Marzena Wyskocka-Gajda, Łukasz Przypis, Monika Olesiejuk, Tomasz Krawczyk, Anna Kuźnik, Krzysztof Nawara, Masafumi Minoshima, Fuminori Sugihara, Kazuya Kikuchi, Nikodem Kuźnik
European journal of medicinal chemistry 2021 Feb 05The last 30 years of gadolinium-based "static" MRI contrast agents motivated to investigate bioresponsive agents with endogenous paramagnets. Iron(III) chelated by N,O-aminophenol skeleton of high versatility, and tuning potential was studied. The two-step convenient route of the ligand is characterized by high selectivity and allows for building a tunable chelate system. Functionalization with galactose endows a bioresponsive character sensitive to the enzyme activity. Direct relaxometric measurements of the resulting complexes revealed extremely high relaxivity of 5.62 mmol/dm3·s-1 comparable to classic gadolinium complexes. Enzymatic hydrolysis leads to relaxivity change by over 80%. Phantom MRI studies prove the bioresponsive character by contras percentage change within the range 40-275%. Cytotoxicity studies showed 70-90% viability of HeLa cells of the iron complexes. Proposed iron-based chelates with galactosidase-sensitive fragment express unequivocal relaxivity and MRI contras change and good biocompatibility. Therefore, these complexes are a promising step towards modern, bioresponsive MRI contrast agents with a "human-friendly" metal. Copyright © 2020 Elsevier Masson SAS. All rights reserved.
Marzena Wyskocka-Gajda, Łukasz Przypis, Monika Olesiejuk, Tomasz Krawczyk, Anna Kuźnik, Krzysztof Nawara, Masafumi Minoshima, Fuminori Sugihara, Kazuya Kikuchi, Nikodem Kuźnik. A step towards gadolinium-free bioresponsive MRI contrast agent. European journal of medicinal chemistry. 2021 Feb 05;211:113086
PMID: 33348236
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