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Post-surgical residual tumor cells are the primary cause of relapse and progression of cancer but unfortunately, there are limited therapeutic options. In this work, a fillable plasma-activated biogel is produced on a thermosensitive biogel [(Poly-DL-lactide)-(poly-ethylene glycol)-(poly-DL-lactide), PLEL] with the aid of a discharge plasma for local post-operative treatment of cancer. In vivo data show that the plasma-activated PLEL biogel (PAPB) eliminates residual tumor tissues after removal surgery and also inhibits in situ recurrence while showing no evident systemic toxicity. Moreover, the PAPB possesses excellent storage capability, allows for slow release of plasma-generated reactive oxygen species (ROS), and exhibits good ROS-mediated anticancer effects in vitro. Our results reveal that the novel plasma-activated biogel is an effective therapeutic agent for local post-operative treatment of cancer.

Reactive oxygen and nitrogen species (ROS and RNS) generated by cold atmospheric-pressure plasma could damage genomic DNA, although the precise types of these DNA damage induced by plasma are poorly characterized. Understanding plasma-induced DNA damage will help to elucidate the biological effect of plasma and guide the application of plasma in ROS-based therapy. In this study, it was shown that ROS and RNS generated by physical plasma could efficiently induce DNA-protein crosslinks (DPCs) in bacteria, yeast, and human cells. An in vitro assay showed that plasma treatment resulted in the formation of covalent DPCs by activating proteins to crosslink with DNA. Mass spectrometry and hydroperoxide analysis detected oxidation products induced by plasma. DPC formation were alleviated by singlet oxygen scavenger, demonstrating the importance of singlet oxygen in this process. These results suggested the roles of DPC formation in DNA damage induced by plasma, which could improve the understanding of the biological effect of plasma and help to develop a new strategy in plasma-based therapy including infection and cancer therapy.

// Dehui Xu 1, 2, * , Yujing Xu 1, * , Qingjie Cui 2 , Dingxin Liu 1 , Zhijie Liu 1 , Xiaohua Wang 1 , Yanjie Yang 3 , Miaojuan Feng 4 , Rong Liang 4 , Hailan Chen 5 , Kai Ye 6, 7 and Michael G. Kong 1, 5, 8 1 State Key Laboratory of Electrical Insulation and Power Equipment, Center for Plasma Biomedicine, Xi’an Jiaotong University, Xi’an, Shaanxi, 710049, P.R. China 2 The School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi, 710049, P.R. China 3 Department of Cardiovascular Medicine, First Affiliated Hospital of the Medical School, Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, P.R. China 4 Department of Hematology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710032, P.R. China 5 Frank Reidy Center for Bioelectrics, Old Dominion University, Norfolk, VA, 23508, USA 6 School of Electronic and Information Engineering, Xi’an Jiaotong University, Xi’an, Shaanxi, 710049, P.R. China 7 First Affiliated Hospital of the Medical School, Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, P.R. China 8 Department of Electrical and Computer Engineering, Old Dominion University, Norfolk, VA, 23529, USA * These authors have contributed equally to this work Correspondence to: Michael G. Kong, email: mkong@odu.edu Kai Ye, email: ed_kaiye@mail.xjtu.edu.cn Keywords: multiple myeloma; cold atmospheric plasma; reactive oxygen species; CD95; selective inactivation Received: November 09, 2017 Accepted: January 30, 2018 Published: April 06, 2018 ABSTRACT Multiple myeloma (MM) is a fatal and incurable hematological malignancy thus new therapy need to be developed. Cold atmospheric plasma, a new technology that could generate various active species, could efficiently induce various tumor cells apoptosis. More details about the interaction of plasma and tumor cells need to be addressed before the application of gas plasma in clinical cancer treatment. In this study, we demonstrate that He+O 2 plasma could efficiently induce myeloma cell apoptosis through the activation of CD95 and downstream caspase cascades. Extracellular and intracellular reactive oxygen species (ROS) accumulation is essential for CD95-mediated cell apoptosis in response to plasma treatment. Furthermore, p53 is shown to be a key transcription factor in activating CD95 and caspase cascades. More importantly, we demonstrate that CD95 expression is higher in tumor cells than in normal cells in both MM cell lines and MM clinical samples, which suggests that CD95 could be a favorable target for plasma treatment as it could selectively inactivate myeloma tumor cells. Our results illustrate the molecular details of plasma induced myeloma cell apoptosis and it shows that gas plasma could be a potential tool for myeloma therapy in the future.

Plasma–liquid interaction has already been a hotspot in the research field of plasma medicine. Aqueous reactive oxygen species (ROS) generated in this process are widely accepted playing a crucial role in plasma biomedical effects. In this paper, chemistry pathways among various aqueous ROS induced by He + O2 plasmas are investigated by a numerical model. Simulation results show that these aqueous ROS can be classified into two groups according to their production ways: the group of species including O, 1O2 and e directly produced in plasma, and the other group of species including O2 −, H2O2, O3, etc. produced by liquid reactions. A key reaction chain of e → O2 − → HO2(→ HO2 −) → H2O2 is found to be important in the plasma-induced liquid chemistry. Furthermore, impacts of changes in plasma and solution conditions on aqueous ROS concentrations are studied as well. It is found that changes in plasma conditions (O2 ratio in the discharge gas/power density) can globally influence the concentrations of almost every aqueous ROS, while conditions changes of the treated liquid (pH/dissolved oxygen) only partially influence the concentrations of some specific species including O2 −/HO2, O3 −/HO3 and H2O2. The revelations of the liquid chemistry pathways and the dependence of ROS dosage on the treatment conditions offer a better understanding on the plasma–liquid interactions, as well as provide optimized dosage control approaches for biomedical applications.

Triple negative breast cancer (TNBC) still lacks an effective targeted treatment. In this study, hyaluronic acid (HA)-mediated tumor targeting and pH-sensitive amphiphilic polymeric nanoparticles were designed and prepared to co-deliver the anticancer drug embelin (EMB) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plasmid (pTRAIL) (EMB/TRAIL-HA/PBAE-PEI) for synergistic anti-breast cancer efficacy. These pH-sensitive amphiphilic polymeric nanoparticles were formed using the amphiphilic polymers polyethyleneimine (PEI)-poly[(1,6-hexanediol)-diacrylate-β-5-hydroxyamylamine] (PBAE), which was synthesized via Michael addition polymerization. Taking advantage of the specific binding between HA and CD44, which is highly expressed in MDA-MB-231 TNBC cells, the HA-coated nanoparticles increased drug uptake in MDA-MB-231 TNBC cells compared with MCF-7 non-TNBC cells with lower CD44 expression. Moreover, EMB/TRAIL-HA/PBAE-PEI exhibited enhanced cytotoxic and pro-apoptotic effects against MDA-MB-231 cells compared with free EMB and EMB- or pTRAIL-loaded nanoparticles via activation of caspase 3/7, an increase in reactive oxygen species levels, and inhibition of the expressions of apoptosis-related proteins. These results demonstrated that EMB/TRAIL-HA/PBAE-PEI exerted enhanced cytotoxic and pro-apoptotic effects against MDA-MB-231 cells and showed great potential for TNBC treatment.

Contamination with pathogenic and infectious viruses severely threatens human health and animal husbandry. Current methods for disinfection have different disadvantages, such as inconvenience and contamination of disinfection by-products (e.g., chlorine disinfection). In this study, atmospheric surface plasma in argon mixed with air and plasma-activated water was found to efficiently inactivate bacteriophages, and plasma-activated water still had strong antiviral activity after prolonged storage. Furthermore, it was shown that bacteriophage inactivation was associated with damage to nucleic acids and proteins by singlet oxygen. An understanding of the biological effects of plasma-based treatment is useful to inform the development of plasma into a novel disinfecting strategy with convenience and no by-product., Viruses cause serious pathogenic contamination that severely affects the environment and human health. Cold atmospheric-pressure plasma efficiently inactivates pathogenic bacteria; however, the mechanism of virus inactivation by plasma is not fully understood. In this study, surface plasma in argon mixed with 1% air and plasma-activated water was used to treat water containing bacteriophages. Both agents efficiently inactivated bacteriophages T4, Φ174, and MS2 in a time-dependent manner. Prolonged storage had marginal effects on the antiviral activity of plasma-activated water. DNA and protein analysis revealed that the reactive species generated by plasma damaged both nucleic acids and proteins, consistent with the morphological examination showing that plasma treatment caused the aggregation of bacteriophages. The inactivation of bacteriophages was alleviated by the singlet oxygen scavengers, demonstrating that singlet oxygen played a primary role in this process. Our findings provide a potentially effective disinfecting strategy to combat the environmental viruses using cold atmospheric-pressure plasma and plasma-activated water. IMPORTANCE Contamination with pathogenic and infectious viruses severely threatens human health and animal husbandry. Current methods for disinfection have different disadvantages, such as inconvenience and contamination of disinfection by-products (e.g., chlorine disinfection). In this study, atmospheric surface plasma in argon mixed with air and plasma-activated water was found to efficiently inactivate bacteriophages, and plasma-activated water still had strong antiviral activity after prolonged storage. Furthermore, it was shown that bacteriophage inactivation was associated with damage to nucleic acids and proteins by singlet oxygen. An understanding of the biological effects of plasma-based treatment is useful to inform the development of plasma into a novel disinfecting strategy with convenience and no by-product.

Summary Background Cold atmospheric plasma (CAP) has shown promise for wound healing, although little is understood of the underpinning mechanisms. Little has been reported so far of its potential use in the treatment of immune-mediated diseases such as psoriasis. Objectives To study CAP-induced cell death and cytokine release in human keratinocytes as a first assessment of possible CAP use for psoriasis. Methods Using a CAP generator free of energetic ions, we observed its effects on keratinocytes in terms of morphology, cell viability and apoptosis, intracellular and mitochondrial reactive oxygen species (ROS), lysosomal integrity and mitochondrial membrane potential; and on secretion and expression of eight cytokines at protein and gene levels. Results CAP-induced reduced cell viability, apoptotic death and production of intracellular and mitochondrial ROS in dose-dependent manner. Mitochondrial dysfunction and lysosomal leakage were found in CAP-treated cells. It also induced release of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF), and enhanced the mRNA expression of IL-1β, IL-6, IL-8, IL-10, TNF-α, interferon-γ and VEGF. By contrast, IL-12 declined monotonically. Conclusions The results suggest that with appropriate control of its dose, physical plasma could induce cell death via apoptotic pathways and enable simultaneous reduction in IL-12. These effects may be used to suppress keratinocyte hyperproliferation and to target T-cell activation to control amplification of inflammation. This provides an initial basis for further studies of CAP as a potential therapeutic option for inflammatory and immune-related diseases in dermatology, including psoriasis.

In this paper, atmospheric pressure N2/O2 plasma jets with homogeneous shielding gas excited by nanosecond pulse are obtained to generate simplex reactive nitrogen species (RNS) and reactive oxygen species (ROS), respectively, for the purpose of studying the simplex RNS and ROS to induce the myeloma cell apoptosis with the same discharge power. The results reveal that the cell death rate by the N2 plasma jet with N2 shielding gas is about two times that of the O2 plasma jet with O2 shielding gas for the equivalent treatment time. By diagnosing the reactive species of ONOO−, H2O2, OH and in medium, our findings suggest the cell death rate after plasma jets treatment has a positive correlation with the concentration of ONOO−. Therefore, the ONOO− in medium is thought to play an important role in the process of inducing myeloma cell apoptosis.

Summary form only given. This study focuses on the generation and loss of reactive oxygen species (ROS) in low-temperature atmospheric-pressure rf (13.56MHz) He+O 2 +H 2 O plasmas, which are of interest for many biomedical applications.

This study focuses on the generation and loss of reactive oxygen species (ROS) in low-temperature atmospheric-pressure RF (13.56 MHz) He + O2 + H2O plasmas, which are of interest for many biomedical applications. These plasmas create cocktails of ROS containing ozone, singlet oxygen, atomic oxygen, hydroxyl radicals, hydrogen peroxide and hydroperoxyl radicals, i.e. ROS of great significance as recognized by the free-radical biology community. By means of one-dimensional fluid simulations (61 species, 878 reactions), the key ROS and their generation and loss mechanisms are identified as a function of the oxygen and water content in the feed gas. Identification of the main chemical pathways can guide the optimization of He + O2 + H2O plasmas for the production of particular ROS. It is found that for a given oxygen concentration, the presence of water in the feed gas decreases the net production of oxygen-derived ROS, while for a given water concentration, the presence of oxygen enhances the net production of water-derived ROS. Although most ROS can be generated in a wide range of oxygen and water admixtures, the chemical pathways leading to their generation change significantly as a function of the feed gas composition. Therefore, care must be taken when selecting reduced chemical sets to study these plasmas.

Plasma-liquid interaction is a critical area of plasma science and a knowledge bottleneck for many promising applications. In this paper, the interaction between a surface air discharge and its downstream sample of deionized water is studied with a system-level computational model, which has previously reached good agreement with experimental results. Our computational results reveal that the plasma-induced aqueous species are mainly H+, nitrate, nitrite, H2O2 and O3. In addition, various short-lived aqueous species are also induced, regardless whether they are generated in the gas phase first. The production/loss pathways for aqueous species are quantified for an air gap width ranging from 0.1 to 2 cm, of which heterogeneous mass transfer and liquid chemistry are found to play a dominant role. The short-lived reactive oxygen species (ROS) and reactive nitrogen species (RNS) are strongly coupled in liquid-phase reactions: NO3 is an important precursor for short-lived ROS, and in turn OH, O2− and HO2 play a crucial role for the production of short-lived RNS. Also, heterogeneous mass transfer depends strongly on the air gap width, resulting in two distinct scenarios separated by a critical air gap of 0.5 cm. The liquid chemistry is significantly different in these two scenarios.