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Today, oral anticoagulants are considered equivalent alternatives to low molecular weight heparin (LMWH) in guideline\u2010based treatments of cancer\u2010associated thromboses. Nevertheless, debates on potential antitumorigenic heparin activities beyond anticoagulation are still highly relevant. However, disclosure of heparin targeted activities is complicated by the heterogeneous structure of this glycosaminoglycan of natural origin. Therefore, synthetic polymers appear promising as heparin mimetics to interfere with different steps in tumor metastatic spread. Here, the synthesis of noncarbohydrate copolymers of itaconic acid is described with either potassium\u20103\u2010sulfopropylmethacrylate (SPMA), sodium 4\u2010styrenesulfonate (SS), or 2\u2010acrylamido\u20102\u2010methyl\u20101\u2010propanesulfonate (AMPS) via reversible addition\u2010fragmentation\u2010chain\u2010transfer (RAFT) polymerization. The copolymers, characterized by GPC, display high efficiencies to inhibit heparanase enzymatic activity, exceeding the potency of the clinical candidate PG545. The SS\u2010copolymers (poly(SS\u2010\n                    <jats:italic>co<\/jats:italic>\n                    \u2010IA)) outperform the other copolymers and LMWH in blocking tumor cell\u2010induced platelet activation (TCIPA), thus platelet degranulation or aggregation as key issues in metastasis by reducing thrombin formation. The cytotoxicity of poly(SS\u2010\n                    <jats:italic>co<\/jats:italic>\n                    \u2010IA) is very low. Notably, poly(SS\u2010\n                    <jats:italic>co<\/jats:italic>\n                    \u2010IA) copolymers displayed a thousand\u2010fold lower binding affinity to platelet factor\u20104 (PF4) than unfractionated heparin (UFH), suggesting a lower risk for HIT II susceptibility. The indicated polymers represent promising heparin mimetics with superior activities in oncology for metastatic control.\n                  <\/jats:p>","DOI":"10.1002\/mabi.202400633","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T15:22:02Z","timestamp":1744039322000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Novel Series of Synthetic Heparin\u2010Mimetics\u2013Itaconic Acid\u2010Containing Copolymers for Targeting Tumor Cell Coagulability and Metastasis"],"prefix":"10.1002","volume":"25","author":[{"given":"Katrin","family":"Nekipelov","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Bonn  An der Immenburg 4 53121 Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah Al","family":"Nahain","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Bioscience University of Queensland  Brisbane Queensland 4072 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Otto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Bonn  An der Immenburg 4 53121 Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongbin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology The Biomedical Center University of Uppsala  Uppsala 75123 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology The Biomedical Center University of Uppsala  Uppsala 75123 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Letunica","sequence":"additional","affiliation":[{"name":"Haematology Research Murdoch Children's Research Institute The Department of Paediatrics University of Melbourne Department of Clinical Haematology Royal Children's Hospital  Parkville Victoria 3052 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Collett","sequence":"additional","affiliation":[{"name":"Haematology Research Murdoch Children's Research Institute The Department of Paediatrics University of Melbourne Department of Clinical Haematology Royal Children's Hospital  Parkville Victoria 3052 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Attard","sequence":"additional","affiliation":[{"name":"Haematology Research Murdoch Children's Research Institute The Department of Paediatrics University of Melbourne Department of Clinical Haematology Royal Children's Hospital  Parkville Victoria 3052 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Monagle","sequence":"additional","affiliation":[{"name":"Haematology Research Murdoch Children's Research Institute The Department of Paediatrics University of Melbourne Department of Clinical Haematology Royal Children's Hospital  Parkville Victoria 3052 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Vamvounis","sequence":"additional","affiliation":[{"name":"College of Science and Engineering James Cook University  Townsville Queensland 4811 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Tsanaktsidis","sequence":"additional","affiliation":[{"name":"CSIRO Manufacturing Research Way  Clayton Victoria 3168 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito","family":"Ferro","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Bioscience University of Queensland  Brisbane Queensland 4072 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8667-7201","authenticated-orcid":false,"given":"Gerd","family":"Bendas","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Bonn  An der Immenburg 4 53121 Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,7]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.3949\/ccjm.91a.23017"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-053736"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.12.014"},{"key":"e_1_2_9_3_2","unstructured":"b)Treatment of cancer\u2010associated venous thromboembolismhttps:\/\/www.escardio.org\/Councils\/Council\u2010for\u2010Cardiology\u2010Practice\u2010(CCP)\/Cardiopractice\/treatment\u2010of\u2010cancer\u2010associated\u2010venous\u2010thromboembolism; 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