First In Vitro Characterization of Salinomycinic Acid-Containing Two-Line Ferrihydrite Composites with Pronounced Antitumor Activity as MRI Contrast Agents

Author(s)
Irena Pashkunova-Martic, Joachim Friske, Daniela Paneva, Zara Cherkezova-Zheleva, Michaela Hejl, Michael Jakupec, Simone Braeuer, Peter Dorkov, Bernhard K Keppler, Thomas H Helbich, Juliana Ivanova
Abstract

Iron(III) (Fe(III)) complexes have recently emerged as safer alternatives to magnetic resonance imaging (MRI) contrast agents (CAs), reigniting interest in biomedical research. Although gadolinium Gd(III)-based contrast agents (CAs) have been widely used in MRI over the past four decades, their use in the current clinical routine is severely constrained due to concerns about high toxicity and environmental impact. Research is now focusing on synthesizing safer contrast agents with alternative paramagnetic ions like Fe(III) or Mn(II). MRI CAs with integrated potent therapeutic moieties may offer synergistic advantages over traditional contrast agents in clinical use. The study explored the use of salinomycin-ferrihydrite composites as possible effective ensembles of imaging and therapeutic units in the same molecule, evaluating their anticancer activity and influence on the signal in MRI. The composites were characterized using Mössbauer spectroscopy and ICP-MS for iron content determination. The in vitro relaxivity measurements in a high-field MR scanner demonstrated the potency of the composites as T

2 enhancers. The antitumor activity of one selected Sal-ferrihydrite composite was tested in three human cancer cell lines: A549 (non-small cell lung cancer); SW480 (colon cancer); and CH1/PA1 (ovarian teratocarcinoma) by the MTT cell viability assay. The new Sal-ferrihydrite composite showed a pronounced cytotoxicity in all three human cancers in line with enhanced signal in MRI, which makes it a promising candidate for future biomedical applications. The superior cytotoxic effect, together with the strong signal enhancement, makes these compounds promising candidates for further detailed investigations as future theranostic agents.

Organisation(s)
Department of Inorganic Chemistry
External organisation(s)
Medizinische Universität Wien, Bulgarian Academy of Sciences (BAS), University of Natural Resources and Life Sciences, Biovet Pvt Ltd, Sofia University "St. Kliment Ohridski"
Journal
International Journal of Molecular Sciences
Volume
26
ISSN
1422-0067
DOI
https://doi.org/10.3390/ijms26178405
Publication date
08-2025
Peer reviewed
Yes
Austrian Fields of Science 2012
104003 Inorganic chemistry, 302043 Magnetic resonance imaging (MRI), 104010 Macromolecular chemistry, 301207 Pharmaceutical chemistry
Keywords
ASJC Scopus subject areas
Molecular Biology, Spectroscopy, Catalysis, Inorganic Chemistry, Computer Science Applications, Physical and Theoretical Chemistry, Organic Chemistry
Sustainable Development Goals
SDG 3 - Good Health and Well-being
Portal url
https://ucrisportal.univie.ac.at/en/publications/63f14e34-ad99-433f-b7e2-3d0e173e32d9