Cold atmospheric plasma (CAP) has shown its promising capability in cancer treatment both in vitro and in vivo . However, the anti-cancer mechanism is still largely unknown. CAP may kill cancer cells via triggering the rise of intracellular reactive oxygen species, DNA damage, mitochondrial damage, or cellular membrane damage. While the specific vulnerability of cancer cells to CAP has been observed, the underlying mechanism of such cell-based specific vulnerability to CAP is completely unknown. Here, through the comparison of CAP treatment and H 2 O 2 treatment on ten different cancer cell lines in vitro , we observed that the H 2 O 2 consumption rate by cancer cells was strongly correlated to the cytotoxicity of CAP treatment on cancer cells. Cancer cells that clear extracellular H 2 O 2 more quickly are more resistant to the cytotoxicity of CAP treatment. This finding strongly indicates that the anti-oxidant system in cancer cells play a key role in the specific vulnerability of cancer cells to CAP treatment in vitro .
The rate coefficient of an inelastic collision in plasmas can be determined by an Arrhenius-like mathematical relation. This is similar to the weights in an artificial neural network (ANN) determined by the activation functions. Therefore, a chemical pathway network (CPN) that massive chemical species are connected by the cause-effect chemical reaction pathways shares a similar mathematical ability with ANN: a functional mapping between the input space and output space. Based on such a similarity, we propose a programmable material intelligence by training a He-air plasma, considering the CPN as an ANN, to play a board game Tic-Tac-Toe. In each turn, the board information is sent to the plasma discharge units by feeding a gas combination, and the plasma returns spectra to show its next move. After training, the plasma shows a significantly high winning rate when playing against a random-move player in a 500-game test. This work thus reveals the potential of any matter that has a complicated chemical reaction system that can be used as a carrier of artificial intelligence. In other words, a material can be programmed and process data through its own molecular collisions, and thus can be considered as an analog computer at the molecular level.
Abstract Cold atmospheric plasma (CAP) technology, a relatively novel technique mainly investigated as a stand-alone cancer treatment method in vivo and in vitro, is being proposed for application in conjunction with chemotherapy. In this study, we explore whether CAP, an ionized gas produced in laboratory settings and that operates at near room temperature, can enhance Temozolomide (TMZ) cytotoxicity on a glioblastoma cell line (U87MG). Temozolomide is the first line of treatment for glioblastoma, one of the most aggressive brain tumors that remains incurable despite advancements with treatment modalities. The cellular response to a single CAP treatment followed by three treatments with TMZ was monitored with a cell viability assay. According to the cell viability results, CAP treatment successfully augmented the effect of a cytotoxic TMZ dose (50 μM) and further restored the effect of a non-cytotoxic TMZ dose (10 μM). Application of CAP in conjunction TMZ increased DNA damage measured by the phosphorylation of H2AX and induced G2/M cell cycle arrest. These findings were supported by additional data indicating reduced cell migration and increased αvβ3 and αvβ5 cell surface integrin expression as a result of combined CAP–TMZ treatment. The data presented in this study serve as evidence that CAP technology can be a suitable candidate for combination therapy with existing chemotherapeutic drugs. CAP can also be investigated in future studies for sensitizing glioblastoma cells to TMZ and other drugs available in the market.
Cold atmospheric plasma (CAP) was shown to affect cells not only directly, but also indirectly by means of plasma pre-treated solution. This study investigated a new application of CAP generated in deionized (DI) water for the cancer therapy. In our experiments, the CAP solution was generated in DI water using helium as carrier gas. We report on the effects of this plasma solution in breast (MDA-MD-231) and gastric (NCI-N87) cancer cells. The results revealed that apoptosis efficiency was dependent on the plasma exposure time and on the levels of reactive oxygen and nitrogen species (ROS and RNS). The plasma solution that resulted from 30-minute treatment of DI water had the most significant effect in the rate of apoptosis.
Pulsed arc discharges can improve arc control and tailor the ablation process in the production of 1D and 2D nanostructures from carbon anodes. In this work, low-dimensional carbon nanoparticles have been generated by means of anodic arc discharge in helium atmosphere excited with a square-wave modulated signal (1–5 Hz, 10% duty cycle). The discharges were performed between two graphite electrodes with maximal peak current of 250 A and maximal voltage of 65 V. The erosion rates and conversion efficiency of the ablated anode are compared to reference samples grown in DC steady arc mode. Ablation rates in pulsed arcs are typically of the order of 1 mg s−1. Combination of fast Langmuir probe diagnostics and optical emission spectroscopy provided plasma parameters of the discharges at the arc column. Ranges of 1016–1017 m−3 for electron density and 0.5–2.0 eV for electron temperature are estimated. The obtained samples were characterized with Raman spectroscopy and scanning electron microscopy. The deposit on the cathode after pulsed arc consisted of carbon nanostructures such as graphene nano-platelets and carbon nanotubes. Erosion dynamics of pulsed arc discharge has been described in terms of a global model and compared to steady arc discharge. A correlation is identified among discharge regimes, optical emission patterns and ablation modes. In conclusion, pulsed anodic arc discharge is a very efficient source of carbon nanomaterials. The large control of the discharge characteristics will permit to tailor accurately the production and the properties of carbon nanotubes and graphene. This deposition method is promising for the fabrication of semiconducting nanomaterials with tuneable electrical and optical properties.
Abstract This paper presents a numerical model to investigate the deformation of biological cells by applying external electric fields operating at or near cell resonant frequencies. Cells are represented as pseudo solids with high viscosity suspended in liquid media. The electric field source is an atmospheric plasma jet developed inhouse, for which the emitted energy distribution has been measured. Viscoelastic response is resolved in the entire cell structure by solving a deformation matrix assuming an isotropic material with a prescribed modulus of elasticity. To investigate cell deformation at resonant frequencies, one mode of natural cell oscillation is considered in which the cell membrane is made to radially move about its eigenfrequency. An electromagnetic wave source interacts with the cell and induces oscillation and viscoelastic response. The source carries energy in the form of a distribution function which couples a range of oscillating frequencies with electric field amplitude. Results show that cell response may be increased by the external electric field operating at or near resonance. In the elastic regime, response increases until a steady threshold value, and the structure moves as a damped oscillator. Generally, this response is a function of both frequency and magnitude of the source, with a maximum effect found at resonance. To understand the full effect of the source energy spectrum, the system is solved by considering five frequency-amplitude couplings. Results show that the total solution is a nonlinear combination of the individual solutions. Additionally, sources with different signal phases are simulated to determine the effect of initial conditions on the evolution of the system, and the result suggests that there may be multiple solutions within the same order of magnitude for elastic response and velocity. Cell rupture from electric stress may occur during application given a high energy source. Significance Cold atmospheric plasma jets (CAPJs) have been widely researched for their potential applications in cancer therapy. Existing research has focused mainly on the ability of CAPJs to deliver a mixture of reactive species which can be absorbed by cancer cells and induce cell death. The objective of our study is to investigate the mechanical effect of CAPJ electromagnetic (EM) waves on interacting cells. By coupling the EM waves associated with plasma frequency and cell viscoelastic response, we have developed a numerical tool to investigate cell damage either by mechanical or thermal loads. This work is motivated by the promise of EM waves to function as a sensitizing agent for cancer cells in preparation for chemotherapy.
The sustainable production of value-added N-heterocycles from available biomass allows to reduce the reliance on fossil resources and creates possibilities for economically and ecologically improved synthesis of fine and bulk chemicals. Herein, we present a unique Ru1CoNP/HAP surface single-atom alloy (SSAA) catalyst, which enables a new type of transformation from the bio-based platform chemical furfural to give N-heterocyclic piperidine. In the presence of NH3 and H2, the desired product is formed under mild conditions with a yield up to 93%. Kinetic studies show that the formation of piperidine proceeds via a series of reaction steps. Initially, in this cascade process, furfural amination to furfurylamine takes place, followed by hydrogenation to tetrahydrofurfurylamine (THFAM) and then ring rearrangement to piperidine. DFT calculations suggest that the Ru1CoNP SSAA structure facilitates the direct ring opening of THFAM resulting in 5-amino-1-pentanol which is quickly converted to piperidine. The value of the presented catalytic strategy is highlighted by the synthesis of an actual drug, alkylated piperidines, and pyridine. The synthesis of nitrogen-containing heterocycles from biomass is scarcely known. Here, the authors report a strategy for the N-heterocyclic piperidines synthesis by one-pot amination of the bio-based furfural utilizing a Ru1CoNP/HAP surface single-atom alloy catalyst.
Abstract Background and Significance Natural killer (NK) cells play a vital role in the human innate immune system and are being explored as a promising approach for cancer immunotherapy. Of particular interest are NK cell engagers that can target and activate NK cells to attack cancer cells. In this study, we developed novel NK cell engagers by targeting the NK cell activating receptor CD16a using antibodies that selectively distinguish between CD16a on NK cells and CD16b on granulocytes, which are highly homologous to each other. Methods and Results To generate antibodies with high developability, we employed a rational design approach to construct large yeast display libraries of human antibodies. This approach was based on the analysis of a deep sequencing dataset of human antibodies from over 500 individuals, which allowed us to determine the natural amino acid usage patterns of human antibody CDRs and mimic human antibody repertoires. Through screening these libraries, we discovered two classes of antibody clones that selectively recognize CD16a without cross-reactivity to CD16b. Epitope mapping revealed that a single amino acid difference confers over 10,000-fold selectivity for one class of antibody clones, while for the other class a second unique epitope on CD16a was identified. To evaluate the activity of these antibody clones, we produced bispecific antibody clones with one arm targeting CD16a and the other arm targeting a tumor-associated antigen (TAA). Our results demonstrated potent tumor cell-dependent activation of NK cells and effective killing of tumor cells. Several of these antibodies had greatly enhanced resistance to human IgG inhibition in killing target cells. Significantly, our anti-CD16a antibody clones exhibited superior performance compared to leading reference anti-CD16a clones in two distinct NK cell engager formats. This included higher affinity for CD16a, higher thermostability, and more potent killing activity both in the absence and presence of 10 mg/mL human IgGs as competitors. Conclusion Our findings indicate that anti-CD16a antibody-based NK cell engagers have significant potential for cancer immunotherapies.
Abstract Nowadays, a low-temperature atmospheric plasma jets are widely used in the anticancer therapy. Enhancement of electric field near the surface is one of possible ways to increase an efficiency of plasma jet treatment. Another mechanism of plasma jet’s influence on living cells is generating reactive oxygen nitrogen species (RONS). In this work effect of presence of external biased electrode was studied. Electric fields near the dielectric surface and zone of interaction were much higher than that near the conductive one due to accumulation of charge on the surface. The evolution of ionization rate near the surface was studied. It was observed experimentally and in the simulation that there are two main stages of evolution – the stage of fast ionization which is few hundreds of ns long and the stage of slow ionization with characteristic time of ∼10 µs. A 0D modelling was applied in the boundary layer near the surface in order to obtain mixture composition of RONS after several pulses.
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