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We design two intestinal site\u2010specific microgels via Fe\n                    <jats:sup>3<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    \u2010COO\n                    <jats:sup>\u2212<\/jats:sup>\n                    coordination or STMP\u2010conjugated cross\u2010linking of eco\u2010friendly and biocompatible\n                    <jats:italic>Artemisia sphaerocephala<\/jats:italic>\n                    Krasch. polysaccharides (ASKP) extracted from desert sand\u2010fixing plant; these microgels release lactoferrin (Lf) precisely in the small intestine or colon on\u2010demand. Both microgels protect Lf from gastric digestion, preserve the Lf receptor (LfR)\u2010binding domain, and facilitate efficient LfR\u2010mediated endocytosis of Lf by intestinal epithelial cells. Small intestine\u2010targeted microgels regulate Lf metabolism, boost Lf bioavailability by \u22486\u2010fold, and drive marked hepatic Lf accumulation. These effects ameliorate alcoholic liver injury via the Nrf2\u2010mediated antioxidant pathway and CPT1A\u2010amplified fatty acid \u03b2\u2010oxidation after oral uptake. Colon\u2010targeted microgels alleviate ulcerative colitis by suppressing the TLR4\/MyD88\/NF\u2010\u03baB inflammatory axis and restoring gut microbiota homeostasis. Notably, this is the first demonstration of site\u2010specific intestinal delivery achieved by using different cross\u2010linking chemistries on the same ASKP backbone, enabling distinct gut\u2010regional specific therapeutic actions. This work establishes food\u2010grade microgel platforms as promising intestinal site\u2010specific delivery systems for spatiotemporally controlled, on\u2010demand delivery of bioactive proteins.\n                  <\/jats:p>","DOI":"10.1002\/advs.75697","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T15:01:57Z","timestamp":1778684517000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Microgel Platform Enables Site\u2010Specific Intestinal Delivery of Lactoferrin, Improving its Bioavailability for Targeted Alleviating Liver Injury and Colitis"],"prefix":"10.1002","volume":"13","author":[{"given":"Huiling","family":"Yan","sequence":"first","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality Department of Nutrition and Health China Agricultural University Beijing China"},{"name":"Research Center of Food Colloids and Delivery of Functionality 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