PMID- 35357392 OWN - NLM STAT- MEDLINE DCOM- 20220506 LR - 20220706 IS - 2050-7518 (Electronic) IS - 2050-750X (Linking) VI - 10 IP - 17 DP - 2022 May 4 TI - Porous dynamic covalent polymers as promising reversal agents for heparin anticoagulants. PG - 3268-3276 LID - 10.1039/d2tb00174h [doi] AB - Heparins are natural and partially degraded polyelectrolytes that consist of sulfated polysaccharide backbones. However, as clinically used anticoagulants, heparins are associated with clinical bleeding risks and thus require rapid neutralization. Protamine sulfate is the only clinically approved antidote for unfractionated heparin (UFH), which not only may cause severe adverse reactions in patients, but also is only partially effective against low molecular weight heparins (LMWHs). We here present the facile synthesis of four porous multicationic dynamic covalent polymers (DCPs) from the condensation of tritopic aldehyde and acylhydrazine precursors. We show that, as new water-soluble polymeric antidotes, the new DCPs can effectively include both UFH and LMWHs and thus reverse their anticoagulating activity, which is confirmed by the activated partial thromboplastin time and thromboelastographic assays as well as mouse tail transection assay (bleeding model). The neutralization activities of two of the DCPs were found to be overall superior to that of protamine and have wider concentration windows and good biocompatibility. This pore-inclusion neutralization strategy paves the way for the development of water-soluble polymers as universal heparin binding agents. FAU - Zong, Yang AU - Zong Y AD - Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200438, China. zhouw@fudan.edu.cn. FAU - Xu, Yan-Yan AU - Xu YY AD - Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200438, China. zhouw@fudan.edu.cn. FAU - Wu, Yan AU - Wu Y AD - Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200438, China. zhouw@fudan.edu.cn. FAU - Liu, Yamin AU - Liu Y AUID- ORCID: 0000-0001-7344-1788 AD - Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200438, China. zhouw@fudan.edu.cn. FAU - Li, Qian AU - Li Q AD - Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200438, China. zhouw@fudan.edu.cn. FAU - Lin, Furong AU - Lin F AUID- ORCID: 0000-0001-5732-6253 AD - Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional Molecules, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China. frlin@sioc.ac.cn. FAU - Yu, Shang-Bo AU - Yu SB AUID- ORCID: 0000-0001-7186-367X AD - Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional Molecules, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China. frlin@sioc.ac.cn. FAU - Wang, Hui AU - Wang H AD - Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200438, China. zhouw@fudan.edu.cn. FAU - Zhou, Wei AU - Zhou W AUID- ORCID: 0000-0001-7467-3628 AD - Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200438, China. zhouw@fudan.edu.cn. FAU - Sun, Xing-Wen AU - Sun XW AUID- ORCID: 0000-0003-0432-7935 AD - Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200438, China. zhouw@fudan.edu.cn. FAU - Zhang, Dan-Wei AU - Zhang DW AUID- ORCID: 0000-0003-1244-1850 AD - Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200438, China. zhouw@fudan.edu.cn. FAU - Li, Zhan-Ting AU - Li ZT AUID- ORCID: 0000-0003-3954-0015 AD - Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200438, China. zhouw@fudan.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220504 PL - England TA - J Mater Chem B JT - Journal of materials chemistry. B JID - 101598493 RN - 0 (Anticoagulants) RN - 0 (Heparin, Low-Molecular-Weight) RN - 0 (Polymers) RN - 059QF0KO0R (Water) RN - 9005-49-6 (Heparin) SB - IM MH - Animals MH - *Anticoagulants/pharmacology/therapeutic use MH - Hemorrhage/chemically induced/drug therapy MH - *Heparin/chemistry/pharmacology MH - Heparin, Low-Molecular-Weight/pharmacology MH - Humans MH - Mice MH - Polymers/chemistry/pharmacology MH - Porosity MH - Water EDAT- 2022/04/01 06:00 MHDA- 2022/05/07 06:00 CRDT- 2022/03/31 12:05 PHST- 2022/04/01 06:00 [pubmed] PHST- 2022/05/07 06:00 [medline] PHST- 2022/03/31 12:05 [entrez] AID - 10.1039/d2tb00174h [doi] PST - epublish SO - J Mater Chem B. 2022 May 4;10(17):3268-3276. doi: 10.1039/d2tb00174h.