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Although the endogenous gasotransmitter hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) possesses potent anti\u2010inflammatory and antioxidant properties, its therapeutic application is hindered by rapid clearance, uncontrolled release profiles, and a narrow therapeutic window. Here, we present a macrophage\u2010targeted and pH\u2010responsive H\n                    <jats:sub>2<\/jats:sub>\n                    S delivery nanoplatform constructed by encapsulating acid\u2010labile zinc sulfide within a zeolitic imidazolate framework\u20108 (ZIF\u20108) and functionalizing the nanoparticle surface with folate ligands (ZIF\u2010H\n                    <jats:sub>2<\/jats:sub>\n                    S\u2010FA). This strategy exploits the overexpression of folate receptors on pro\u2010inflammatory M1 macrophages to ensure preferential cellular uptake. Following endocytosis, lysosomal acidity triggers framework degradation, sustaining the intracellular release of Zn\n                    <jats:sup>2+<\/jats:sup>\n                    and H\n                    <jats:sub>2<\/jats:sub>\n                    S. These components synergistically scavenge reactive oxygen species (ROS) and suppress NF\u2010\u03baB signaling, effectively reprogramming macrophages from an inflammatory toward a regenerative M2 phenotype. In a rat OA model, intra\u2010articular administration of ZIF\u2010H\n                    <jats:sub>2<\/jats:sub>\n                    S\u2010FA demonstrates prolonged joint retention, effective scavenging of oxidative stress, alleviation of cartilage destruction, and reduced osteoclast activity, without systemic toxicity. This study establishes a targeted H\n                    <jats:sub>2<\/jats:sub>\n                    S delivery strategy that enables precise immunomodulation, providing a feasible therapeutic approach for OA and other inflammation\u2010associated disorders.\n                  <\/jats:p>","DOI":"10.1002\/smll.76131","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:19:13Z","timestamp":1791476353000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted Intracellular Hydrogen Sulfide Delivery to Inflammatory Macrophages Reprograms Polarization and Mitigates Oxidative Stress in Osteoarthritis"],"prefix":"10.1002","author":[{"given":"Zhen","family":"Zhang","sequence":"first","affiliation":[{"name":"Orthopedics Department Shenzhen Children's Hospital Affiliated to Shantou University Medical College  Shenzhen Guangdong China"},{"name":"Center for AI\u2010Driven Medical 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