Murphy William, Horkowitz Alex, Soni Vikas, Walkiewicz-Yvon Camil, Keidar Michael
Micropropulsion and Nanotechnology Laboratory (MPNL), School of Engineering and Applied Science, George Washington University, 800 22nd St. NW, Suite 3100, Washington, DC 20052, USA.
Cancers (Basel). 2025 Jun 18;17(12):2036. doi: 10.3390/cancers17122036.
Glioblastoma (GBM) resists current therapies due to its rapid proliferation, diffuse invasion, and heterogeneous cell populations. We previously showed that a single cold atmospheric plasma discharge tube (DT) reduces GBM viability via broad-spectrum electromagnetic (EM) emissions. Here, we tested whether two DTs arranged in a helmet configuration could generate overlapping EM fields to amplify the anti-tumor effects without thermal injury.
The physical outputs of the single- and dual-DT setups were characterized by infrared thermography, broadband EM field probes, and oscilloscope analysis. Human U87-MG cells were exposed under the single or dual configurations. The viability was quantified with WST-8 assays mapped across 96-well plates; the intracellular reactive oxygen species (ROS), membrane integrity, apoptosis, and mitochondrial potential were assessed by multiparametric flow cytometry. Our additivity models compared the predicted versus observed dual-DT cytotoxicity.
The dual-DT operation produced constructive EM interference, elevating electric and magnetic field amplitudes over a broader area than either tube alone, while temperatures remained <39 °C. The single-DT exposure lowered the cell viability by ~40%; the dual-DT treatment reduced the viability by ~60%, exceeding the additive predictions. The regions of greatest cytotoxicity co-localized with the zones of highest EM field overlap. The dual-DT exposure doubled the intracellular ROS compared with single-DT and Annexin V positivity, confirming oxidative stress-driven cell death. The out-of-phase operation of the discharge tubes enabled the localized control of the treatment regions, which can guide future treatment planning.
Two synchronously operated plasma discharge tubes synergistically enhanced GBM cell killing through non-thermal mechanisms that coupled intensified overlapping EM fields with elevated oxidative stress. This positions modular multi-DT arrays as a potential non-invasive adjunct or alternative to existing electric-field-based therapies for glioblastoma.
胶质母细胞瘤(GBM)因其快速增殖、弥漫性侵袭和异质性细胞群体而对当前治疗产生抵抗。我们之前表明,单个冷大气等离子体放电管(DT)通过广谱电磁(EM)发射降低GBM的活力。在此,我们测试了以头盔配置排列的两个DT是否能产生重叠的EM场,以增强抗肿瘤效果而不造成热损伤。
通过红外热成像、宽带EM场探头和示波器分析对单DT和双DT设置的物理输出进行表征。将人U87-MG细胞暴露于单配置或双配置下。用WST-8测定法对96孔板上的细胞活力进行定量;通过多参数流式细胞术评估细胞内活性氧(ROS)、膜完整性、凋亡和线粒体电位。我们的相加模型比较了预测的和观察到的双DT细胞毒性。
双DT操作产生相长性EM干扰,与单独的任何一个管子相比,在更广泛的区域提高了电场和磁场幅度,而温度保持在<39°C。单DT暴露使细胞活力降低约40%;双DT处理使活力降低约60%,超过相加预测值。最大细胞毒性区域与最高EM场重叠区域共定位。与单DT相比,双DT暴露使细胞内ROS增加一倍,膜联蛋白V阳性率增加,证实了氧化应激驱动的细胞死亡。放电管的异相操作实现了治疗区域的局部控制,这可为未来的治疗规划提供指导。
两个同步操作的等离子体放电管通过非热机制协同增强了GBM细胞杀伤,该机制将增强的重叠EM场与升高的氧化应激相结合。这使模块化多DT阵列成为胶质母细胞瘤现有基于电场疗法的潜在非侵入性辅助或替代方法。