Investigating the effect of Ti3C2 (MXene) nanosheet on human umbilical vein endothelial cells via a combined untargeted and targeted metabolomics approach

Ti3C2 is the first member of two-dimensional (2D) transition metal carbide or carbonitride (MXene) with excellent photothermal effect in disease treatment on an animal model, which shows a potential prospect on clinical application. However, in-depth details on the biosafety of MXene were insufficient. Metabolomics approach has offered an excellent alternative with numerous bioinformation, which can demonstrate the response of an organism to external stimuli at the molecular level. In this study, two different concentrations (100 and 500 mg/L) of MXene were used to treat human umbilical vein endothelial cells (HUVECs), and under both conditions, no obvious acute cytotoxicity was observed by cell proliferation and apoptosis measurement. We used a platform combining LC-MS/MS, GC-MS, and bioinformatics to analyze the changes of HUVECs metabolome after treatment with different concentrations of MXene, and the results indicated that —high concentrations (500 mg/L) of MXene can cause significant changes in the energy metabolism of HUVECs, showing obvious inhibition of tricarboxylic acid (TCA) cycle with the enhancement of glycolysis, fatty acid biosynthesis, and lipid accumulation, which are closely related to the functional disorder of mitochondria. The metabolomics results of the novel MXene-cell system extend the knowledge on the biological effect of MXene, possibly enabling technological innovations and material modifications.