Study of the effects of Au@ZIF-8 on metabolism in mouse RAW 264.7 macrophages.

Abstract

Mass spectrometry-based metabolomics plays a vital role in discovering new markers and revealing the unpredictable biological effects of external stimuli. However, the current metabolomics research on materials is still in its infancy, and in-depth research on possible toxic mechanisms is lacking. In this study, a nanocomposite of gold nanoparticles (AuNPs)-zeolite-imidazole framework-8 (ZIF-8) (Au@ZIF-8) was designed to investigate its effects on metabolism in mouse RAW 264.7 macrophages. The successful synthesis of Au@ZIF-8 was confirmed by transmission electron microscopy (TEM) and elemental analysis. The changes in the metabolic activity of mouse RAW 264.7 macrophages at different concentrations of Au@ZIF-8 and different treatment times were investigated, and their influence on the morphological changes and behavior of RAW 264.7 cells was discussed. In addition, ultrahigh-performance liquid chromatography quadrupole-orbital high-resolution mass spectrometry (UHPLC/Q-Orbitrap HRMS) was used to study the metabolic effects of Au@ZIF-8 on RAW 264.7 cells, and the results showed different metabolites being expressed at different reaction times. After 4, 8 and 24h of treatment, the differential expression of 14, 16, and 16 metabolites, respectively, was detected. Twenty-five candidate key metabolites were identified from the results of the expression patterns and metabolic pathways. These metabolites are related to glutamine metabolism, the tricarboxylic acid cycle and glycolytic metabolic pathways, which may provide insight into the treatment of diseases caused and progressed by glutamine metabolism. This study also indicates the effectiveness of high-resolution LC-MS in revealing the nanotoxicity mechanism of Au@ZIF-8.