Synergistic cytotoxicity from cold atmospheric plasma and ultrasound in glioma cells

Abstract

The aim of this study was to investigate whether sonoporation of cancer cells using ultrasound (US) technology could enhance the anticancer effects of cold atmospheric plasma. US‐induced transient sonoporation of cancer cells with little to no cytotoxicity observed on the cell lines tested. Synergistic effects of US were observed when combined with both direct and indirect cold atmospheric plasma. These cytotoxic effects were dependent on reactive species production. To the best of our knowledge that is the first time that the effects of those two nonthermal technologies were evaluated in cancer cells, demonstrating a promising combined strategy for cancer therapies, particularly for those with penetration limitations, such as glioblastoma.

Ultrasound-mediated drug diffusion, uptake, and cytotoxicity in glioblastoma 3D tumour sphere model

“…We employed a 3D cell culture model to investigate the dispersion of cytotoxic reactive species and chemotherapeutics within the tumor sphere, assess the rate of cell death, and examine the impact of both single and multiple US treatments on cell-cell and cell-ECM interactions [26]. The effects of US on cancer cells have primarily been studied using 2D monolayer cell cultures [9, 20], and although an increasing number of studies are now utilizing animal models [21, 24]. We believe that this is the first time that the US 96 probe approach has been reported for drug diffusion through a tumour sphere, uptake by cells in a tumour sphere, and ultimately induced cytotoxicity in 3D tumour spheroids compared to 2D monolayer cells.…”

“…Our results demonstrate that US alone is capable of inducing cytotoxicity when cells/tumour spheres are exposed to prolonged durations of US, and that multiple treatments augment these effects. US-treated tumour spheres incubated for an extended duration (120 h) exhibited a notable reduction in cell viability and significantly more cell death compared with 8 h. When US exposure length and treatment frequency are increased, persistent pore formation in membranes, lysis, and ultimately cell death and tumour sphere damage result [9, 20]. The response to the US treatment exhibited a distinct kinetic pattern over time, differing significantly from the response observed with cold atmospheric plasma (CAP) treatment [26].…”

“…The effects of US on cancer cells have primarily been studied using 2D monolayer cell cultures [9,20], and although an increasing number of studies are now utilizing animal models [21,24].…”

“…Local fluid dynamics resulting from oscillating and/or collapsing cavitation bubbles are suggested to initiate the intracellular delivery mechanism induced by US [9, 19]. The plasma membrane of a cell may be torn apart by shearing or the direct contact of fluid with the cell, creating a transient pores [9, 20]. Through these pores, molecules may access the cytosol.…”