Gas Marble Therapeutics for the Mitigation of Cutaneous Injury Post-Radiation Exposure

PROJECT SUMMARY In the event of a radiological emergency, human skin tissues will suffer significant damage by ionization resulting in disrupted cellular repair processes and delayed wound healing. There has been a growing interest in utilizing gaseous molecules (H2, CO, NO, Xe) to treat cutaneous radiation injury as they exhibit promising abilities to regulate oxidative stress, reduce inflammation, provide cellular protection, and limit cellular senescence markers. However, delivery in the medical gas therapy domain has predominantly centered around inhalation-based methods requiring gas cylinders, which are impractical for radiological emergency scenarios. As a result, many gasotransmitters, noble gases, or traditional gases have not yet been tested for their ability to mitigate radiation- induced injuries. Recently, gas marble technology has emerged as a stable formulation by which to capture and contain gaseous species. The technology is made possible by the addition of partially wetted micro/nanoparticles to the air-liquid interface of liquid-entrapped gas. As this fortification strengthens resistance to mechanical stress and provides remarkable stability it is called a gas marble. These robust preparations could serve as an effective means of controlled delivery, encapsulating therapeutic gases to function as medical countermeasures against radiation exposure. The proposed study is for the investigation of medical gases (Xenon) as MCMs to mitigate and/or treat injury to normal skin cells arising from exposure to ionizing radiation in human tissue in vitro models. In parallel, computational modeling simulations will identify novel gas-protein targets. Additionally, the gas marble delivery system will be tested for the first time in a small animal model for its ability to deliver a known radiomitigating gas (H2) to ameliorate cutaneous radiation injury. Our Aims propose: (1) To investigate by computational and in vitro skin modeling, xenon gas's ability to bind to molecular targets and function as a specific drug that can mitigate ionizing radiation-induced biological responses; and (2) To demonstrate the in vivo feasibility of the gas marble technology for the skin delivery of established radiomitigating H2 gas against cutaneous radiation injury.