Plasma medicine—current state of research and medical application
About: This article is published in Plasma Physics and Controlled Fusion.The article was published on 2017-01-01. It has received 367 citations till now.
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307 citations
TL;DR: PAM is discussed as an anti-cancer, anti-metastatic, antimicrobial, regenerative medicine for blood coagulation and even as a dental treatment agent, and the role of PAM on cancer initiation cells, on the epithelial mesenchymal transition (EMT), and when used for metastasis inhibition considering its anticancer effects.
Abstract: Non-thermal atmospheric pressure plasma has been proposed as a new tool for various biological and medical applications. Plasma in close proximity to cell culture media or water creates reactive oxygen and nitrogen species containing solutions known as plasma-activated media (PAM) or plasma-activated water (PAW) – the latter even displays acidification. These plasma-treated solutions remain stable for several days with respect to the storage temperature. Recently, PAM and PAW have been widely studied for many biomedical applications. Here, we reviewed promising reports demonstrating plasma-liquid interaction chemistry and the application of PAM or PAW as an anti-cancer, anti-metastatic, antimicrobial, regenerative medicine for blood coagulation and even as a dental treatment agent. We also discuss the role of PAM on cancer initiation cells (spheroids or cancer stem cells), on the epithelial mesenchymal transition (EMT), and when used for metastasis inhibition considering its anticancer effects. The roles of PAW in controlling plant disease, seed decontamination, seed germination and plant growth are also considered in this review. Finally, we emphasize the future prospects of PAM, PAW or plasma-activated solutions in biomedical applications with a discussion of the mechanisms and the stability and safety issues in relation to humans.
187 citations
TL;DR: The aim of this topical review is to summarize the state of the art in plasma medicine and connect it to redox biology.
Abstract: Plasma medicine comprises the application of physical plasma directly on or in the human body for therapeutic purposes. Three most important basic plasma effects are relevant for medical applications: i) inactivation of a broad spectrum of microorganisms, including multidrug-resistant pathogens, ii) stimulation of cell proliferation and angiogenesis with lower plasma treatment intensity, and iii) inactivation of cells by initialization of cell death with higher plasma treatment intensity, above all in cancer cells. Based on own published results as well as on monitoring of relevant literature the aim of this topical review is to summarize the state of the art in plasma medicine and connect it to redox biology. One of the most important results of basic research in plasma medicine is the insight that biological plasma effects are mainly mediated via reactive oxygen and nitrogen species influencing cellular redox-regulated processes. Plasma medicine can be considered a field of applied redox biology.
166 citations
TL;DR: There is a need to highlight the main concepts distilled from plasma research in chemistry and biology that serve as a mechanistic link between plasma physics (how and which plasma-derived ROS are produced) and therapy (what is the medical benefit).
Abstract: Physical plasmas generate unique mixes of reactive oxygen and nitrogen species (RONS or ROS). Only a bit more than a decade ago, these plasmas, operating at body temperature, started to be considered for medical therapy with considerably little mechanistic redox chemistry or biomedical research existing on that topic at that time. Today, a vast body of evidence is available on physical plasma-derived ROS, from their spatiotemporal resolution in the plasma gas phase to sophisticated chemical and biochemical analysis of these species once dissolved in liquids. Data from in silico analysis dissected potential reaction pathways of plasma-derived reactive species with biological membranes, and in vitro and in vivo experiments in cell and animal disease models identified molecular mechanisms and potential therapeutic benefits of physical plasmas. In 2013, the first medical plasma systems entered the European market as class IIa devices and have proven to be a valuable resource in dermatology, especially for supporting the healing of chronic wounds. The first results in cancer patients treated with plasma are promising, too. Due to the many potentials of this blooming new field ahead, there is a need to highlight the main concepts distilled from plasma research in chemistry and biology that serve as a mechanistic link between plasma physics (how and which plasma-derived ROS are produced) and therapy (what is the medical benefit). This inevitably puts cellular membranes in focus, as these are the natural interphase between ROS produced by plasmas and translation of their chemical reactivity into distinct biological responses.
156 citations
Cites background from "Plasma medicine—current state of re..."
...ROS have been acknowledged as the main active agents responsible for the biological effects of direct and indirect plasma treatments (the latter refers to treating a liquid with plasma that is subsequently transferred to cells or tissues) [6, 11, 12]....
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TL;DR: A review focusing on atmospheric pressure plasma jets as the most studied plasma devices in plasma medicine and compiles the conditions employed to generate reactive oxygen and nitrogen species (RONS) in relevant liquids and the concentration ranges obtained.
Abstract: Reactive oxygen and nitrogen species (RONS) are among the key factors in plasma medicine. They are generated by atmospheric plasmas in biological fluids, living tissues and in a variety of liquids. This ability of plasmas to create a delicate mix of RONS in liquids has been used to design remote or indirect treatments for oncological therapy by treating biological fluids by plasmas and putting them in contact with the tumour. Documented effects include selective cancer cell toxicity, even though the exact mechanisms involved are still under investigation. However, the “right” dose for suitable therapeutical activity is crucial and still under debate. The wide variety of plasma sources hampers comparisons. This review focuses on atmospheric pressure plasma jets as the most studied plasma devices in plasma medicine and compiles the conditions employed to generate RONS in relevant liquids and the concentration ranges obtained. The concentrations of H2O2, NO2−, NO3− and short-lived oxygen species are compared critically to provide a useful overview for the reader.
137 citations
Cites background from "Plasma medicine—current state of re..."
...2 Types of plasma devices without direct electrical contact with liquids The main atmospheric plasma devices employed in medical applications are APPJ [3,4]....
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References
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TL;DR: Non-equilibrium plasmas will be shown to be non-destructive to tissue, safe, and effective in inactivation of various parasites and foreign organisms.
Abstract: An emerging field of plasma medicine is discussed, where non-equilibrium plasmas are shown to be able to initiate, promote, control, and catalyze various complex behaviors and responses in biological systems. More importantly, it will be shown that plasma can be tuned to achieve the desired medical effect, especially in medical sterilization and treatment of different kind of skin diseases. Wound healing and tissue regeneration can be achieved following various types of plasma treatment in a multitude of wound pathologies. Non-equilibrium plasmas will be shown to be non-destructive to tissue, safe, and effective in inactivation of various parasites and foreign organisms.
1,819 citations
TL;DR: The importance of ROS and RNS to plant biology has been relatively little appreciated in the plasma biomedicine community, but it appears that there are opportunities for useful applications of plasmas in this area as well.
Abstract: Reactive oxygen species (ROS) and the closely related reactive nitrogen species (RNS) are often generated in applications of atmospheric pressure plasmas intended for biomedical purposes. These species are also central players in what is sometimes referred to as ‘redox’ or oxidation‐reduction biology. Oxidation‐reduction biochemistry is fundamental to all of aerobic biology. ROS and RNS are perhaps best known as disease-associated agents, implicated in diabetes, cancer, heart and lung disease, autoimmune disease and a host of other maladies including ageing and various infectious diseases. These species are also known to play active roles in the immune systems of both animals and plants and are key signalling molecules, among many other important roles. Indeed, the latest research has shown that ROS/RNS play a much more complex and nuanced role in health and ageing than previously thought. Some of the most potentially profound therapeutic roles played by ROS and RNS in various medical interventions have emerged only in the last several years. Recent research suggests that ROS/RNS are significant and perhaps even central actors in the actions of antimicrobial and anti-parasite drugs, cancer therapies, wound healing therapies and therapies involving the cardiovascular system. Understanding the ways ROS/RNS act in established therapies may help guide future efforts in exploiting novel plasma medical therapies. The importance of ROS and RNS to plant biology has been relatively little appreciated in the plasma biomedicine community, but these species are just as important in plants. It appears that there are opportunities for useful applications of plasmas in this area as well. (Some figures may appear in colour only in the online journal)
1,218 citations
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TL;DR: The aim of the new research field of plasma medicine is the exploitation of a much more differentiated interaction of specific plasma components with specific structural as well as functional elements or functionalities of living cells.
711 citations
TL;DR: Analysis of interaction of floating electrode dielectric barrier discharge with living tissues and cells is presented and biological and physical mechanisms are discussed and a hypothesis of plasma selectivity and its effects is offered.
Abstract: Mechanisms of plasma interaction with living tissues and cells can be quite complex, owing to the complexity of both the plasma and the tissue. Thus, unification of all the mechanisms under one umbrella might not be possible. However, the authors are attempting to make first steps in this direction. In this paper, analysis of interaction of floating electrode dielectric barrier discharge (FE-DBD) with living tissues and cells is presented and biological and physical mechanisms are discussed. In physical mechanisms, charged species are identified as the major contributors to the desired effect and a mechanism of this interaction is proposed. Biological mechanisms are also addressed and a hypothesis of plasma selectivity and its effects is offered.
708 citations
TL;DR: The development of cold plasma tumour ablation has the potential of shifting the current paradigm of cancer treatment and enabling the transformation ofcancer treatment technologies by utilisation of another state of matter.
Abstract: 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. Both in-vitro and in-vivo studies revealed that cold plasmas selectively kill cancer cells. 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. 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.
655 citations