Metabolomics Study On In Vivo Safety Assessment Of Gadolinium-based Nanoparticle Contrast Agents Modified By Polyethylene Glycol

Magnetic resonance imaging（MRI）is widely used in disease diagnosis.Magnetic resonance imaging contrast agents have been developed for clinical procedures in order to obtain richer and more detailed tissue imaging information.In recent years,to improve the MRI quality,nanoparticles applied as contrast agents have been intensively studied.However,the biosafety of nano-scale contrast agents is a primary issue in clinical translational research,and their biosafety evaluations have attracted much scientific attention.In this study,the PEG-Na Gd F₄ nano-scale contrast agent was constructed and a urinary metabolomics analysis based on UPLC-ESI-QTOF-MS was employed to evaluate the metabolic response of PEG-Na Gd F₄ nano-scale contrast in rats.（1）PEG-Na Gd F₄ nanoparticles were synthesized by hydrothermal synthesis,and the physicochemical properties were systematically studied by various characterization methods.What’s more,in vitro and in vivo magnetic resonance imagings were performed on PEG-Na Gd F₄ nanoparticles,and the feasibility of PEG-Na Gd F₄ nanoparticles as magnetic resonance imaging contrast agent was verified.（2）A global metabolomics analysis based on UPLC-ESI-QTOF/MS was established to study the overall effects and mechanisms of Na Gd F₄ and PEG-Na Gd F₄ nano-scale contrast agents in rats.Results showed that through PEG modification,gadolinium-based nano-scale contrast agent reduced renal toxicity,reduced the influence on pyrimidine and purine metabolism,and also reduced the inflammatory response of the body to some extent,and possessed good biocompatibility.（3）A metabolomics approach based on UPLC-ESI-QTOF/MS was used to evaluate the effects of different doses of PEG-Na Gd F₄ nano-scale constract in rats.Results showed that the effect of the PEG-Na Gd F₄ nano-scale contrast agent on rats was dose-dependent.The intake of high-dose PEG-Na Gd F₄ nano-scale contrast agent would induce inflammation and renal injury in a short time,while the medium-dose and low-dose PEG-Na Gd F₄ nano-scale contrast agents had fewer effects on rats.Combined with in vivo and in vitro imaging results,medium-dose PEG-Na Gd F₄ could be used as a high-performance and safe nano-scale contrast agent in the biomedical field.