The Biophysics of Cold Plasmas in Cancer Therapy

低温大气压等离子体在室温下引发高度反应性化学反应，能够影响敏感的生物系统。例如，等离子体引发的肿瘤消退的发现显示了冷等离子体在癌症治疗中的潜力。到目前为止，等离子体与生物体的各种相互作用过程非常不清楚，甚至完全不了解。BioCaT计划的目的是通过使用生物物理和聚合物模型系统作为活组织的模型系统来揭示和定制等离子体反应性的影响。利用一种新颖的基于物理的方法，BioCaT将首次在等离子体-生物相互作用中定制等离子体反应性。我们的方法的动机是最近的氧化还原生物学研究表明亚稳态单线态氧在选择性癌细胞死亡中的重要性：单线态氧使细胞膜相关酶失活，导致雪崩样过程导致细胞死亡。o2是空气中冷等离子体的关键成分。BioCaT将揭示等离子体-液体系统中的基本动力学过程，以控制组成反应物质的组成：目前的经验性等离子体应用需要被基于知识的靶向等离子体反应性所取代。在新的诊断概念下，反应物质在空间和时间上的密度梯度将在气相、等离子体和液相中测定。将定量单次射击技术应用于冷等离子体的湍流反应流动，将首次允许人们识别瞬态反应动力学。将采用基于反应动力学模型的方法，以便具体影响导致1O2产生和传输的物理参数到介导等离子体效应的液体界面。第一次，血浆对酶活性的影响将被研究的酶将被空间固定在一个聚合物基质或脂质体细胞模型。这将使我们了解等离子体在生物体中的作用过程，例如，它是如何影响人体细胞的。因此，BioCaT将与一个跨学科的研究团队一起，建立定制冷大气压等离子体用于选择性细胞治疗所需的知识库。预计该研究成果将在等离子体医学研究方面取得突破，并为低温大气压等离子体的成功临床应用开辟道路。

Cold atmospheric pressure plasmas initiate highly reactive chemistry at room temperature, able to influence sensitive biological systems. For example, findings of plasma-initiated tumor regression show the potential of cold plasmas in cancer care. Until now, the various interaction processes of plasma with living organisms are very poorly to not at all understood. The aim of this proposed program, BioCaT, is to reveal and tailor the effect of plasma reactivity by using biophysical and polymeric model systems as model systems for living tissue. With a novel physics-based approach, BioCaT will for the first time tailor the plasma reactivity in plasma-bio-interaction. Motivation for our approach are recent redox biology studies that show the importance of metastable singlet oxygen 1O2 in selective cancer cell death: Singlet oxygen inactivates cell membrane-associated enzymes, leading to avalanche-like processes that result in cell death. 1O2 is a key component of cold plasmas in air. BioCaT will reveal the fundamental kinetic processes in plasma-liquid-systems to control the composition of constituent reactive species: Current empirical plasma application needs to be replaced by knowledge-based, targeted plasma reactivity. With new diagnostic concepts, density gradients of reactive species in space and time will be determined in gas-, plasma- and liquid-phases. Applying quantitative single-shot techniques to turbulent reactive flow of cold plasmas will, for the first time, allow one to identify transient reaction kinetics. The reaction kinetics model-based approach will be adapted so as to specifically influence those physical parameters that lead to generation and transport of 1O2, to the liquid interface that mediates the plasma effect. For the first time, the effect of plasma on enzyme activity will be studied on hand of enzymes that will be spatially immobilized by a polymer matrix or by liposome cell models. This will allow us to understand the progression of plasma effects in living organisms, for example, how it affects human cells. With an interdisciplinary researcher team, BioCaT will thus build the knowledge-base required to tailor cold atmospheric pressure plasmas for selective cell treatment. The research results are anticipated to yield breakthroughs in plasma-medical research and to open the way for successful clinical use of cold atmospheric pressure plasmas.