Gas-Molecule-Mediated Radiosensitization in Cancer Therapy

Radiotherapy (RT) is one of the widely used cancer treatments, but its efficacy can be limited by the hypoxic tumor microenvironment (TME), which reduces reactive oxygen species (ROS) generation and promotes radioresistance. Recent studies suggest that gas small molecule-mediated sensitization may be a promising strategy for enhancing radiosensitivity. Therapeutic gas small molecules, including nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H₂S), ozone (O₃), hydrogen (H₂), and sulfur dioxide (SO₂), have demonstrated potential in regulating the TME. These gas small molecules have been shown to improve tumor oxygenation, promote ROS generation, induce DNA damage, and modulate immune responses, which may contribute to enhanced RT outcomes. This review summarizes the latest progress in gas small molecule-mediated radiosensitization strategies, focusing on the release mechanisms, therapeutic platforms, and potential clinical applications. Additionally, current challenges and future directions in this field are discussed, aiming to provide insights into optimizing the gas small molecule-mediated radiosensitization strategy.