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Chelating polymers for hereditary hemochromatosis treatment

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) 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 number	2000254
Source Title	Macromolecular Bioscience. - : Wiley - ISSN 1616-5187 Roč. 20, č. 12 (2020), s. 1-16
Number 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 univerzita
Method of publishing	Limited access
Institutional support	UMCH-V - RVO:61389013 ; UOCHB-X - RVO:61388963
UT WOS	000571110400001
EID SCOPUS	85091137091
DOI	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

Number of the records: 1