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

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 (Fe(3)O(4)@AuNPs) as potential contrast agents. METHODS: Fe(3)O(4)@AuNPs were obtained by synthesizing iron oxide nanoparticles and gradually coating them with gold. The obtained Fe(3)O(4)@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 Fe(3)O(4)@AuNP-treated retinal pigment epithelium cells by WST-1 tests and in vivo by following histopathological changes in rats after injection of Fe(3)O(4)@AuNPs. RESULTS: Stable Fe(3)O(4)@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 Fe(3)O(4)@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 Fe(3)O(4)@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 T(2) signal in the MRI, which makes them suitable for candidates as contrast agent in small animal MRI applications.