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Chelating polymers for hereditary hemochromatosis treatment
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SYSNO ASEP 0536333 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Chelating polymers for hereditary hemochromatosis treatment Author(s) Groborz, Ondřej (UMCH-V) ORCID, RID
Poláková, Lenka (UMCH-V) RID
Kolouchová, Kristýna (UMCH-V) ORCID, RID
Švec, Pavel (UMCH-V) RID, ORCID
Loukotová, Lenka (UMCH-V) RID, ORCID
Miriyala, Vijay Madhav (UOCHB-X) ORCID
Francová, P. (CZ)
Kučka, Jan (UMCH-V) RID, ORCID
Krijt, J. (CZ)
Páral, P. (CZ)
Báječný, M. (CZ)
Heizer, T. (CZ)
Pohl, Radek (UOCHB-X) RID, ORCID
Dunlop, David (UOCHB-X) ORCID
Czernek, Jiří (UMCH-V) RID
Šefc, L. (CZ)
Beneš, J. (CZ)
Štěpánek, Petr (UMCH-V) RID, ORCID
Hobza, Pavel (UOCHB-X) RID, ORCID
Hrubý, Martin (UMCH-V) RID, ORCIDArticle number 2000254 Source Title Macromolecular Bioscience. - : Wiley - ISSN 1616-5187
Roč. 20, č. 12 (2020), s. 1-16Number of pages 16 s. Language eng - English Country DE - Germany Keywords antioxidant ; experimental therapy ; hemochromatosis Subject RIV CD - Macromolecular Chemistry OECD category Polymer science Subject RIV - cooperation Institute of Organic Chemistry and Biochemistry - Inorganic Chemistry R&D Projects GA19-01438S GA ČR - Czech Science Foundation (CSF) GX19-27454X GA ČR - Czech Science Foundation (CSF) LO1507 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Research Infrastructure Czech-BioImaging II - 90129 - Ústav molekulární genetiky AV ČR, v. v. i.
CESNET II - 90042 - CESNET - zájmové sdružení právnických osob
CERIT-SC - 90085 - Masarykova univerzitaMethod of publishing Limited access Institutional support UMCH-V - RVO:61389013 ; UOCHB-X - RVO:61388963 UT WOS 000571110400001 EID SCOPUS 85091137091 DOI https://doi.org/10.1002/mabi.202000254 Annotation Hemochromatosis (iron overload) encompasses a group of diseases that are characterized by a toxic hyperaccumulation of iron in parenchymal organs. Currently, only few treatments for this disease have been approved. However, all these treatments possess severe side effects. In this study, a paradigm for hemochromatosis maintenance/preventive therapy is investigated: polymers with negligible systemic biological availability form stable complexes with iron ions in the gastrointestinal tract, which reduces the biological availability of iron. Macroporous polymer beads are synthesized with three different iron‐chelating moieties (benzene‐1,2‐diol, benzene‐1,2,3‐triol, and 1,10‐phenanthroline). The polymers rapidly chelate iron ions from aqueous solutions in vitro in the course of minutes, and are noncytotoxic and nonprooxidant. Moreover, the in vivo biodistribution and pharmacokinetics show a negligible uptake from the gastrointestinal tract (using 125I‐labeled polymer and single photon emission computed tomography/computed tomography), which generally prevents them from having systemic side effects. The therapeutic efficacy of the prepared polymers is successfully tested in vivo, and exhibits a significant inhibition of iron uptake from the gastrointestinal tract without any noticeable signs of toxicity. Furthermore, an in silico method is developed for the prediction of chelator selectivity. Therefore, this paradigm can be applied to the next‐generation maintenance/preventive treatment for hemochromatosis and/or other diseases of similar pathophysiology. Workplace Institute of Macromolecular Chemistry Contact Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Year of Publishing 2021 Electronic address https://onlinelibrary.wiley.com/doi/10.1002/mabi.202000254
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