Metabolomics Study on In Vivo Biosafety Assessment of Gadolinium-based Nanoparticulate Contrast Agents Modified by Polyethylene Glycol

To enhance the effect of magnetic resonance imaging (MRI), nanoparticulate contrast agents have become a new research field in recent years. Due to the unique physical and chemical properties of nanomaterials and the complexity of biological systems, the biological safety of nanoparticulate contrast agents should be further studied. In this work, polyethylene glycol-modified gadolinium sodium tetrafluoride (PEG-NaGdF4) nanoparticulate contrast agent was firstly constructed. Then, the MRI effect of PEG-NaGdF4 was investigated. To evaluate the biosafety of as-prepared PEG-NaGdF4, the mechanism of action of different concentrations of PEG- NaGdF4 in rats at metabolic level was studied by ultra high performance liquid chromatography-electrospray- quadrupole time of flight-mass spectrometry (UPLC-ESI-QTOF/MS). The results showed that the high dose of PEG- NaGdF4 (100 mu g/mL) could induce abnormality of tryptophan metabolism, arginine and proline metabolism, phenylalanine metabolism, tricarboxylic acid cycle, purine metabolism, bile acid metabolism and fatty acid metabolism in rats for a short period of time, and also cause inflammation and kidney damage to a certain extent. Moderate dose (50 mu g/mL) and low dose (25 mu g/mL) of PEG-NaGdF4 had little effect on metabolism in rats. In combination with the results of MRI and metabolomics, the moderate dose of PEG-NaGdF4 (50 mu g/mL) showed good MRI performance and biocompatibility, which might hold great promise in biomedical applications.