Assessment of Gold-Coated Iron Oxide Nanoparticles as Negative T2 Contrast Agent in Small Animal MRI Studies

Stefania D Iancu; Camelia Albu; Liviu Chiriac; Remus Moldovan; Andrei Stefancu; Vlad Moisoiu; Vasile Coman; Laszlo Szabo; Nicolae Leopold; Zoltán Bálint

doi:10.2147/IJN.S253184

Assessment of Gold-Coated Iron Oxide Nanoparticles as Negative T2 Contrast Agent in Small Animal MRI Studies

Int J Nanomedicine. 2020 Jul 7:15:4811-4824. doi: 10.2147/IJN.S253184. eCollection 2020.

Authors

Stefania D Iancu^{1

2}, Camelia Albu^{1

3}, Liviu Chiriac^{1

3

4}, Remus Moldovan^{1

3}, Andrei Stefancu^{1

2}, Vlad Moisoiu^{1

2

3}, Vasile Coman^{1

5}, Laszlo Szabo^{1

2}, Nicolae Leopold^{1

2}, Zoltán Bálint^{1

2}

Affiliations

¹ IMOGEN Medical Research Institute, County Clinical Emergency Hospital, Cluj-Napoca 400012, Romania.
² Faculty of Physics, Babeș-Bolyai University, Cluj-Napoca 400084, Romania.
³ Faculty of Medicine, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca 400349, Romania.
⁴ National Magnetic Resonance Center, Babeș-Bolyai University, Cluj-Napoca 400084, Romania.
⁵ Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, Cluj-Napoca 400372, Romania.

Abstract

Purpose: Magnetic resonance imaging (MRI) contrast agents are pharmaceuticals that enable a better visualization of internal body structures. In this study, we present the synthesis, MRI signal enhancement capabilities, in vitro as well as in vivo cytotoxicity results of gold-coated iron oxide nanoparticles (Fe₃O₄@AuNPs) as potential contrast agents.

Methods: Fe₃O₄@AuNPs were obtained by synthesizing iron oxide nanoparticles and gradually coating them with gold. The obtained Fe₃O₄@AuNPs were characterized by spectroscopies, transmission electron microscopy (TEM) and energy dispersive X-ray diffraction. The effect of the nanoparticles on the MRI signal was tested using a 7T Bruker PharmaScan system. Cytotoxicity tests were made in vitro on Fe₃O₄@AuNP-treated retinal pigment epithelium cells by WST-1 tests and in vivo by following histopathological changes in rats after injection of Fe₃O₄@AuNPs.

Results: Stable Fe₃O₄@AuNPs were successfully prepared following a simple and fast protocol (<1h worktime) and identified using TEM. The cytotoxicity tests on cells have shown biocompatibility of Fe₃O₄@AuNPs at small concentrations of Fe (<1.95×10^-8 mg/cell). Whereas, at higher Fe concentrations (eg 7.5×10^-8 mg/cell), cell viability decreased to 80.88±5.03%, showing a mild cytotoxic effect. MRI tests on rats showed an optimal Fe₃O₄@AuNPs concentration of 6mg/100g body weight to obtain high-quality images. The histopathological studies revealed significant transient inflammatory responses in the time range from 2 hours to 14 days after injection and focal cellular alterations in several organs, with the lung being the most affected organ. These results were confirmed by hyperspectral microscopic imaging of the same, but unstained tissues. In most organs, the inflammatory responses and sublethal cellular damage appeared to be transitory, except for the kidneys, where the glomerular damage indicated progression towards glomerular sclerosis.

Conclusion: The obtained stable, gold covered, iron oxide nanoparticles with reduced cytotoxicity, gave a negative T₂ signal in the MRI, which makes them suitable for candidates as contrast agent in small animal MRI applications.

Keywords: D407 cells; MRI contrast agent; cytotoxicity; gold-coated iron oxide nanoparticles; histopathology; rats.

MeSH terms

Animals
Cell Survival
Contrast Media / chemistry*
Endocytosis
Ferric Compounds / chemistry*
Gold / chemistry*
Inflammation / pathology
Magnetic Resonance Imaging*
Male
Metal Nanoparticles / chemistry*
Metal Nanoparticles / ultrastructure
Rats, Wistar
X-Ray Diffraction

Substances

Contrast Media
Ferric Compounds
ferric oxide
Gold

Grants and funding

Financial support from the Competitiveness Operational Programme 2014–2020 POC-A1-A1.1.4-E-2015, financed under the European Regional Development Fund, project number P37_245, is highly acknowledged.