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

Abstract

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.