Source: abbottec Life Science
Multidimensional Ti3C2 (mxene) - based nanomaterials (m-mbns, including nanosheets and quantum dots (QDs)) are extremely important transition metal carbides or carbonitrides, which have significant photothermal activity in cancer treatment of animal models and show potential practical application prospects. However, detailed biological information on the changes in biocompatibility, metabolic processes and mechanisms induced by multidimensional mxene is scarce. Metabolomics combined with lipidomics analysis technology provides an alternative with a large amount of biological information, which reveals the biological response of organisms under exogenous stimuli at the molecular level.
Zhang Dingkun, assistant researcher of West China Hospital of Sichuan University (Laboratory of clinical proteomics and metabolomics, Institute of systematic Genetics) Associate researcher Gong Meng published a research paper entitled "investigating the biological effect of multidimensional Ti3C2 (mxene) - based nanomaterials through a metabolomics combined lipidomics approach: a multidimensional determined alternation in energy metabolism" on the international academic journal chemistry of materials. This research revealed the new mechanism of regulation of multidimensional mxene at the metabolomics level.
The researchers selected m-mbns to interact with human umbilical vein endothelial cells (HUVECs), and used metabolomics and lipidomics to explore the metabolome of HUVECs. The results showed that m-mbns induced changes in the biological behaviors related to energy metabolism of HUVECs, while mxene QDs induced significant changes in cell metabolism (Fig. 1-4), which was related to multidimensional induced mitochondrial dysfunction (Fig. 5). These metabolomic results can broaden the research field of biological effects of m-mbns, and further promote the innovation, material improvement and technology improvement in this research field.
Fig. 1 flow of m-mbns related cell experiments and omics research. Including m-mbns characterization, m-mbns-huvecs interaction, metabolomics analysis, lipidomics analysis, data statistical analysis, desi-msi analysis and biological verification. This process establishes a reasonable model for the effective analysis of metabolites and the evaluation of nanotoxicity of m-mbn.
Fig. 2 Changes of cell metabolomics under the intervention of m-mbns. Among the 56 differential metabolites (including organic acids, amino acids, fatty acids, sugars, etc.) and the corresponding metabolic pathways, the cellular pathways related to energy metabolism (including glycolysis, TCA cycle, pentose phosphate pathway (PPP) and fatty acid biosynthesis) play a dominant role in the "m-mbns-cell" interaction. This interaction also indicates that the sample related metabolites and metabolic pathways interfered by mxene QDs are more affected due to endocytosis, while the interference generated by mxene nanosheets is relatively weak.
Fig. 3 changes of cell lipidomics under the intervention of m-mbns. It was observed that the lipid group was also significantly disturbed. The mxene QD intervention process induced lipid increase, including phospholipids, lysophospholipids, glycerides and cholesterol esters, and had a more complex relationship between lipids, while the mxene nanosheet intervention process was relatively weak, indicating that the mxene QD induced lipid molecular changes and lipid metabolism were more intense.
Fig. 4 spatial metabolomic changes under the intervention of m-mbns. In order to further confirm the above results of metabolomics combined with lipidomics analysis, the authors collected and observed the molecular images of frozen sections of lung, kidney and liver, and studied the mice with mxene nanosheets intervention and mxene QDs intervention by desi-msi. Desi-msi is composed of power supply, solvent, capillary, free moving sample stage and MS inlet, which can realize the spatial distribution test of various metabolites.
Fig. 5 m-mbns induced mitochondrial dysfunction in cells. Based on the above results of metabolomics and lipidomics, the authors speculate that the changes in cellular energy metabolism (including glycolysis, PPP, TCA cycle and fatty acid biosynthesis) induced by m-mbns are closely related to mitochondrial dysfunction.
In summary, this study used metabolomics combined with lipidomics to explore the multidimensional induced biological effects of m-mbns on HUVECs. The results showed that the intervention of m-mbns could induce changes in energy metabolism, such as inhibiting TCA cycle and enhancing glycolysis. At the same time, the authors also found that the metabolic process was related to the spatial dimension of mxene, in which mxene QDs intervention focused on PPP, oxidative phosphorylation, amino acid metabolism, pyrimidine metabolism and lipid biosynthesis, while mxene nanosheets intervention focused on fatty acid biosynthesis. In contrast, mxene QDs can penetrate cell membranes and lead to more severe mitochondrial dysfunction and produce more ROS, while mxene nanosheets focus on indirect production.
According to the above results, the biological effects of m-mbns on HUVECs are described as follows: (I) m-mbns-cell interaction, (II) m-mbns-induced mitochondrial dysfunction, (III) inhibition of TCA cycle and enhancement of glycolysis for energy compensation. The above findings also indicate that the changes in energy metabolism in HUVECs need to be considered as potential chronic side effects in the further application of m-mbns in biological models. In conclusion, the authors believe that this new metabolomics combined with lipidomics technology can well carry out the research on the biological effects of multidimensional nanomaterials at the molecular level, and further guide the innovation of research fields, material modification and technical improvement.
The research work:
one
It is the first time to investigate the biosafety of mxene QD based on metabolomics and lipidomics;
two
It is the first time to study the changes of metabolome and lipidome levels induced by multidimensional mxene;
three
The new molecular mechanism of m-mbns inducing energy metabolism and mitochondrial dysfunction was revealed from the omics level.
Sincere thanks to Zhang Dingkun, Assistant Researcher
（ zhangdk14@outlook.com ）
For the editing and proofreading of this article, Mr. Zhang is very happy to communicate and learn with the researchers.
Gong Meng, associate researcher of West China Hospital of Sichuan University (Laboratory of clinical proteomics and metabolomics, Institute of systematic Genetics), is the corresponding author of this paper. Zhang Dingkun, assistant researcher of West China Hospital of Sichuan University (Laboratory of clinical proteomics and metabolomics, Institute of systematic Genetics), was the first author of the paper. This research work was supported by the National Natural Science Foundation of China and other projects.
Journal: Chemistry of materials
Impact factor: 9.811
Customer unit:
West China Hospital of Sichuan University (Laboratory of clinical proteomics and metabolomics, Institute of systematic Genetics)
Author:
Zhang Dingkun, assistant researcher, West China Hospital, Sichuan University (Laboratory of clinical proteomics and metabolomics, Institute of systematic Genetics)
Corresponding author:
Gong Meng, associate researcher, West China Hospital, Sichuan University (Laboratory of clinical proteomics and metabolomics, Institute of systematic Genetics)
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Reference
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Zhang, D.; Zheng, W.; Li, X.; Li, A.; Gong, M., Investigating the effect of Ti3C2 (MXene) nanosheet on human umbilical vein endothelial cells via a combined untargeted and targeted metabolomics approach. Carbon 2021, 178, 810-821.
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