The Application of the Plasma Discharge Tube and Cold Plasma in Cancer Treatment
Open AccessCold Plasma Therapy has been shown to have a significant effect in the treatment of dozens of cancer types in both in vitro and in vivo models. Cold Plasma Therapy is based on the therapeutic effect of Cold Atmospheric Plasma (CAP). CAP is a kind of ionized gas close to room temperature, and it provides both electromagnetic radiation as well as Reactive Oxygen Species and Reactive Nitrogen Species (RONS), which are cytotoxic to cancer cells. 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. Here, we demonstrated the enhancement of therapeutic efficacy of TMZ via using a novel cold plasma source based on non-equilibrium plasma in a sealed glass tube, named radial cold Plasma Discharge Tube (PDT). PDT affected glioblastoma cells’ function by its electromagnetic (EM) emission rather than any chemical factors in plasma. 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. Furthermore, based on 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. PDT is not only independent of continuous Helium supply but also capable of resisting the interference of environmental changes. Thus, PDT was a stable and low-cost cold atmospheric plasma source. In short, this study first demonstrated the promising application of PDT in GBM therapy as a non-invasive and portable modality.A comparative study of the Tumor-Treating Fields treatment, cold atmospheric plasma treatment, and PDT treatment was performed. Tumor Treating Fields (TTFields) therapy has been well known and approved by the FDA for the treatment of adult patients suffering from glioblastoma. The method utilizes “low intensity” and “intermediate frequency” alternating electric fields to produce an inhibitory effect on cancerous cells. However, it involves a treatment time of 24 hours to show the anti-cancer effects. In this study, through the investigation of the anti-cancer effect of TTFields, CAP, and PDT on glioblastoma cells, we have found that CAP and PDT had a superior ability to inhibit cancer growth. Moreover, a 3D bioprinted skin tumor model with vascular channels was fabricated with gelatin methacryloyl (GelMA) bioink using a stereolithography-based bioprinting technique. Our 3D bioprinted skin tumor models can facilitate the integration of skin, skin tumor, and vascular channel structure to mimic the four stages of skin cancer development in the human body for studying the anti-cancer effect of CAPJ. The cell studies of the 3D bioprinted skin tumor model indicated that B16 and L929 cells proliferated well in the tissue model with time, suggesting this tissue model had good cytocompatibility to mimic the native skin cancer development. More importantly, the results demonstrated that CAPJ could drastically reduce the cell viability of cancer cells without damaging the normal cells in a 3D tissue microenvironment. It is expected that our bioprinted tumor model can be used for other cancer treatments, such as the plasma discharge tube, in future studies.
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