Advances in hydrogen delivery strategies for therapeutic applications

Molecular hydrogen (H₂) has emerged as a promising therapeutic agent owing to its selective antioxidant and anti-inflammatory properties, as well as its ability to modulate cellular signaling, metabolism, and immune responses. Beyond mitigating oxidative stress and inflammation, H₂ shows anticancer potential by altering the tumor microenvironment and inducing apoptosis. Despite encouraging findings from preclinical and clinical studies, conventional delivery routes-such as inhalation, oral intake of H₂-rich water, or injection of H₂-rich saline-face critical limitations in stability, bioavailability, and targeted delivery, impeding clinical translation. This review first outlines the therapeutic mechanisms of H₂, including redox regulation, inflammatory modulation, and tumor suppression. It then discusses current delivery approaches, their therapeutic outcomes, and inherent challenges. To overcome these barriers, a variety of advanced H₂-delivering systems have been developed, including H₂-containing carriers and in situ H₂-generating materials based on water-, acid-, and electrochemical reactions. Externally stimulated platforms, such as photo-, sono-, and electro-catalysis-based systems, enable spatiotemporally controlled H₂ release in response to disease-specific cues. Additionally, microbiota-targeted approaches involving probiotics and prebiotics offer indirect yet sustained H₂ delivery via gut fermentation. The review concludes by addressing key challenges-such as material scalability, biosafety, and integration with existing therapies-and highlights future directions for optimizing H₂ delivery through interdisciplinary innovation in materials science and medicine.