Cold Atmospheric Plasma, Created at the Tip of an Elongated Flexible Capillary Using Low Electric Current, Can Slow the Progression of Melanoma

PLoS One. 2017 Jan 19;12(1):e0169457. doi: 10.1371/journal.pone.0169457. eCollection 2017.

Abstract

Introduction: Cold Atmospheric Plasma Jet (CAPJ), with ion temperature close to room temperature, has tremendous potential in biomedical engineering, and can potentially offer a therapeutic option that allows cancer cell elimination without damaging healthy tissue. We developed a hand-held flexible device for the delivery of CAPJ to the treatment site, with a modified high-frequency pulse generator operating at a RMS voltage of <1.2 kV and gas flow in the range 0.3-3 l/min. The aims of our study were to characterize the CAPJ emitted from the device, and to evaluate its efficacy in elimination of cancer cells in-vitro and in-vivo.

Methods and results: The power delivered by CAPJ was measured on a floating or grounded copper target. The power did not drastically change over distances of 0-14 mm, and was not dependent on the targets resistance. Temperature of CAPJ-treated target was 23°-36° C, and was dependent on the voltage applied. Spectroscopy indicated that excited OH- radicals were abundant both on dry and wet targets, placed at different distances from the plasma gun. An in-vitro cell proliferation assay demonstrated that CAPJ treatment of 60 seconds resulted in significant reduction in proliferation of all cancer cell lines tested, and that CAPJ activated medium was toxic to cancer cells. In-vivo, we treated cutaneous melanoma tumors in nude mice. Tumor volume was significantly decreased in CAPJ-treated tumors relatively to controls, and high dose per fraction was more effective than low dose per fraction treatment. Importantly, pathologic examination revealed that normal skin was not harmed by CAPJ treatment.

Conclusion: This preliminary study demonstrates the efficacy of flexible CAPJ delivery system against melanoma progression both in-vitro and in-vivo. It is envisioned that adaptation of CAPJ technology for different kinds of neoplasms use may provide a new modality for the treatment of solid tumors.

MeSH terms

  • Animals
  • Biomedical Engineering / instrumentation
  • Cell Line, Tumor
  • Disease Progression
  • Equipment Design
  • Melanoma, Experimental / pathology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Plasma Gases / administration & dosage
  • Plasma Gases / therapeutic use*
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy*

Substances

  • Plasma Gases

Grants and funding

The research was funded by the MAGNET Program, in the Office of the Chief Scientist of the Ministry of Industry, Israel. Grant # 55254 and #55255; http://www.magnet.org.il/. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.