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Gas plasma-oxidized sodium chloride acts via hydrogen peroxide in a model of peritoneal carcinomatosis
Lea Miebach1,2, Eric Freund1,2, Ramona Clemen1
1ZIK plasmatis, Leibniz Institute for Plasma Science and Technology, 17489 Greifswald, Germany.
Abstract:
Gas plasma technology generates reactive oxygen and nitrogen species (ROS/RNS), inducing lethal oxidative damage in tumor cells. The transfer of gas plasma-derived ROS/RNS into liquids has been proposed as an innovative anti-cancer strategy targeting peritoneal carcinomatosis (PC). However, the mechanism of action is under debate. To this end, we compared gas plasma-oxidized medical-grade sodium chloride (oxNaCl) with a concentration-matched control (cmc) of NaCl enriched with equivalent concentrations of H2O2 and NO3- in several cell lines and models of PC. Strikingly, oxNaCl and cmc performed equally well in oxidation and cytotoxic activity in tumor cells in two-dimensional cultures, three-dimensional (3D) tumor spheroids, vascularized 3D tumors grown on chicken-embryo chorioallantoic membranes, and a syngeneic PC mouse model in vivo. Given the importance of immunotherapies in oncology today, we focused on immunological consequences of the treatment. Again, to a similar extent, oxNaCl and cmc increased tumor cell immunogenicity and enhanced uptake by and maturation of peripheral blood monocyte-derived dendritic cells together with an inflammatory secretion profile. Furthermore, NanoString gene expression profiling revealed immune system processes and unfolded protein response-related pathways as being linked to the observed anti-tumor effects for both oxNaCl and cmc. In conclusion, gas plasma-generated oxNaCl and cmc showed equal therapeutic efficacy in our PC-related models. In light of the many promising anti-cancer studies of gas plasma-oxidized liquids and the convenient production of corresponding cmcs in large quantities as needed in clinics, our findings may spur research lines based on low-dose oxidants in peritoneal cancer therapy.
Insights
Gas plasma-oxidized sodium chloride and a control solution with similar oxidants show equal effectiveness against peritoneal carcinomatosis. This suggests low-dose oxidants may be a viable strategy for peritoneal cancer therapy.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Immunology
Background:
- Gas plasma technology generates reactive oxygen and nitrogen species (ROS/RNS) for anti-cancer effects.
- Transferring ROS/RNS into liquids is a proposed strategy for peritoneal carcinomatosis (PC).
- The precise mechanism of action for plasma-oxidized liquids in cancer treatment requires clarification.
Purpose of the Study:
- To compare the efficacy of gas plasma-oxidized medical-grade sodium chloride (oxNaCl) with a concentration-matched control (cmc) solution.
- To investigate the anti-tumor activity and immunological consequences of oxNaCl and cmc in various PC models.
- To elucidate the underlying molecular pathways involved in the anti-cancer effects.
Main Methods:
- Utilized cell lines, 3D tumor spheroids, and chicken-embryo models to assess cytotoxicity.
- Employed a syngeneic PC mouse model for in vivo evaluation.
- Analyzed immunological effects including dendritic cell maturation and cytokine profiles.
- Conducted NanoString gene expression profiling to identify molecular pathways.
Main Results:
- Both oxNaCl and cmc demonstrated comparable oxidation and cytotoxic activity against tumor cells in vitro and in vivo.
- Treatments similarly enhanced tumor cell immunogenicity and dendritic cell maturation.
- Both agents induced an inflammatory secretion profile.
- Gene expression analysis linked anti-tumor effects to immune system processes and unfolded protein response pathways.
Conclusions:
- Gas plasma-generated oxNaCl and concentration-matched control solutions exhibit equivalent therapeutic efficacy in peritoneal carcinomatosis models.
- The findings support the potential of low-dose oxidants for peritoneal cancer therapy.
- This research may encourage further investigation into plasma-oxidized liquids and oxidant-based strategies for cancer treatment.
