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Chelating polymers for hereditary hemochromatosis treatment

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    SYSNO ASEP0536333
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleChelating 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)
    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, ORCID
    Article number2000254
    Source TitleMacromolecular Bioscience. - : WILEY-BLACKWELL - ISSN 1616-5187
    Roč. 20, č. 12 (2020), s. 1-16
    Number of pages16 s.
    Languageeng - English
    CountryDE - Germany
    Keywordsantioxidant ; experimental therapy ; hemochromatosis
    Subject RIVCD - Macromolecular Chemistry
    OECD categoryPolymer science
    Subject RIV - cooperationInstitute of Organic Chemistry and Biochemistry - Inorganic Chemistry
    R&D ProjectsGA19-01438S GA ČR - Czech Science Foundation (CSF)
    GX19-27454X GA ČR - Czech Science Foundation (CSF)
    LO1507 GA MŠk - Ministry of Education, Youth and Sports (MEYS)
    Research InfrastructureCzech-BioImaging II - 90129 - Ústav molekulární genetiky AV ČR, v. v. i.
    CESNET II - 90042 - CESNET - zájmové sdružení právnických osob
    CERIT-SC - 90085 - Masarykova univerzita
    Method of publishingLimited access
    Institutional supportUMCH-V - RVO:61389013 ; UOCHB-X - RVO:61388963
    UT WOS000571110400001
    EID SCOPUS85091137091
    DOI10.1002/mabi.202000254
    AnnotationHemochromatosis (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.
    WorkplaceInstitute of Macromolecular Chemistry
    ContactEva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358
    Year of Publishing2021
    Electronic addresshttps://onlinelibrary.wiley.com/doi/10.1002/mabi.202000254
Number of the records: 1