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This study reports an aminoethoxy\u2010phenyl\u2010pyridinium\u2010modified \u03b3\u2010cyclodextrin (PyA\u2010\u03b3\u2010CD) as a highly efficient coagulant for heparin through multivalent interactions. The UV titration experiment is performed to obtain apparent binding constants (K<jats:sub>obs<\/jats:sub>) between PyA\u2010\u03b3\u2010CD and heparin as high as 9.85 \u00d7 10<jats:sup>6<\/jats:sup>\u00a0M<jats:sup>\u22121<\/jats:sup>. The activated partial thromboplastin time (aPTT) experiment in porcine plasma indicates that PyA\u2010\u03b3\u2010CD not only exhibits nearly complete neutralization activity for unfractionated heparin (UFH), but more importantly, it also effectively neutralizes three LMWHs (dalteparin (Dalte), enoxaparin (Enoxa), and nadroparin (Nadro)) with a broader therapeutic window compared to protamine. The top neutralization activity of PyA\u2010\u03b3\u2010CD for UFH, Dalte, Enoxa, and Nadro is 94%, 91%, 99%, and 85%, respectively. Interestingly, in vivo assays in mice further suggest that PyA\u2010\u03b3\u2010CD significantly reverses the severe bleeding caused by heparin overdose while exhibiting remarkable biocompatibility. Therefore, PyA\u2010\u03b3\u2010CD holds significant potential as a heparin antidote for clinical applications.<\/jats:p>","DOI":"10.1002\/adhm.202404357","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T01:55:52Z","timestamp":1736128552000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Polycationic \u03b3\u2010Cyclodextrin with Amino Side Chains for a Highly Efficient Anti\u2010Heparin Coagulant"],"prefix":"10.1002","volume":"14","author":[{"given":"Wen\u2010Jin","family":"An","sequence":"first","affiliation":[{"name":"College of Chemistry State Key Laboratory of Elemento\u2010Organic Chemistry Nankai University  Tianjin 300071 P. R. 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