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As a dynamic and disease\u2010specific biomarker, its rapid translocation to cell surfaces upon injury or external stimuli, coupled with minimal expression in healthy tissues, enables precise therapeutic targeting. This review comprehensively examines P\u2010selectin's structural and functional roles in mediating leukocyte adhesion, platelet aggregation, and tumor metastasis, highlighting its potential as a dynamic target for drug delivery systems. We discuss diverse P\u2010selectin\u2010targeting biomaterials, including polysaccharide derivatives, glycomimetics, antibodies, peptides, aptamers, and cell\u2010mimetic carriers, which exploit P\u2010selectin's affinity for its ligands. Advanced delivery systems leveraging these materials demonstrate enhanced efficacy in treating cancers, thrombotic disorders, atherosclerosis, ischemia\u2013reperfusion injuries, rheumatoid arthritis, often synergized with exogenous stimuli (e.g., radiation) to spatiotemporally upregulate P\u2010selectin expression. Challenges such as biodistribution optimization, scalability, and clinical translation are critically analyzed, alongside emerging strategies like dual\u2010targeting and stimuli\u2010responsive designs. By integrating multidisciplinary advances in nanotechnology, biomedical engineering, and biomimetics, P\u2010selectin\u2010based delivery systems offer a transformative approach to precision medicine, bridging mechanistic insights with therapeutic applications for inflammatory and oncological diseases.<\/jats:p>","DOI":"10.1002\/adhm.70968","type":"journal-article","created":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T09:18:49Z","timestamp":1771665529000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Navigating P\u2010Selectin for Targeted Drug Delivery and Therapeutic Applications in Cancer and Inflammatory Disorders"],"prefix":"10.1002","volume":"15","author":[{"given":"Xiaonan","family":"Liu","sequence":"first","affiliation":[{"name":"School of Pharmacy Hangzhou Normal University  Hangzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Anti\u2010Cancer Chinese Medicines and Natural Medicines Hangzhou Normal University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Pharmacy Hangzhou Normal University  Hangzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Anti\u2010Cancer Chinese Medicines and Natural Medicines Hangzhou Normal University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Cai","sequence":"additional","affiliation":[{"name":"School of Pharmacy Hangzhou Normal University  Hangzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Anti\u2010Cancer Chinese Medicines and Natural Medicines Hangzhou Normal University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Hangzhou Normal University  Hangzhou China"},{"name":"Zhejiang Provincial Key Laboratory of 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