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

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.

A Metabolic Pattern in Healthy Subjects Given a Single Dose of Metformin: A Metabolomics Approach

“…Metabolomics is the comprehensive analysis of a set of small molecules (i.e., amino acids, lipids, and carbohydrates), referred to as metabolites within cells, biofluids, tissues, or organisms. It is a powerful analytical tool that is widely used to provide rich mechanistic information on drugs, and aid in identifying potential biomarkers that can be used to monitor the efficacy of drug therapies (Balashova et al, 2018;Jacob et al, 2019;Dahabiyeh et al, 2021). Pharmacometabolomics is an effective approach to capture the metabolic signatures linked to drug exposure and, therefore, improves the understanding of their underlying mechanisms of actions and allows individual differences recognition and drug toxicity prediction (Adam et al, 2016;Malkawi et al, 2018;Dahabiyeh et al, 2020).…”

The Effect of Surface-Modified Gold Nanorods on the Early Stage of Embryonic Development and Angiogenesis: Insight into the Molecular Pathways

“…We demonstrated in our previous work the cytotoxicity of GNR decorated with a phospholipid moiety (GNR (A)) towards a panel of breast cancer cell lines and their modulation effect on several regulatory factors involved in cellular apoptosis and energy metabolism [24][25][26]. Furthermore, GNR-decorated with a cholesterol moiety (GNR (B)) were utilized as an efficient nanocarrier for several drugs with relatively low cytotoxicity towards normal healthy cells [27,28,37].…”

“…Previous reports indicate that biological responses towards GNP, including cytotoxicity, cellular internalization, and bio-distribution, are strongly correlated with GNP's shape, size, and surface chemistry [21,22]. Our recent work displayed that the interaction of gold nanorods (GNR) with human skin or cancerous cells is considerably correlated with the nanoparticles' surface modification; GNR conjugated with polyethylene glycol (PEG)-phospholipid moiety exhibited enhanced uptake into human skin tissue [23] and breast cancer cell lines, promoting several apoptotic pathways [24,25], and modulating the production of metabolites responsible for cellular energy metabolism [26]. On the other hand, GNR conjugated with a cholesterol moiety was successfully utilized as a nanocarrier to deliver anti-cancer and antifungal agents [27,28].…”

Lipids Alterations Associated with Metformin in Healthy Subjects: An Investigation Using Mass Spectrometry Shotgun Approach

“…The expanding development of omics approaches has allowed for a holistic view of various therapeutics’ molecular mechanisms and provided a promising strategy to monitor drugs and innovative compounds [ 24 , 25 ]. Lipids are directly exposed to the biochemical changes linked to pathological processes or drug treatment.…”