Can We Achieve Selectivity In Plasma Medicine?

Cold physical plasmas have made a remarkable progress over the last few years and are increasingly established in clinics. Especially in chronic wound care and in palliative cancer treatment plasma has a firm foothold [1, 2]. However, the underlying mechanisms have not been completely understood [3, 4].

In the gas phase of cold plasmas, various chemical entities (electrons, ions, metastables, radicals) can be quantified which subsequently interact with an aqueous or biomolecule dominated interfacial layer. The prevailing secondary species of such encounter are matter of debate, with proposed short lived OH, 1O2, O, e-, H, medium lived NO, OCl-, O3, ONOO-, NO2-, and +/- persistent candidates NO3- or H2O2 for aqueous systems [5]. In the case of separate plasma treatment (creating plasma treated liquids) only a few species are stable enough to finally interact clinically or experimentally with a desired target [6, 7]. Similarly, in the case of the direct treatment, the resulting (or remaining) active species and their propagation in gel-like biomolecule matrices, seems to be limited to stable species. Contrasting these experimental results and conclusions, cold plasma has been deployed successfully in a number of completely different conditions. In all cases research points towards an interference with the cellular redox signaling cascade [8].

Accordingly, it must be asked if 1) a common biological denominator exist in all successful applications, if 2) the composition of the plasma treated liquid or the biomolecule matrix in direct treatment determines the effect of the plasma, if 3) the treated tissue itself determines the impact and effectivity of the treatment, or if all aspects add proportionately to the plasmas clinical effectivity. If one (or all) statements are true, it appears that i) plasma source design is subordinate, ii) selectivity is determined by the target and not the treatment, and iii) cold plasma delivers an impulse rather than a substantial dose.

To respond to these theses satisfactorily, our research applying multicellular organoid/animal models and complex biochemical models in order to seek for primary or secondary signs of redox signaling and its potential precursors or conditions [9]. Standardized protocols are used to determine the biochemical equivalence of different plasma sources and to infer on their clinical impact. It can be stated so far, that a cells or tissues properties, e.g. origin, protein content, or membrane composition, massively renders the biological impact of a plasma treatment. On the other hand, different chemical fingerprints have been obtained for various plasma sources, fueling engineering approaches to tailor selective plasma sources.