Eda Gjika

Glioblastoma is one of the most aggressive brain cancers. Chemotherapy is a standard modality for its therapy. Here, we demonstrated a novel strategy using a helium gas discharge tube as a tunable electromagnetic emission source to sensitize glioblastoma cells to the cytotoxicity of temozolomide (TMZ), a widely used drug for glioblastoma. After a single 7-min of treatment, the efficacy of TMZ was enhanced in two typical glioblastoma cell lines U87MG and A172 without affecting a normal human astrocyte cell line hTERT/E6/E7. The discharge tube is a non-invasive approach, which provides a safe, controllable, stable, and low-cost modality to improve the conventional chemotherapy.

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.

Cold atmospheric plasma (CAP), an ionized gas operated at near-ambient temperatures, has been introduced as a new therapeutic opportunity for treating cancers. The effectiveness of the therapy has been linked to CAP-generated reactive oxygen and nitrogen species such as hydrogen peroxide and nitrite. In this study, we monitor in real-time cancer cell response to CAP over the course of 48 h. The results demonstrate a correlation between cell viability, exposure time (30, 60, 90, and 180 s), and discharge voltage (3.16 and 3.71 kV), while stressing the likely therapeutic role of plasma-generated reactive species. A 30–60 s increase in CAP exposure time and/or a discharge voltage adjustment from 3.16 to 3.71 kV is consistently accompanied by a significant reduction in cell viability. Comparably, levels of hydrogen peroxide and nitrite vary as a function of voltage with elevated levels detected at the highest tested voltage condition of 3.71 kV. CAP ultimately initiates a reduction in cell viability and triggers apoptosis via damage to the mitochondrial membrane, while also deregulating protein synthesis. The findings presented in this study are discussed in the context of facilitating the development of an adaptive CAP platform which could improve treatment outcomes.

Cold atmospheric plasma (CAP) treatment is a rapidly expanding and emerging technology for cancer treatment. Direct CAP jet irradiation is limited to the skin and it can also be invoked as a supplement therapy during surgery as it only causes cell death in the upper three to five cell layers. However, the current cannulas from which the plasma emanates are too large for intracranial applications. To enhance efficiency and expand the applicability of the CAP method for brain tumors and reduce the gas flow rate and size of the plasma jet, a novel micro-sized CAP device (µCAP) was developed and employed to target glioblastoma tumors in the murine brain. Various plasma diagnostic techniques were applied to evaluate the physics of helium µCAP such as electron density, discharge voltage, and optical emission spectroscopy (OES). The direct and indirect effects of µCAP on glioblastoma (U87MG-RedFluc) cancer cells were investigated in vitro. The results indicate that µCAP generates short- and long-lived species and radicals (i.e., hydroxyl radical (OH), hydrogen peroxide (H₂O₂), and nitrite (NO₂⁻), etc.) with increasing tumor cell death in a dose-dependent manner. Translation of these findings to an in vivo setting demonstrates that intracranial µCAP is effective at preventing glioblastoma tumor growth in the mouse brain. The µCAP device can be safely used in mice, resulting in suppression of tumor growth. These initial observations establish the µCAP device as a potentially useful ablative therapy tool in the treatment of glioblastoma.

Summary form only given. Cold atmospheric plasma (CAP) has received great attention due to their remarkable abilities in plasma medicine. Many scientists have successfully elucidated the potential of CAP as a novel technology against cancer1. CAP may be generated by a range of different plasma devices such as plasma jet, dielectric barrier discharge, corona discharge, gliding arc, etc2. However, most cancers occur inside the body and plasma direct irradiation is impractical as a clinical cancer therapy due to its high voltage, the formation of discharge in the organ, gas delivery, and plasma probe volume3,4. In addition, the heat inside the organ should be controllable and normal tissue should be protected from damage. In recent years, tiny, flexible, and easy to handle CAP devices have been considered for use in medical applications. In this context, here we developed a Micro-CAP (uCAP) device employing helium gas. The main objective was to investigate the effect of uCAP on glioblastoma cancer cells (U87) and glioblastoma tumors in the murine brain. Overall, our findings indicate that the newly developed uCAP can affect tumor growth . specifically, in-vitro results show that treatment of U87 glioblastoma cells with uCAP induces apoptosis. The rate of cell viablity under direct He uCAP application was much lower than indirect treatment, indicating that the cell apoptotic impact is by a synergistic effect of short and long-lived species (such as OH, H2O2, NO2-, et al) and radicals. In-vivo results demonstrate that the uCAP suppressed glioblastoma tumor growth, highlighting the translational potential of uCAP.

Cold Atmospheric Plasma (CAP) has received heightened attention as an alternative therapy due to its ability to impact cancer cells and trigger the activation of apoptosis [1, 2]. Shockingly, there has been limited investigation of the real time effects of CAP on cell viability immediately following treatment. When measuring and continuously monitoring the immediate effects of CAP on breast and gastric cancer cells using a cell viability assay, it was seen that plasma induced cell death. The data revealed a decrease in cell viability for 15 minutes after plasma treatment, followed by increased cell viability for up to 60 minutes. These results were attributed to the rapid proliferation rate of cancer cells. CAP treatment decreased cell viability in a dose dependent manner, with treatment durations between 30-180 seconds. Treatment with CAP for 180 seconds resulted in the slowest upward trend in viability up to a maximum of 70% at 60 minutes post treatment. The most significant and permanent effects of CAP were observed at 24 and 48 hours post treatment.