Low-temperature plasma as magic wand to differentiate between the good and the evil

Abstract

Plasma is the fourth physical state of matter, characterized by an ionized gaseous mixture, after solid, liquid, and gas phases, and contains a wide array of components such as ions, electrons, radicals, and ultraviolet ray. Whereas the sun and thunder are typical natural plasma, recent progress in the electronics enabled the generation of body-temperature plasma, designated as low-temperature plasma (LTP) or non-thermal plasma since the 1990s. LTP has attracted the attention of researchers for possible biological and medical applications. All the living species on earth utilize water as essential media for solvents and molecular transport. Thus, biological application of LTP naturally intervenes water whether LTP is exposed directly or indirectly, where plasma-activated lactate (PAL) is a standard, containing H₂O₂, NO₂⁻ and other identified molecules. Electron spin resonance and immunohistochemical studies demonstrated that LTP exposure is a handy method to load local oxidative stress. Cancer cells are characterized by persistent self-replication and high cytosolic catalytic Fe(II). Therefore, both direct exposure of LTP and PAL can provide higher damage to cancer cells in comparison to non-tumorous cells, which has been demonstrated in a variety of cancer types. The cell death mode is either apoptosis or ferroptosis, depending on the cancer-type. Thus, LTP and PAL are expected to work as an additional cancer therapy to the established guideline protocols, especially for use in somatic cavities or surgical margins.

Keywords:

• Low-temperature plasma
• oxidative stress
• cancer
• oxidative damage
• iron
• redox-active iron

Acknowledgments

YK would like to take this opportunity to thank the “Interdisciplinary Frontier Next-Generation Researcher Program of the 10 Tokai Higher Education and Research System.” The authors thank Division for Medical Research Engineering, Nagoya University Graduate School of Medicine for technical assistance.

Author contributions

ST, HZ, YK, SK, KN, HT, and YO conceived, wrote, and organized the manuscript, prepared the figures and tables, and contributed to the discussion.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported, in part, by Japan Science and Technology Agency (JST) CREST [grant number JPMJCR19H4] and Japan Society for the Promotion of Science (JSPS) Kakenhi [grant number JP19H05462], [grant number JP20H05502] to ST. JST Support for Pioneering Research Initiated by the Next Generation (SPRING) [grant number JPMJSP2125] to YK.