Novel plasma-based technologies that offer maximum efficiency at minimal environmental costs are expected to further promote the sustainable societal and economic development. Unique transfer of chemical reactivity and energy from gaseous plasmas to water takes place in the absence of any other chemicals, but results in a product with a notable transient broad-spectrum biological activity, referred to as plasma-activated water (PAW). These features make PAW a green prospective solution for a wide range of biotechnology applications, from water purification to biomedicine. Here, we present a succinct review of how novel, efficient methods based on non-equilibrium reactive plasma chemistries can be applied to low-cost natural water sources to produce a prospective product with a wide range of applications while at the same time minimising the process steps and dramatically reducing the use of expensive and/or hazardous reagents. Despite the recent exciting developments in this field, there presently is no topical review which specifically focuses on the underlying physics and chemistry related to plasma-activated water. We focus specifically on the PAW generation, origin of reactive species present in PAW, its related analytical chemistry and potentially different mechanisms that regulate the bio-activities of PAW in different biotech-applications and their roles in determining PAW efficacy and selectivity. We then review recent advances in our understanding of plasma-water interactions, briefly outlining current and proposed applications of PAW in agriculture, food and biomedicine. Finally, we outline future research directions and challenges that may hinder translation of these technologies into real-life applications. Overall, this review will provide much needed insights into the fundamental aspects of PAW chemistry required for optimization of the biochemical activity of PAW and translation of this environment- and human-health-friendly, and energy-efficient strategy into real life applications.

Tumor cells demonstrate substantial plasticity in their genotypic and phenotypic characteristics. Epithelial-mesenchymal plasticity (EMP) can be characterized into dynamic intermediate states and can be orchestrated by many factors, either intercellularly via epigenetic reprograming, or extracellularly via growth factors, inflammation and/or hypoxia generated by the tumor stromal microenvironment. EMP has the capability to alter phenotype and produce heterogeneity, and thus by changing the whole cancer landscape can attenuate oncogenic signaling networks, invoke anti-apoptotic features, defend against chemotherapeutics and reprogram angiogenic and immune recognition functions. We discuss here the role of phenotypic plasticity in tumor initiation, progression and metastasis and provide an update of the modalities utilized for the molecular characterization of the EMT states and attributes of cellular behavior, including cellular metabolism, in the context of EMP. We also summarize recent findings in dynamic EMP studies that provide new insights into the phenotypic plasticity of EMP flux in cancer and propose therapeutic strategies to impede the metastatic outgrowth of phenotypically heterogeneous tumors.

Cold atmospheric plasma (CAP) has emerged as a highly selective anticancer agent, most recently in the form of plasma-activated medium (PAM). Since epithelial–mesenchymal transition (EMT) has been implicated in resistance to various cancer therapies, we assessed whether EMT status is associated with PAM response. Mesenchymal breast cancer cell lines, as well as the mesenchymal variant in an isogenic EMT/MET human breast cancer cell system (PMC42-ET/LA), were more sensitive to PAM treatment than their epithelial counterparts, contrary to their responses to other therapies. The same trend was seen in luminal muscle-invasive bladder cancer model (TSU-Pr1/B1/B2) and the non-muscle-invasive basal 5637 bladder cancer cell line. Three-dimensional spheroid cultures of the bladder cancer cell lines were less sensitive to the PAM treatment compared to their two-dimensional counterparts; however, incrementally better responses were again seen in more mesenchymally-shifted cell lines. This study provides evidence that PAM preferentially inhibits mesenchymally-shifted carcinoma cells, which have been associated with resistance to other therapies. Thus, PAM may represent a novel treatment that can selectively inhibit triple-negative breast cancers and a subset of aggressive bladder cancers, which tend to be more mesenchymal. Our approach may potentially be utilized for other aggressive cancers exhibiting EMT and opens new opportunities for CAP and PAM as a promising new onco-therapy.