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

Abstract

IntroductionCold 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 ResultsThe 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.ConclusionThis 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.

Combination of Cold Atmospheric Plasma and Vitamin C Effectively Disrupts Bacterial Biofilms

“…As previously mentioned, CAP is also used for anticancer therapy [20][21][22][23]. Vitamin C has also been suggested to have adverse effects on cancer cells [28].…”

“…The unfortunate limitation in the use of CAP against tumors is that a high dose CAP exposure can also harm healthy mammalian cells [20], hence the need for precise micro devices. The recent focus in CAPanticancer treatment has thus been on developing small scale and high precision devices (micro capillaries), which led to successful inhibition of tumors [22,23].…”

Cold atmospheric pressure plasmas in dermatology: Sources, reactive agents, and therapeutic effects

“…Besides the long‐lived species in the gas phase (nitrogen oxides, ozone, and hydrogen peroxides) and UV, the fluxes of charged particles (electrons, ions, and ion clusters), strong electric field and short‐lived neutral species (O, H, N, and OH) produced by direct plasma sources can interact with the object's surface directly. [ 15,30 ] However, the fluxes of charged particles and a strong electric field may trigger minor electric shocks, especially when the direct plasma sources are used to treat wounded tissues. Therefore, skin diseases with structural integrity, such as eczema, atopic dermatitis (AD), and so forth, are the appropriate object for using direct plasma sources.…”

“…The IVIS measurement also indicated that CAP treatment decreased the melanoma penetration into the epidermal layer by 48.2%. [ 30 ] This was a very important observation and was explained by a higher susceptibility to oxidative stress due to their increased metabolic activity, a stronger effect on cells in replication and high expression of aquaporins resulting in better uptake of ROS. [ 24 ]…”

High throughput image cytometry micronucleus assay to investigate the presence or absence of mutagenic effects of cold physical plasma

“…Great efforts are currently made extending the range of plasma applications with different devices. This includes blood coagulation [Amritkar et al, 2013;Aleinik et al, 2017;Miyamoto et al, 2017], ophthalmology [Rosani et al, 2015;Ye et al, 2015;Recek et al, 2016], oncology [Ye et al, 2015;Mirpour et al, 2016;Binenbaum et al, 2017], and various diseases in dermatology [Daeschlein et al, 2010[Daeschlein et al, , 2011Klebes et al, 2014]. Addressing not only the efficacy but also safety of different plasma sources or their optimum operational settings, genotoxic testing is indispensable.…”