Despite the increasing application of gold nanoparticles, there has been little assessment of biological system toxicity to evaluate their potential impact on human health. In this study, the human hepatoma cell line (Hep G2) was used in a metabolomics approach to study the effects of shape, time, and dose of gold nanorods (GNRs). Using optimized parameters for chromatography and mass spectrometry, the metabolites detected by GC-MS were processed with MS DIAL and identified with Fiehnlib. Key metabolic pathways affected by GNRs were identified by endo-metabolic profiling of cells mixed with GNRs of varying shape while varying the dose and time of exposure. The shape of GNRs affected cytotoxicity, and short GNR (GNR-S) triggered disorder of cell metabolism. High concentrations of GNRs caused more significant toxicity. The cytotoxicity and bioTEM results illustrated that the mitochondria toxicity, as the main cytotoxicity of GNRs, caused declining cytoprotective ability. The mitochondrial dysfunction disrupted alanine, aspartate, glutamate, arginine, and proline metabolism, with amino acid synthesis generally downregulated. However, the efflux function of cells can exclude GNRs extracellularly within 24 h, resulting in reduced cell mitochondrial metabolic toxicity and allowing metabolic disorders to recover to normal function.
Keywords: gold nanorods; metabolomics; mitochondria toxicity; nanotoxicity.