Development of Polymer-Encapsulated, Amine-Functionalized Zinc Ferrite Nanoparticles as MRI Contrast Agents

Author:

Ilosvai Ágnes M.12,Forgách László3ORCID,Kovács Noémi34,Heydari Fatemeh3,Szigeti Krisztián3ORCID,Máthé Domokos34ORCID,Kristály Ferenc5ORCID,Daróczi Lajos6,Kaleta Zoltán78ORCID,Viskolcz Béla12ORCID,Nagy Miklós1ORCID,Vanyorek László1ORCID

Affiliation:

1. Institute of Chemistry, University of Miskolc, 3515 Miskolc, Hungary

2. Higher Education and Industrial Cooperation Centre, University of Miskolc, 3515 Miskolc, Hungary

3. Department of Biophysics and Radiation Biology, Semmelweis University, 1094 Budapest, Hungary

4. In Vivo Imaging Advanced Core Facility, Hungarian Center of Excellence for Molecular Medicine (HCEMM), 1094 Budapest, Hungary

5. Institute of Mineralogy and Geology, University of Miskolc, 3515 Miskolc, Hungary

6. Department of Solid State Physics, University of Debrecen, P.O. Box 2, 4010 Debrecen, Hungary

7. Pro-Research Laboratory, Progressio Engineering Bureau Ltd., 8000 Szekesfehervar, Hungary

8. Institute of Organic Chemistry, Semmelweis University, 1092 Budapest, Hungary

Abstract

The need for stable and well-defined magnetic nanoparticles is constantly increasing in biomedical applications; however, their preparation remains challenging. We used two different solvothermal methods (12 h reflux and a 4 min microwave, MW) to synthesize amine-functionalized zinc ferrite (ZnFe2O4-NH2) superparamagnetic nanoparticles. The morphological features of the two ferrite samples were the same, but the average particle size was slightly larger in the case of MW activation: 47 ± 14 nm (Refl.) vs. 63 ± 20 nm (MW). Phase identification measurements confirmed the exclusive presence of zinc ferrite with virtually the same magnetic properties. The Refl. samples had a zeta potential of −23.8 ± 4.4 mV, in contrast to the +7.6 ± 6.8 mV measured for the MW sample. To overcome stability problems in the colloidal phase, the ferrite nanoparticles were embedded in polyvinylpyrrolidone and could be easily redispersed in water. Two PVP-coated zinc ferrite samples were administered (1 mg/mL ZnFe2O4) in X BalbC mice and were compared as contrast agents in magnetic resonance imaging (MRI). After determining the r1/r2 ratio, the samples were compared to other commercially available contrast agents. Consistent with other SPION nanoparticles, our sample exhibits a concentrated presence in the hepatic region of the animals, with comparable biodistribution and pharmacokinetics suspected. Moreover, a small dose of 1.3 mg/body weight kg was found to be sufficient for effective imaging. It should also be noted that no toxic side effects were observed, making ZnFe2O4-NH2 advantageous for pharmaceutical formulations.

Funder

National Research, Development, and Innovation Fund

The European Union’s Horizon 2020 Research And Innovation Program

EU Programme

The cadre of the iMatrix consortium

Hungarian National Research, Development, and Innovation Office

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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