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Cold Plasma-Treated Ringer's Saline: A Weapon to Target Osteosarcoma
Miguel Mateu-Sanz1,2,3, Juan Tornín1,2,3, Bénédicte Brulin4
1Biomaterials, Biomechanics and Tissue Engineering Group, Department Materials Science and Metallurgy, Technical University of Catalonia (UPC), Escola d'Enginyeria Barcelona Est (EEBE), c/Eduard Maristany 14, 08019 Barcelona, Spain.
Abstract:
Osteosarcoma (OS) is the main primary bone cancer, presenting poor prognosis and difficult treatment. An innovative therapy may be found in cold plasmas, which show anti-cancer effects related to the generation of reactive oxygen and nitrogen species in liquids. In vitro models are based on the effects of plasma-treated culture media on cell cultures. However, effects of plasma-activated saline solutions with clinical application have not yet been explored in OS. The aim of this study is to obtain mechanistic insights on the action of plasma-activated Ringer's saline (PAR) for OS therapy in cell and organotypic cultures. To that aim, cold atmospheric plasma jets were used to obtain PAR, which produced cytotoxic effects in human OS cells (SaOS-2, MG-63, and U2-OS), related to the increasing concentration of reactive oxygen and nitrogen species generated. Proof of selectivity was found in the sustained viability of hBM-MSCs with the same treatments. Organotypic cultures of murine OS confirmed the time-dependent cytotoxicity observed in 2D. Histological analysis showed a decrease in proliferating cells (lower Ki-67 expression). It is shown that the selectivity of PAR is highly dependent on the concentrations of reactive species, being the differential intracellular reactive oxygen species increase and DNA damage between OS cells and hBM-MSCs key mediators for cell apoptosis.
Insights
Plasma-activated Ringer's saline (PAR) shows promise for treating osteosarcoma (OS) by selectively killing cancer cells. This innovative therapy utilizes reactive species generated by cold plasma, offering a potential new avenue for difficult-to-treat bone cancers.
Area of Science:
- Biomedical Engineering
- Oncology
- Plasma Physics
Background:
- Osteosarcoma (OS) is a primary bone cancer with poor prognosis and challenging treatments.
- Cold atmospheric plasma (CAP) exhibits anti-cancer properties via reactive oxygen and nitrogen species (RONS).
- Plasma-activated liquids, particularly saline solutions, have clinical potential but require further investigation for OS therapy.
Purpose of the Study:
- To investigate the therapeutic potential and mechanisms of plasma-activated Ringer's saline (PAR) against osteosarcoma.
- To explore the selective cytotoxic effects of PAR on OS cells versus healthy cells.
- To gain mechanistic insights into PAR's action in both cell cultures and organotypic models.
Main Methods:
- Cold atmospheric plasma jets were used to generate PAR from Ringer's saline.
- In vitro studies involved exposing human OS cell lines (SaOS-2, MG-63, U2-OS) and human bone marrow-derived mesenchymal stem cells (hBM-MSCs) to PAR.
- Organotypic cultures of murine OS were used to validate 2D findings, with histological analysis including Ki-67 staining.
Main Results:
- PAR demonstrated dose-dependent cytotoxic effects on human OS cells, correlating with increased RONS concentrations.
- PAR exhibited selectivity, with significant viability maintained in hBM-MSCs under the same treatment conditions.
- Organotypic cultures confirmed time-dependent cytotoxicity, and histological analysis revealed reduced proliferation (lower Ki-67 expression) in OS tissues.
- Differential increases in intracellular RONS and DNA damage between OS cells and hBM-MSCs were identified as key mediators of PAR-induced apoptosis.
Conclusions:
- PAR is a promising therapeutic agent for osteosarcoma, demonstrating selective cancer cell killing.
- The selectivity and efficacy of PAR are dependent on RONS concentration and the resulting differential cellular responses.
- PAR warrants further investigation for clinical applications in osteosarcoma treatment, leveraging its ability to induce apoptosis through ROS and DNA damage pathways.
