A metabolomics investigation of a nanogold drug vehicle on experimental animals

Abstract

Nanotechnology has increasingly received attention the last few decades and the term refers to the categories of applied science and technology, where the combining key subject is the study of matter in scales of 1 to 100 nm and the designing of devices within that size range. Gold nanoparticles have especially drawn massive scientific attention; the reasons being that these particles exhibit high chemical stability and unique optical properties. Furthermore, gold nanoparticles can be easily synthesised and modified, while providing great potential for a drug delivery vehicle. There is however a gap in current research with regards to the safety and effect of these particles, especially in the field of metabolomics. This study thus aimed to provide a more comprehensive view of the effect of gold nanoparticles on the metabolome, by implementing an animal model. Two groups of Sprague-Dawley rats were monitored: one control group and one treatment group. The control group received a 0.9% saline solution and the treatment group received a solution of gold nanoparticles dispersed in citrate (90μg/500μl). Urine was collected at different time points over the course of 48 hours. The study utilised three different, but effective, platforms popular within the field of metabolomics, namely 1-dimensional Nuclear Magnetic Resonance (1H-NMR) spectroscopy, Liquid Chromatography Mass Spectrometry and Gas-chromatography Time-Of-Flight Mass Spectrometry (GC-TOF/MS). Urine samples were analysed via these platforms using both untargeted and targeted metabolomics approaches, investigating an array of metabolites (including amino acids, acylcarnitines and organic acids). The data was subjected to bio-statistical analysis to identify the relevant changes in metabolite levels and produce a full list of significant compounds affected by the intervention of gold nanoparticles. The significant metabolites brought forth evidence of possible perturbation within the pathways of energy metabolism as well as carbon- and amino acid metabolism. The results were found to produce a similar profile to that of many heavy metals, in the sense that binding with sulphur-containing molecules occurred readily and consequently inhibiting the function of several proteins and enzymes. The most prominent findings were linked to the enzyme dehydrogenase family and the thiol-rich compounds of the amino acid pathways, which are often associated with a phenotype similar to heavy metal poisoning. Therefore, it is reasoned as is in the case of other heavy metals, that gold (even in nanoform) possesses a high affinity for sulphur-containing compounds and will promptly replace these bonds, by displacing the original ion.