Gas-based therapeutics and delivery platforms in cancer immunotherapy

Abstract

Gas-based therapeutics are emerging as a promising strategy in cancer immunotherapy. Small gaseous signaling molecules such as nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H₂S), and oxygen (O₂) efficiently penetrate tumor tissues and modulate diverse immune pathways. These therapeutic gases can relieve tumor hypoxia, enhance immune cell infiltration, induce immunogenic cancer cell death, and suppress immunosuppressive signaling within the tumor microenvironment (TME). Therefore, they potentiate immune checkpoint blockade and other immunotherapies while overcoming key barriers to immune evasion. Despite this promise, the clinical translation of gas-based therapies faces significant challenges, including short half-lives, systemic toxicity, and lack of spatiotemporal control. To address these limitations, a variety of delivery platforms have been developed-from nanocarriers and injectable hydrogels to inhalable and oral prodrug formulations and stimuli-responsive systems-that enable safe, tumor-targeted, and controlled release of therapeutic gases. Such engineered strategies maximize antitumor efficacy while minimizing off-target effects. This review highlights the immunomodulatory roles of therapeutic gases, examines state-of-the-art delivery technologies, and discusses how these advances lay the foundation for precision gas immunotherapy to unlock the clinical potential of gaseous immunomodulators in cancer treatment.

Keywords: Cancer Immunotherapy; Gas Delivery Systems; Gasotransmitters; Stimuli-Responsive Nanocarriers.