A Promising Biomimetic Hydrogen Sulfide System for Advancing Inflammatory Disease Treatment.

Hydrogen sulfide (H2S) exhibits a Janus-faced nature in the regulation of inflammatory diseases, acting as both a therapeutic agent and a pathological aggravator. Effectively harnessing its beneficial effects while mitigating its harmful impacts is pivotal for advancing H2S-based therapies. Here, an innovative H2S supply system is introduced that enables H2S to primarily exhibit its therapeutic effects. Unlike conventional synthetic H2S donor-based strategies, a biomimetic H2S supply system (termed CP) is presented that mimics endogenous enzymatic H2S production. The CP sustainably produces H2S at a constant rate throughout the dosing period, ensuring therapeutic benefits while avoiding toxicity. Furthermore, by functionalizing CP with hyaluronic acid, the resulting system (CPH) not only achieves targeted delivery to inflammatory bowel disease (IBD) tissues but also provides controllable H2S production within the diseased microenvironment. Consequently, CPH significantly mitigates immune inflammation, promotes intestinal epithelial barrier repair, and modulates gut microbiota by sustainably and constantly supplying the multifunctional H2S. This study revolutionizes the H2S supply strategies and provides new insights into gas-based therapies.