Molecular hydrogen in cancer therapy: Bioactive materials for tumor-targeted delivery and in situ generation

Molecular hydrogen (H₂) therapy has emerged as a promising adjunctive strategy in oncology, primarily attributed to its selective antioxidant, anti-inflammatory, and cytoprotective properties. Advances have been driven by the integration of mechanistic studies on H₂-mediated redox regulation, immunoregulation, and cytoprotective effects with rapid developments in nanotechnology and catalysis. Nevertheless, the clinical translation of H₂ therapy remains constrained by the present physicochemical limitations, including low solubility, non-targeted diffusion, the incomplete understanding of therapeutic mechanisms, etc. This review summarizes recent progress in molecular H₂ research, spanning from fundamental mechanisms in cancer biology, the role in adjuvant therapy, to the development of innovative catalytic delivery systems, such as stimuli-responsive materials and hydrogenases. We outline the pertinent challenges and future directions, emphasizing the need for mechanistic elucidation and robust clinical validation to integrate hydrogen therapy into precision oncology paradigms.