Review Article

ROS from Physical Plasmas: Redox Chemistry for Biomedical Therapy

Box 2

Current opportunities in the field of plasma medicine.
(1) New insights in redox chemistry and biology
Plasmas are ideal tools to generate gas phase-derived ROS on cells and tissues locally for certain species that would be otherwise difficult or impossible to generate at sufficient concentrations and with spatial limitation. For example, nitric oxide-rich plasmas can be used to study the effect of NO in several dermatological disorders in, e.g., animal models, potentially leading to new insights on redox chemical reactions in cells and tissues as well as their functional outcome.
(2) Multi-ROS tool to mimic multiple oxidative or nitrosative changes in inflammation
One of the hallmarks of inflammation is the generation of multiple ROS, including NO, HOCl, O2-, H2O2, and ONOO-, each having partially different effector functions. However, producing such species for inflammation research is not possible chemically. Cold physical plasmas overcome this challenge and may therefore be suitable tools to mimic the multi-ROS environment in inflammation research.
(3) Delivery of therapeutic ROS in redox-related diseases other than wound healing and cancer
In general, redox control is a critical event in the maintenance of tissue homeostasis. The relevance in wound healing and cancer as well actinic keratosis (with photodynamic therapy being one of the therapeutic options) is evident, and plasma has been successfully used for the treatment of these conditions in patients. However, diseases that also have so far not been considered to be treated with ROS therapy showed promising response after exposure to plasma. This includes fungal infections of the skin and the mucosal disease oral lichen planus. Increasing knowledge on the relevance of oxidative and nitrosative signalling events, e.g., nitration of tyrosine residues in protein kinases, further widens the potential scope of plasma.
(4) Precision medicine by disease-optimized ROS cocktails via specifically engineered plasmas
The type and amount of reactive species can be customized with plasma sources. Especially plasma jets are well suited for this task as their feed gas composition determines the reactive species output and hence the biological response. Optimized ROS compositions have been identified to eradicate for instance Staphylococcus aureus and THP-1 leukemia cells. With more in vivo evidence to come, the vision is to tailor plasma sources and ROS patterns specifically to promote the best efficacy for each pathological condition targeted by plasma treatment.