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

Abstract

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– 3 Vasile Coman,1,5 Laszlo Szabo,1,2 Nicolae Leopold,1,2 Zoltán Bálint1,2 1IMOGEN Medical Research Institute, County Clinical Emergency Hospital, Cluj-Napoca 400012, Romania; 2Faculty of Physics, Babeș-Bolyai University, Cluj-Napoca 400084, Romania; 3Faculty of Medicine, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca 400349, Romania; 4National Magnetic Resonance Center, Babeș-Bolyai University, Cluj-Napoca 400084, Romania; 5Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, Cluj-Napoca 400372, RomaniaCorrespondence: Zoltán Bálint Email [email protected]: 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 [email protected]: 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: MRI contrast agent, gold-coated iron oxide nanoparticles, cytotoxicity, D407 cells, histopathology, rats

Keywords

• mri contrast agent
• gold-coated iron oxide nanoparticles
• cytotoxicity
• histopathology
• animal model
• hyperspectral imaging.