Phospholipid-Gold Nanorods Induce Energy Crisis in MCF-7 Cells: Cytotoxicity Evaluation Using LC-MS-Based Metabolomics Approach

Dahabiyeh, Lina A.; Mahmoud, Nouf N.; Al-Natour, Mohammad A.; Safo, Laudina; Kim, Dong-Hyun; Khalil, Enam A.; Abu-Dahab, Rana

Abstract

Phospholipid-modified gold nanorods (phospholipid-GNRs) have demonstrated drastic cytotoxicity towards MCF-7 breast cancer cells compared to polyethylene glycol-coated GNRs (PEG-GNRs). In this study, the mechanism of cytotoxicity of phospholipid-GNRs towards MCF-7 cells was investigated using mass spectrometry-based global metabolic profiling and compared to PEGylated counterparts. The results showed that when compared to PEG-GNRs, phospholipid-GNRs induced significant and more pronounced impact on the metabolic profile of MCF-7 cells. Phospholipid-GNRs significantly decreased the levels of metabolic intermediates and end-products associated with cellular energy metabolisms resulting in dysfunction in TCA cycle, a reduction in glycolytic activity, and imbalance of the redox state. Additionally, phospholipid-GNRs disrupted several metabolism pathways essential for the normal growth and proliferation of cancer cells including impairment in purine, pyrimidine, and glutathione metabolisms accompanied by lower amino acid pools. On the other hand, the effects of PEG-GNRs were limited to alteration of glycolysis and pyrimidine metabolism. The current work shed light on the importance of metabolomics as a valuable analytical approach to explore the molecular effects of GNRs with different surface chemistry on cancer cell and highlights metabolic targets that might serve as promising treatment strategy in cancer.

Citation

Dahabiyeh, L. A., Mahmoud, N. N., Al-Natour, M. A., Safo, L., Kim, D.-H., Khalil, E. A., & Abu-Dahab, R. (2021). Phospholipid-Gold Nanorods Induce Energy Crisis in MCF-7 Cells: Cytotoxicity Evaluation Using LC-MS-Based Metabolomics Approach. Biomolecules, 11(3), Article 364. https://doi.org/10.3390/biom11030364

• Journal Article Type: Article
• Acceptance Date: Feb 22, 2021
• Online Publication Date: Feb 27, 2021
• Publication Date: 2021-03
• Deposit Date: Jul 22, 2024
• Publicly Available Date: Jul 24, 2024
• Journal: Biomolecules
• Electronic ISSN: 2218-273X
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 3
• Article Number: 364
• DOI: https://doi.org/10.3390/biom11030364
• Public URL: https://nottingham-repository.worktribe.com/output/5377021
• Publisher URL: https://www.mdpi.com/2218-273X/11/3/364