Investigating the Biological Effect of Multidimensional Ti₃C₂ (MXene)-Based Nanomaterials through a Metabolomics Approach: a Multidimensional-Determined Alteration in Energy Metabolism

Multidimensional Ti3C2 (MXene)-based nanomaterials (m-MBNs, including nanosheets and quantum dots (QDs)) are vitally important transition-metal carbides or carbonitrides with dramatic photothermal activity in cancer therapy in animal models and display potential prospects for practical application. However, detailed bioinformation on multidimensional-induced variations in biocompatibility, metabolic processes, and mechanisms is insufficient. Metabolomics profiling has provided a distinguished alternative with massive bioinformation, which has shed light on the biological response of an organism under exogenous stimuli at the molecular level. In this work, m-MBNs were selected to interact with human umbilical vein endothelial cells (HUVECs), among which a metabolomics approach was applied to explore the changes in the HUVECs metabolome. The spatial distribution of metabolites was screened by desorption electrospray ionization-mass spectrometry imaging (DESI-MSI). The results revealed that nonobvious acute cytotoxicity was observed by cell proliferation and apoptosis assays. Comparatively, m-MBNs induced changes in the energy metabolism-related cellular events of HUVECs, while MXene QDs induced significant variation in cell metabolism, which was correlated with the multidimensional-determined mitochondria dysfunction. This work has the potential to evaluate metabolomic changes as a result of exposure to m-MBNs for assessing the biological effect of nanomaterials at the micro level. Moreover, such metabolomics-based profiling could also provide a biological forward expectation of these nanomaterials in future biomedical applications.