently, the largest disadvantage of PSM is its degradation during the storage over a wide temperature range. So far, to stabilize PSM, it must be remained frozen at −80 °C. In this study, we first reveal that the degradation of PSM is mainly due to the reaction between the reactive species and specific amino acids; mainly cysteine and methionine in medium. Based on this finding, both H2O2 in PSM and the anti-cancer capacity of PSM can be significantly stabilized during the storage at 8 °C and −25 °C for at least 3 days by using phosphate-buffered saline (PBS) and cysteine/methionine-free Dulbecco’s Modified Eagle Medium (DMEM). In addition, we demonstrate that adding a tyrosine derivative, 3-Nitro-L-tyrosine, into DMEM can mitigate the degradation of PSM at 8 °C during 3 days of storage. This study provides a solid foundation for the future anti-cancer application of PSM.

Non-thermal atmospheric pressure plasma activates lactate in Ringer’s solution for anti-tumor effects

“…H 2 O 2 is an anti-tumor factor that is typically generated in solutions by plasma treatment475760. To investigate whether H 2 O 2 generated in PAL is responsible for the observed anti-tumor effects, we measured the H 2 O 2 concentrations of these solutions (Fig.…”

“…Cold plasma affects biological targets not only directly but also indirectly through the medium, which has broadened the potential applications of non-thermal atmospheric pressure plasma in medicine41424344454647484950. We have demonstrated that plasma-irradiated medium, also called plasma-activated medium (PAM), has anti-tumor effects against glioblastoma5152, as well as ovarian5354, gastric55, pancreatic56, and lung cancer cells57.…”

“…In addition to these species that are generally produced by plasma irradiation of liquid, specific species that vary depending on the solution are important for anti-tumor effects. Plasma-activated solutions with simple compositions, such as phosphate-buffered saline (PBS), might be better for treating cancer than more complex solutions47. However, the exact species responsible for the anti-tumor effects remain unclear.…”

Aqueous Plasma Pharmacy: Preparation Methods, Chemistry, and Therapeutic Applications

“…Follow-up work identified methionine in addition to cysteine as medium-containing amino acids that scavenged plasma species most effectively. 67 …”

State of the art in medical applications using non-thermal atmospheric pressure plasma

“…Another approach is PAM, which is broadly defined as medium or solution following exposure to plasma (Tanaka et al , 2014b(Tanaka et al , 2015a2016a). PAM selectively kills cancer cells and induces apoptosis, as demonstrated independently by researchers worldwide (Yan et al 2014;Mohades et al 2015;Judee et al 2016;Kumar et al 2016;Yan et al 2016).…”