Synthesis, characterization, in vitro phantom imaging, and cytotoxicity of a novel graphene-based multimodal magnetic resonance imaging-X-ray computed tomography contrast agent

Graphene nanoplatelets (GNPs), synthesized by potassium permanganate-based oxidation and exfoliation followed by reduction with hydroiodic acid (rGNP-HI), intercalated with manganese ions within the graphene sheets, and covalently functionalized with iodine, exhibit excellent potential as biomodal contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT). Structural characterization of rGNP-HI nanoparticles with low- and high-resolution transmission electron microscopy (TEM) showed disc-shaped nanoparticles (average diameter, 200 nm and average thickness, 3 nm). Energy dispersive X-ray spectroscopy (EDX) analysis confirmed the presence of intercalated manganese. Raman spectroscopy and X-ray diffraction (XRD) analysis of rGNP-HI confirmed the reduction of oxidized GNPs (O-GNPs), the absence of molecular and physically-adsorbed iodine, and the functionalization of graphene with iodine as polyiodide complexes (I-3(-) and I-5(-)). Manganese and iodine contents were quantified to be 5.1 +/- 0.5 and 10.54 +/- 0.87 wt% by inductively coupled plasma optical emission spectroscopy and ion-selective electrode measurements, respectively. In vitro cytotoxicity analysis, using absorbance (LDH assay) and fluorescence (calcein AM) assays, performed on NIH3T3 mouse fibroblasts and A498 human kidney epithelial cells, indicated CD50 values of rGNP-HI between 179 and 301 mu g ml(-1), depending on the cell line and the cytotoxicity assay. CT and MRI phantom imaging of rGNP-HI displayed high CT (approximately 3200% greater than that of HI at equimolar iodine concentration) and MRI (approximately 59% greater than that of an equimolar Mn2+ solution) contrast. These results open avenues for further in vivo safety and efficacy studies towards the development of carbon nanostructure-based multimodal MRI-CT contrast agents.