Cold plasma selectivity and the possibility of a paradigm shift in cancer therapy

Abstract

Background: Plasma is an ionised gas that is typically generated in high-temperature laboratory conditions. However, recent progress in atmospheric plasmas has led to the creation of cold plasmas with ion temperature close to room temperature.

Methods: Both in-vitro and in-vivo studies revealed that cold plasmas selectively kill cancer cells.

Results: We show that: (a) cold plasma application selectively eradicates cancer cells in vitro without damaging normal cells; and (b) significantly reduces tumour size in vivo. It is shown that reactive oxygen species metabolism and oxidative stress responsive genes are deregulated.

Conclusion: The development of cold plasma tumour ablation has the potential of shifting the current paradigm of cancer treatment and enabling the transformation of cancer treatment technologies by utilisation of another state of matter.

Figure 1

Selectivity effect of plasma treatment: SW900 cancer cells were detached from the plate in the zone treated with plasma, whereas no detachment was observed in the treated zone for the normal NHBE cells.

Figure 2

Selectivity effect of plasma treatment: B16 melanoma cells treated with the cold plasma device for 0, 30, 60 and 120 s. (A) 24 h; (B) 48 h. Annexin V and 7-AAD staining was performed for flow cytometry analysis at 24 and 48 h after treatment. Four-quadrant analysis of the results characterises the cells as viable (unstained), apoptotic (Annexin V positive), late-apoptotic (double positive) and dead (7-AAD positive).

Figure 3

(A) Cold plasma device; (B) typical image of mice with three tumours before and after treatment (shown after 24 h); (C and D) typical image of mice with a single tumour before and approximately 1 week after treatment; (E) tumour before and immediately after the 2.5-min treatment with cold plasma jet.

Figure 4

Cold plasma treatment effect on the growth of established tumour in a murine melanoma model.

Figure 5

Cold plasma treatment effect on the mice survival in a murine melanoma model.

Figure 6

(A) A heatmap of the normalised log2 signal intensity values in the Illumina expression array for the untreated and treated sample. The colour yellow was selected to represent high log2 signal intensity values and the colour blue to represent low log2 signal intensity values. (B) MvA plot of upregulated genes (red) in a treated sample compared to an untreated sample. The values on the Y axis represent the ratio of treated/untreated log2 Fold Change. The values on the X axis represent the average log2 signal intensity. (C) MvA plot of downregulated genes (blue) in a treated sample compared to an untreated sample. The values on the Y axis represent the ratio of treated/untreated log2 Fold Change. The values on the X axis represent the average log2 signal intensity.