Metabolomics-derived biomarkers for biosafety assessment of Gd-based nanoparticle magnetic resonance imaging contrast agents

Abstract

With the rapid development of nanotechnology and biomedicine, numerous gadolinium (Gd)-based nanoparticle MRI contrast agents have been widely investigated. Due to the unique physicochemical properties of nanoparticles and the complexity of biological systems, the biosafety of Gd-based nanoparticle MRI contrast agents has been paid more and more attention. Herein, for the first time, we employed an ultra-high performance liquid chromatography–electrospray ionization quadrupole time-of-flight/mass spectrometry (UPLC-ESI-QTOF/MS)-based metabolomics approach to investigate the potential toxicity of Gd-based nanoparticle MRI contrast agents. In this work, NaGdF₄ and PEG-NaGdF₄ nanoparticles were successfully constructed and selected as the representative Gd-based nanoparticle MRI contrast agents for the metabolomics analysis. Based on the results of metabolomics, more metabolic biomarkers and pathways were identified in the NaGdF₄ group than those in the PEG-NaGdF₄ group. Careful analysis of these metabolic biomarkers and pathways suggested that NaGdF₄ nanoparticles induced disturbance of pyrimidine and purine metabolism, inflammatory response, and kidney injury to a certain extent compared with PEG-NaGdF₄ nanoparticles. These results indicated that Gd-based nanoparticle contrast agents modified with PEG had better biosafety. Additionally, it was demonstrated that the discovery of characteristic metabolomics biomarkers induced by nanoparticles would provide a new approach for biosafety assessment and stimulate the development of nanomedicine.