Polycationic γ‐Cyclodextrin with Amino Side Chains for a Highly Efficient Anti‐Heparin Coagulant

作者：W. Frank An, Zhuo Lei, Xiao‐Yong Yu, Chu‐Han Liu, Chen Zhang, Yong Chen, Yu Liu · 发表于：Advanced Healthcare Materials · 年份：2025 · DOI：10.1002/adhm.202404357 · 被引用次数：3 · 研究领域：Chemical Synthesis and Analysis、Heparin-Induced Thrombocytopenia and Thrombosis、Dendrimers and Hyperbranched Polymers

Abstract Multicharged cyclodextrins have attracted significant attention because of their applications in biology and pharmaceuticals. This study reports an aminoethoxy‐phenyl‐pyridinium‐modified γ‐cyclodextrin (PyA‐γ‐CD) as a highly efficient coagulant for heparin through multivalent interactions. The UV titration experiment is performed to obtain apparent binding constants (K obs ) between PyA‐γ‐CD and heparin as high as 9.85 × 10 6 M −1 . The activated partial thromboplastin time (aPTT) experiment in porcine plasma indicates that PyA‐γ‐CD 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‐γ‐CD for UFH, Dalte, Enoxa, and Nadro is 94%, 91%, 99%, and 85%, respectively. Interestingly, in vivo assays in mice further suggest that PyA‐γ‐CD significantly reverses the severe bleeding caused by heparin overdose while exhibiting remarkable biocompatibility. Therefore, PyA‐γ‐CD holds significant potential as a heparin antidote for clinical applications.