- Email: [email protected]
Can We Achieve Selectivity In Plasma Medicine?
Clinical Plasma Medicine 9 (2018) 2–48
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[4] H. Tanaka, K. Ishikawa, M. Mizuno, S. Toyokuni, H. Kajiyama, F. Kikkawa, H.R. Metelmann, M. Hori, State of the art in medical applications using non-thermal atmospheric pressure plasma, Rev. Mod. Plasma Phys., 1, 1: 3 (2017). [5] H. Tanaka, K. Nakamura, M. Mizuno, K. Ishikawa, K. Takeda, H. Kajiyama, F. Utsumi, F. Kikkawa, M. Hori, Non-thermal atmospheric pressure plasma activates lactate in Ringer's solution for anti-tumor effects, Sci Rep, 6, 36282 (2016). E-mail address: [email protected] (H. Tanaka). http://dx.doi.org/10.1016/j.cpme.2017.12.066
Can We Achieve Selectivity In Plasma Medicine? Kristian Wende 1, Jan-Wilm Lackmann 1, Helena Jablonowski 1, Katharina Stapelmann 2, Thomas von Woedtke 3, Sander Bekeschus 1 1
ZIK plasmatis, Leibniz Institute for Plasma Research and Technology, Greifswald, Germany Plasma for Life Sciences, North Carolina State University, 27695 Raleigh/NC, USA 3 Leibniz Institute for Plasma Research and Technology, Greifswald, Germany 2
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 þ/- 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.
Acknowledgement This work is funded by the German Federal Ministry of Education and Research (BMBF) (Grant No. 03Z22DN11&12).
References [1] [2] [3] [4] [5] [6] [7] [8] [9]
H.-R. Metelmann et al., Clinical Plasma Medicine, doi.org/10.1016/j.cpme.2017.09.001 (2017). T. von Woedtke, H. R. Metelmann, K. D. Weltmann, Contrib. Plasma Physics, 54, 104 (2014). G. Bauer and D. B. Graves, Plasma Processes and Polymers, 13, 1157 (2016). M. Keidar, D. Yan, I. I. Beilis, B. et al., Trends in Biotechnology, 2017. P. J. Bruggeman et al., Plasma Sources Science & Technology, 25, 053002 (2016). S. Bekeschus et al., Free Radic Res, 48, 542 (2014). K. Wende et al., Biointerphases, 10, 029518 (2015). A. Schmidt et al., Journal of Biological Chemistry, 14 (2015). C. Klinkhammer et al., Scientific Reports, 7, 13828 (2017).
E-mail address: [email protected] (K. Wende). http://dx.doi.org/10.1016/j.cpme.2017.12.067
43
[4] H. Tanaka, K. Ishikawa, M. Mizuno, S. Toyokuni, H. Kajiyama, F. Kikkawa, H.R. Metelmann, M. Hori, State of the art in medical applications using non-thermal atmospheric pressure plasma, Rev. Mod. Plasma Phys., 1, 1: 3 (2017). [5] H. Tanaka, K. Nakamura, M. Mizuno, K. Ishikawa, K. Takeda, H. Kajiyama, F. Utsumi, F. Kikkawa, M. Hori, Non-thermal atmospheric pressure plasma activates lactate in Ringer's solution for anti-tumor effects, Sci Rep, 6, 36282 (2016). E-mail address: [email protected] (H. Tanaka). http://dx.doi.org/10.1016/j.cpme.2017.12.066
Can We Achieve Selectivity In Plasma Medicine? Kristian Wende 1, Jan-Wilm Lackmann 1, Helena Jablonowski 1, Katharina Stapelmann 2, Thomas von Woedtke 3, Sander Bekeschus 1 1
ZIK plasmatis, Leibniz Institute for Plasma Research and Technology, Greifswald, Germany Plasma for Life Sciences, North Carolina State University, 27695 Raleigh/NC, USA 3 Leibniz Institute for Plasma Research and Technology, Greifswald, Germany 2
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 þ/- 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.
Acknowledgement This work is funded by the German Federal Ministry of Education and Research (BMBF) (Grant No. 03Z22DN11&12).
References [1] [2] [3] [4] [5] [6] [7] [8] [9]
H.-R. Metelmann et al., Clinical Plasma Medicine, doi.org/10.1016/j.cpme.2017.09.001 (2017). T. von Woedtke, H. R. Metelmann, K. D. Weltmann, Contrib. Plasma Physics, 54, 104 (2014). G. Bauer and D. B. Graves, Plasma Processes and Polymers, 13, 1157 (2016). M. Keidar, D. Yan, I. I. Beilis, B. et al., Trends in Biotechnology, 2017. P. J. Bruggeman et al., Plasma Sources Science & Technology, 25, 053002 (2016). S. Bekeschus et al., Free Radic Res, 48, 542 (2014). K. Wende et al., Biointerphases, 10, 029518 (2015). A. Schmidt et al., Journal of Biological Chemistry, 14 (2015). C. Klinkhammer et al., Scientific Reports, 7, 13828 (2017).
E-mail address: [email protected] (K. Wende). http://dx.doi.org/10.1016/j.cpme.2017.12.067