Navigating P-Selectin for Targeted Drug Delivery and Therapeutic Applications in Cancer and Inflammatory Disorders.

P-selectin, a cell adhesion molecule overexpressed in pathological conditions such as inflammation, thrombosis, and cancer, has emerged as a promising biomarker for targeted drug delivery. As a dynamic and disease-specific 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-selectin'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-selectin-targeting biomaterials, including polysaccharide derivatives, glycomimetics, antibodies, peptides, aptamers, and cell-mimetic carriers, which exploit P-selectin's affinity for its ligands. Advanced delivery systems leveraging these materials demonstrate enhanced efficacy in treating cancers, thrombotic disorders, atherosclerosis, ischemia-reperfusion injuries, rheumatoid arthritis, often synergized with exogenous stimuli (e.g., radiation) to spatiotemporally upregulate P-selectin expression. Challenges such as biodistribution optimization, scalability, and clinical translation are critically analyzed, alongside emerging strategies like dual-targeting and stimuli-responsive designs. By integrating multidisciplinary advances in nanotechnology, biomedical engineering, and biomimetics, P-selectin-based delivery systems offer a transformative approach to precision medicine, bridging mechanistic insights with therapeutic applications for inflammatory and oncological diseases.