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Herein, we reported that \u03b3\u2010glutamylcysteine (\u03b3GC) deletion in UC lesions intensified the disease by depleting intracellular GSH to induce macrophage ferroptosis, leading to macrophage M1 reprogramming and eventually exacerbating inflammation. To counteract this, the advanced microparticles (MPs)\u2010based delivery system is selected to encapsulate \u03b3GC. The resulting \u03b3GC\u2010MPs displayed the same porous and spiky morphology as their substrate's natural pollens, resulting in improved intestinal adhesion and enhanced lesion contact of \u03b3GC\u2010MPs. Our results demonstrated that exogenous \u03b3GC supplementation could inhibit macrophage M1 polarization by restraining ferroptosis, as well as suppressing the PI3K\/AKT pathway and TNF signaling pathway. Compared with free \u03b3GC, \u03b3GC\u2010MPs significantly alleviated typical UC symptoms in dextran sulfate sodium (DSS)\u2010induced colitis, evidenced by reduced intestinal inflammation, restored intestinal barrier function, and improved microbiota composition. Consequently, this study addressed critical gaps in understanding the causes of ferroptosis and its impact on macrophage reprogramming in UC, offering a novel synergistic therapeutic strategy for UC.<\/jats:p>","DOI":"10.1002\/advs.202503903","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T14:40:31Z","timestamp":1745937631000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Bioinspired Claw\u2010Engaged Adhesive Microparticles Armed with \u03b3GC Alleviate Ulcerative Colitis via Targeted Suppression of Macrophage Ferroptosis"],"prefix":"10.1002","volume":"12","author":[{"given":"Rong","family":"Wang","sequence":"first","affiliation":[{"name":"Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology College of Life Science Nanjing Normal University  Nanjing Jiangsu 210046 China"},{"name":"Hunan Provincial Key Laboratory of the Research and Development of Novel 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