Abstract
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.
Highlights
Plasma is an ionized gas consisting of positive/negative charges, radicals, neural atoms and ultraviolet (UV) photons, that is, a gaseous matter with quasi-neutral charges [1,2,3]
The efficacy of Cold atmospheric plasma (CAP) in the proposed applications relies on the synergistic action of the reactive oxygen species (ROS), reactive nitrogen species (RNS), free radicals, UV photons, charged particles, and electric fields [12,13,14,15]
Our findings suggest that both He μCAP direct/indirect treatment could induce high cell death in glioblastoma cancer cells (Figure 6), in general direct treatment was more effective than indirect treatment
Summary
Plasma is an ionized gas consisting of positive/negative charges, radicals, neural atoms and ultraviolet (UV) photons, that is, a gaseous matter with quasi-neutral charges [1,2,3]. Atmospheric plasma at or near ambient temperature has led to a new field of plasma medicine [4,5], and cold atmospheric plasma (CAP) has attracted a lot of attentions due to its remarkable potential to affect biological processes [2,6]. In this context, the potential of CAP in diverse bio-medical applications has been explored, including disinfection, wound treatments, control of inflammation, blood coagulation, Cancers 2017, 9, 61; doi:10.3390/cancers9060061 www.mdpi.com/journal/cancers. Some results indicated that exposing cancer cells to CAP resulted in the production of free radicals that could cause apoptotic cell death [20]
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