Gastrointestinal tract delivery of hydrogen by dynamic gas-releasing frameworks

Given the broad therapeutic benefits of molecular hydrogen, gastrointestinal delivery of this gasotransmitter is attractive for treating localized inflammatory diseases, yet conventional H2-releasing formulations suffer from limited solubility and poor tunability. Here, we develop gas-releasing frameworks (GRFs) for effective H2 delivery to the gastrointestinal tract. GRFs provide 20,000-fold higher hydrogen storage than hydrogen-rich water (HRW), prevent burst leakage in acidic gastric fluid, and enable sustained, inflammation-targeted H2 release in the intestine. After H2 release, the dynamic framework sequesters toxic boron within a reconstituted Si-O-B architecture, promoting fecal rather than systemic boron accumulation and improving long-term biosafety. Consequently, GRFs outperform HRW in mitigating oxidative damage and inflammation in dextran sulfate sodium-induced colitis, radiation-induced colitis, and high-fat diet-induced non-alcoholic fatty liver disease. Collectively, these gas-releasing frameworks provide a feasible, safe, and translatable strategy for gastrointestinal delivery of therapeutic gases and treatment of inflammatory disorders. Hydrogen therapy is limited by efficient storage and controlled release. Here, the authors show that gas-releasing frameworks enable high-capacity, sustained intestinal H2 delivery for management of multiple inflammatory disorders.