Cell Membrane Oscillations under Radiofrequency Electromagnetic Modulation.

Cell responses to external radiofrequencies (RF) are a fundamental problem of much scientific research, clinical applications, and even daily lives surrounded by wireless communication hardware. In this work, we report an unexpected observation that the cell membrane can oscillate at the nanometer scale in phase with the external RF radiation from kHz to GHz. By analyzing the oscillation modes, we reveal the mechanism behind the membrane oscillation resonance, membrane blebbing, the resulting cell death, and the selectivity of plasma-based cancer treatment based on the difference in the membrane's natural frequencies among cell lines. Therefore, a selectivity of treatment can be achieved by aiming at the natural frequency of the target cell line to focus the membrane damage on the cancer cells and avoid normal tissues nearby. This gives a promising cancer therapy that is especially effective in the mixing lesion of the cancer cells and normal cells such as glioblastoma where surgical removal is not applicable. Along with these new phenomena, this work provides a general understanding of the cell coupling with RF radiation from the externally stimulated membrane behavior to the cell apoptosis and necrosis.

Replenishment of the Gas in a Hydrophobically-Structured Surface by Mass Transfer at the Liquid-Gas Interface for Improving the Stability of Entrapped Gas.

The underwater nonwetted state on a superhydrophobic surface is hardly maintained in flowing water because the entrapped gas dissolves into the water or is carried off by flow. Therefore, a source gas is necessary to maintain a superhydrophobic state for its applications under realistic conditions. As detailed in this paper, based on the gas entrapped on a hydrophobic structured surface, the gas regeneration was experimentally achieved to replenish the losses of gas carried off by the flowing and reduced through dissolution. Furthermore, the mechanism of mass transfer at the liquid-gas interface was investigated by simulation. The results indicated that water molecules at a liquid-gas interface should escape to entrapped gas when water content didn't reach saturation. This phenomenon could be due to the evaporation at the liquid-gas interface. With the increasing water content in the entrapped gas, the evaporation rate at the liquid-gas interface descended gradually. Under the action of flowing, the substances containing high concentrations of water molecule was washed away at the liquid-gas interface. Therefore, the low concentration of the water molecule at the liquid-gas interface was created. As a result, the equilibrium of water and gas at the liquid-gad interface was broken, and the evaporation continued to replenish the lost gas. Overall, the presented results in this study could be considered a promising candidate for replenishing the lost gas in hydrophobic structured surfaces by mass transfer at the liquid-gas interface.

Preclinical Cold Atmospheric Plasma Cancer Treatment.

CAP is an ionized gas generated under atmospheric pressure conditions. Due to its reactive chemical components and near-room temperature nature, CAP has promising applications in diverse branches of medicine, including microorganism sterilization, biofilm inactivation, wound healing, and cancer therapy. Currently, hundreds of in vitro demonstrations of CAP-based cancer treatments have been reported. However, preclinical studies, particularly in vivo studies, are pivotal to achieving a final clinical application. Here, we comprehensively introduced the research status of the preclinical usage of CAP in cancer treatment, by primarily focusing on the in vivo studies over the past decade. We summarized the primary research strategies in preclinical and clinical studies, including transdermal CAP treatment, post-surgical CAP treatment, CAP-activated solutions treatment, and sensitization treatment to drugs. Finally, the underlying mechanism was discussed based on the latest understanding.

Wettability Improvement in Oil-Water Separation by Nano-Pillar ZnO Texturing.

The nanostructure-based surface texturing can be used to improve the materials wettability. Regarding oil−water separation, designing a surface with special wettability is as an important approach to improve the separation efficiency. Herein, a ZnO nanostructure was prepared by a two-step process for sol−gel process and crystal growth from the liquid phase to achieve both a superhydrophobicity in oil and a superoleophobic property in water. It is found that the filter material with nanostructures presented an excellent wettability. ZnO-coated stainless-steel metal fiber felt had a static underwater oil contact angle of 151.4° ± 0.8° and an underoil water contact angle of 152.7° ± 0.6°. Furthermore, to achieve water/oil separation, the emulsified impurities in both water-in-oil and oil-in-water emulsion were effectively intercepted. Our filter materials with a small pore (~5 µm diameter) could separate diverse water-in-oil and oil-in-water emulsions with a high efficiency (>98%). Finally, the efficacy of filtering quantity on separation performance was also investigated. Our preliminary results showed that the filtration flux decreased with the collection of emulsified impurities. However, the filtration flux could restore after cleaning and drying, suggesting the recyclable nature of our method. Our nanostructured filter material is a promising candidate for both water-in-oil and oil-in-water separation in industry.

Cold Plasma Discharge Tube Enhances Antitumoral Efficacy of Temozolomide.

Glioblastoma (GBM) is a fatal human brain tumor with a low survival rate. Temozolomide (TMZ) has been widely used in GBM therapy with noticeable side effects. Cold plasma is an ionized gas that is generated near room temperature. Here, we demonstrated the enhancement therapeutic efficacy of TMZ via using a cold plasma source based on nonequilibrium plasma in a sealed glass tube, named a radial cold plasma discharge tube (PDT). The PDT affected glioblastoma cells' function just by its electromagnetic (EM) emission rather than any chemical factors in the plasma. The PDT selectively increased the cytotoxicity of TMZ on two typical glioblastoma cell lines, U87MG and A172, compared with normal astrocyte cell line hTERT/E6/E7 to some extent. Furthermore, on the basis of a patient-derived xenograft model, our preliminary in vivo studies demonstrated the drastically improved mean survival days of the tumor-barrier mice by more than 100% compared to control. The PDT is not only independent of continuous helium supply but is also capable of resisting the interference of environmental changes. Thus, the PDT was a stable and low-cost cold atmospheric plasma source. In short, this study is the first to demonstrate the promising application of PDTs in GBM therapy as a noninvasive and portable modality.

Anti-Melanoma Capability of Contactless Cold Atmospheric Plasma Treatment.

In this study, we demonstrated that the widely used cold atmospheric plasma (CAP) jet could significantly inhibit the growth of melanoma cells using a contactless treatment method, The flow rate of helium gas was a key operational parameter to modulate electromagnetic (EM) effect on melanoma cells. Metal sheets with different sizes could be used as a strategy to control the strength of EM effect. More attractive, the EM effect from CAP could penetrate glass/polystyrene barriers as thick as 7 mm. All these discoveries presented the profound non-invasive nature of a physically based CAP treatment, which provided a solid foundation for CAP-based cutaneous/subcutaneous tumor therapy.

Multi-Modal Biological Destruction by Cold Atmospheric Plasma: Capability and Mechanism.

Cold atmospheric plasma (CAP) is a near-room-temperature, partially ionized gas composed of reactive neutral and charged species. CAP also generates physical factors, including ultraviolet (UV) radiation and thermal and electromagnetic (EM) effects. Studies over the past decade demonstrated that CAP could effectively induce death in a wide range of cell types, from mammalian to bacterial cells. Viruses can also be inactivated by a CAP treatment. The CAP-triggered cell-death types mainly include apoptosis, necrosis, and autophagy-associated cell death. Cell death and virus inactivation triggered by CAP are the foundation of the emerging medical applications of CAP, including cancer therapy, sterilization, and wound healing. Here, we systematically analyze the entire picture of multi-modal biological destruction by CAP treatment and their underlying mechanisms based on the latest discoveries particularly the physical effects on cancer cells.

Plasma-Treated Solutions (PTS) in Cancer Therapy.

Cold physical plasma is a partially ionized gas generating various reactive oxygen and nitrogen species (ROS/RNS) simultaneously. ROS/RNS have therapeutic effects when applied to cells and tissues either directly from the plasma or via exposure to solutions that have been treated beforehand using plasma processes. This review addresses the challenges and opportunities of plasma-treated solutions (PTSs) for cancer treatment. These PTSs include plasma-treated cell culture media in experimental research as well as clinically approved solutions such as saline and Ringer's lactate, which, in principle, already qualify for testing in therapeutic settings. Several types of cancers were found to succumb to the toxic action of PTSs, suggesting a broad mechanism of action based on the tumor-toxic activity of ROS/RNS stored in these solutions. Moreover, it is indicated that the PTS has immuno-stimulatory properties. Two different routes of application are currently envisaged in the clinical setting. One is direct injection into the bulk tumor, and the other is lavage in patients suffering from peritoneal carcinomatosis adjuvant to standard chemotherapy. While many promising results have been achieved so far, several obstacles, such as the standardized generation of large volumes of sterile PTS, remain to be addressed.

The anti-glioblastoma effect of cold atmospheric plasma treatment: physical pathway v.s. chemical pathway.

Cold atmospheric plasma (CAP), a near room temperature ionized gas, has shown potential application in many branches of medicine, particularly in cancer treatment. In previous studies, the biological effect of CAP on cancer cells and other mammalian cells has been based solely on the chemical factors in CAP, particularly the reactive species. Therefore, plasma medicine has been regarded as a reactive species-based medicine, and the physical factors in CAP such as the thermal effect, ultraviolet irradiation, and electromagnetic effect have been regarded as ignorable factors. In this study, we investigated the effect of a physical CAP treatment on glioblastoma cells. For the first time, we demonstrated that the physical factors in CAP could reinstate the positive selectivity on CAP-treated astrocytes. The positive selectivity was a result of necrosis, a new cell death in glioblastoma cells characterized by the leak of bulk water from the cell membrane. The physically-based CAP treatment overcomed a large limitation of the traditional chemically based CAP treatment, which had complete dependence on the sensitivity of cells to reactive species. The physically-based CAP treatment is a potential non-invasive anti-tumor tool, which may have wide application for tumors located in deeper tissues.

A Physically Triggered Cell Death via Transbarrier Cold Atmospheric Plasma Cancer Treatment.

Cold atmospheric plasma (CAP) is a near room-temperature ionized gas composed of highly reactive species. CAP also generates thermal radiation, ultraviolet radiation, and electromagnetic (EM) waves. So far, nearly all biological effects of CAP have relied on the chemical factors in CAP. Here, we first show that the EM emission from CAP can lead to the death of melanoma cells via a transbarrier contactless method. Compared with reactive species, the effect of the physical factors causes much stronger growth inhibition on a reactive species-resistant melanoma cell line B16F10. Such a physically triggered growth inhibition is due to a new cell death type, characterized by the rapid leakage of bulk solutions from the cells, resulting in cytoplasm shrinkage and bubbling on the cell membrane. The physically based CAP-triggered cell death can occur even there is a macroscale gap between the bulk CAP and cells, which includes an air gap (∼8 mm) and a dielectric material of the dish or plate (∼1 mm). Either a too large or a too small gap will inhibit such cell death. The physically triggered cellular pressure may cause the bubbling on cells, which can be inhibited in a hypotonic environment via the extracellular osmotic pressure. This study builds a foundation to use CAP as a physically based noninvasive cancer treatment.

Integrating cold atmospheric plasma with 3D printed bioactive nanocomposite scaffold for cartilage regeneration.

The progressive degeneration of articular cartilage or osteoarthritis of the knee is a serious clinical problem affecting patient quality of life. In recent years, artificially engineered cartilage scaffolds have been widely studied as a promising method to stimulate cartilage regeneration. In this study, a novel biomimetic cartilage scaffold was developed by integrating a cold atmospheric plasma (CAP) treatment with prolonged release of bioactive factors. Specifically, a surface of 3D printed hydrogel scaffold with drug-loaded nanoparticles was treated with CAP. Our results showed that the scaffolds with CAP treatment can improve hydrophilicity as well as surface nano-roughness and can thus facilitate stem cell adhesion. More importantly, this study demonstrated that integrating CAP treatment with drug-loaded nanoparticles can synergistically enhance chondrogenesis of human bone marrow mesenchymal stem cells when compared to control scaffolds. The results in this study indicate the great potential of applying CAP and drug-loaded nanoparticles into 3D printed tissue scaffolds for promoting cartilage regeneration.

Cold Atmospheric Plasma as a Novel Therapeutic Tool for the Treatment of Brain Cancer.

BACKGROUND: Studies from the past few years revealed the importance of Cold Atmospheric Plasma (CAP) on various kinds of diseases, including brain cancers or glioblastoma (GBM), and hence coined a new term 'Plasma Medicine' in the modern world for promising therapeutic approaches. Here, we focus on the efficacy of CAP and its liquid derivatives on direct interactions or with specific nanoparticles to show pivotal roles in brain cancer treatment. METHOD: In the present review study, the authors studied several articles over the past decades published on the types of CAP and its effects on different brain cancers and therapy. RESULTS: A growing body of evidence indicates that CAP and its derivatives like Plasma Activated Media/ Water (PAM/PAW) are introduced in different kinds of GBM. Recent studies proposed that CAP plays a remarkable role in GBM treatment. To increase the efficacy of CAP, various nanoparticles of different origins got specific attention in recent times. In this review, different strategies to treat brain cancers, including nanoparticles, are discussed as enhancers of CAP induced targeted nanotherapeutic approach. CONCLUSION: CAP treatment and its synergistic effects with different nanoparticles hold great promise for clinical applications in early diagnosis and treatment of GBM treatment. However, results obtained from previous studies were still in the preliminary phase, and there must be a concern over the use of optimal methods for a dosage of CAP and nanoparticles for complete cure of GBM.

Atmospheric Plasma Meets Cell: Plasma Tailoring by Living Cells.

The applications of the cold atmospheric plasma jet (CAPJ) in cancer treatment have been investigated for over a decade, focused on the effect that the CAPJ creates on cancer cells. Here we report for the first time on the impact that cells have on the CAPJ during treatment. To better understand these CAPJ-cell interactions, we analyzed the CAPJ behaviors in the presence of several normal and cancer cell lines and investigated the CAPJ selectivity. A more in-depth study of plasma self-organization patterns utilizing a model which contains a combination of normal and cancer cells reveals that the cells' capacitance can be an important predictor of plasma jet behavior. Cancer cells can direct the jet either toward or away from normal cells, which depends on the boundary condition behind the cell colony. Both experimental and theoretical results show that a grounded copper board beneath the cell-culture dish leads to opposite CPAJ behaviors compared with a floating boundary condition. In conclusion, our findings indicate that plasma can be self-adaptive toward cancer cells, and such a feature can be manipulated. Therefore, using the permittivity difference among cell lines may help us focus plasmas upon cancer cells at the vicinity of normal tissues and maximize the selectivity of plasma treatments.

The Cell Activation Phenomena in the Cold Atmospheric Plasma Cancer Treatment.

Cold Atmospheric Plasma (CAP) is an ionized gas with a near room temperature. CAP is a controllable source for reactive species, neutral particles, electromagnetic field and UV radiation. CAP showed the promising application in cancer treatment through the demonstration in vitro and in vivo. In this study, we first demonstrate the existence of an activation state on the CAP-treated cancer cells, which drastically decreases the threshold of cell vulnerability to the cytotoxicity of the CAP-originated reactive species such as H2O2 and NO2-. The cytotoxicity of CAP treatment is still dependent on the CAP-originated reactive species. The activation state of cancer cells will not cause noticeable cytotoxicity. This activation is an instantaneous process, started even just 2 s after the CAP treatment begins. The noticeable activation on the cancer cells starts 10-20 s during the CAP treatment. In contrast, the de-sensitization of activation takes 5 hours after the CAP treatment. The CAP-based cell activation explains the mechanism by which direct CAP treatment causes a much stronger cytotoxicity over the cancer cells compared with an indirect CAP treatment do, which is a key to understand what the effect of CAP on cancer cells.

Plasmas for Treating Cancer: Opportunities for Adaptive and Self-Adaptive Approaches.

Plasma is an ionized gas that is typically formed under high-temperature laboratory conditions. Recent progress in atmospheric plasmas has led to cold atmospheric plasma (CAP) devices with ion temperatures close to room temperature. The unique chemical and physical properties of CAP have led to its use in various biomedical applications including cancer therapy. CAP exhibits a spontaneous transition from a spatially homogeneous state to a modifiable pattern that is subject to self-organization. In this Opinion article, we discuss some new applications for plasma in cancer therapy based on plasma self-organization, which enables adaptive features in plasma-based therapeutic systems.

The Application of the Cold Atmospheric Plasma-Activated Solutions in Cancer Treatment.

BACKGROUND: Over the past five years, the cold atmospheric plasma-activated solutions (PAS) have shown their promissing application in cancer treatment. Similar as the common direct cold plasma treatment, PAS shows a selective anti-cancer capacity in vitro and in vivo. However, different from the direct cold atmospheric plasma (CAP) treatment, PAS can be stored for a long time and can be used without dependence on a CAP device. The research on PAS is gradually becoming a hot topic in plasma medicine. OBJECTIVES: In this review, we gave a concise but comprehensive summary on key topics about PAS including the development, current status, as well as the main conclusions about the anti-cancer mechanism achieved in past years. The approaches to make strong and stable PAS are also summarized.

The Strong Cell-based Hydrogen Peroxide Generation Triggered by Cold Atmospheric Plasma.

Hydrogen peroxide (H2O2) is an important signaling molecule in cancer cells. However, the significant secretion of H2O2 by cancer cells have been rarely observed. Cold atmospheric plasma (CAP) is a near room temperature ionized gas composed of neutral particles, charged particles, reactive species, and electrons. Here, we first demonstrated that breast cancer cells and pancreatic adenocarcinoma cells generated micromolar level H2O2 during just 1 min of direct CAP treatment on these cells. The cell-based H2O2 generation is affected by the medium volume, the cell confluence, as well as the discharge voltage. The application of cold atmospheric plasma (CAP) in cancer treatment has been intensively investigated over the past decade. Several cellular responses to CAP treatment have been observed including the consumption of the CAP-originated reactive species, the rise of intracellular reactive oxygen species, the damage on DNA and mitochondria, as well as the activation of apoptotic events. This is a new previously unknown cellular response to CAP, which provides a new prospective to understand the interaction between CAP and cells in vitro and in vivo. The short-lived reactive species in CAP may activate cells in vivo to generate long-lived reactive species such as H2O2, which may trigger immune attack on tumorous tissues via the H2O2-mediated lymphocyte activation.

The Specific Vulnerabilities of Cancer Cells to the Cold Atmospheric Plasma-Stimulated Solutions.

Cold atmospheric plasma (CAP), a novel promising anti-cancer modality, has shown its selective anti-cancer capacity on dozens of cancer cell lines in vitro and on subcutaneous xenograft tumors in mice. Over the past five years, the CAP-stimulated solutions (PSS) have also shown their selective anti-cancer effect over different cancers in vitro and in vivo. The solutions used to make PSS include several bio-adaptable solutions, mainly cell culture medium and simple buffered solutions. Both the CAP-stimulated medium (PSM) and the CAP-stimulated buffered solution (PSB) are able to significantly kill cancer cells in vitro. In this study, we systematically compared the anti-cancer effect of PSM and PSB over pancreatic adenocarcinoma cells and glioblastoma cells. We demonstrated that pancreatic cancer cells and glioblastoma cells were specifically vulnerable to PSM and PSB, respectively. The specific response such as the rise of intracellular reactive oxygen species of two cancer cell lines to the H2O2-containing environments might result in the specific vulnerabilities to PSM and PSB. In addition, we demonstrated a basic guideline that the toxicity of PSS on cancer cells could be significantly modulated through controlling the dilutability of solution.

Cold atmospheric plasma, a novel promising anti-cancer treatment modality.

Over the past decade, cold atmospheric plasma (CAP), a near room temperature ionized gas has shown its promising application in cancer therapy. Two CAP devices, namely dielectric barrier discharge and plasma jet, show significantly anti-cancer capacity over dozens of cancer cell lines in vitro and several subcutaneous xenograft tumors in vivo. In contrast to conventional anti-cancer approaches and drugs, CAP is a selective anti-cancer treatment modality. Thus far establishing the chemical and molecular mechanism of the anti-cancer capacity of CAP is far from complete. In this review, we provide a comprehensive introduction of the basics of CAP, state of the art research in this field, the primary challenges, and future directions to cancer biologists.

Enhancing cold atmospheric plasma treatment of cancer cells by static magnetic field.

It has been reported since late 1970 that magnetic field interacts strongly with biological systems. Cold atmospheric plasma (CAP) has also been widely studied over the past few decades in physics, biology, and medicine. In this study, we propose a novel idea to combine static magnetic field (SMF) with CAP as a tool for cancer therapy. Breast cancer cells and wild type fibroblasts were cultured in 96-well plates and treated by CAP with or without SMF. Breast cancer cells MDA-MB-231 showed a significant decrease in viability after direct plasma treatment with SMF (compared to only plasma treatment). In addition, cancer cells treated by the CAP-SMF-activated medium (indirect treatment) also showed viability decrease but was slightly weaker than the direct plasma-SMF treatment. By integrating the use of SMF and CAP, we were able to discover their advantages that have yet to be utilized. Bioelectromagnetics. 38:53-62, 2017. © 2016 Wiley Periodicals, Inc.