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

• Published in: Analyst (London) Vol. 149; no. 4; pp. 1169 - 1178
• Main Authors: Xu, Chen, Sun, Jie, Zhang, Chenhao, Yang, Lu, Kan, Hong, Zhang, Daguang, Xue, Guan, Dong, Kai
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 12.02.2024
• Subjects: Biocompatibility; Biomarkers; Containment of Biohazards; Contrast agents; Contrast Media - chemistry; Contrast Media - toxicity; Gadolinium; Gadolinium - chemistry; High performance liquid chromatography; Inflammatory response; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Mass spectrometry; Metabolism; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - toxicity; Quadrupoles; Reagents
• ISSN: 0003-2654; 1364-5528
• DOI: 10.1039/d3an01641b

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, NaGdF 4 and PEG-NaGdF 4 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 NaGdF 4 group than those in the PEG-NaGdF 4 group. Careful analysis of these metabolic biomarkers and pathways suggested that NaGdF 4 nanoparticles induced disturbance of pyrimidine and purine metabolism, inflammatory response, and kidney injury to a certain extent compared with PEG-NaGdF 4 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. We employed an ultra-high performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry-based metabolomics approach to investigate the potential toxicity of Gd-based nanoparticle MRI contrast agents.