ABSTRACT
Gold nanoparticles (GNPs) have shown great potential in diagnostic and therapeutic applications in diseases, such as cancer. Despite GNP versatility, there is conflicting data regarding the toxicity of their overall functionalization chemistry for improved biocompatibility. This study aimed to determine the possible genotoxic effects of functionalized GNPs in Human hepatocellular carcinoma (HepG2) cells. GNPs were synthesized and biofunctionalized with seven common molecules used for biomedical applications. These ligands were bovine serum albumin (BSA), poly(sodium 4-styrene sulfonate) (PSSNA), trisodium citrate (citrate), mercaptoundecanoic acid (MUA), glutathione (GSH), polyvinylpyrrolidone (PVP), and polyethylene glycol (PEG). Before in vitro genotoxicity assessment, inductively coupled plasma mass spectrometry was used to determine GNP cellular internalization quantitatively, followed by cell-based assays; WST-1 to find IC 30 and ApoPercentage for apoptotic induction time-points. The effect of the GNPs on cell growth in real-time was determined by using xCELLigence, followed by a comet assay for genotoxicity determination. The HepG2 cells experienced genotoxicity for all GNP ligands; however, they were able to initiate repair mechanisms and recover DNA damage, except for two functionalization chemistries.
ABSTRACT
Studies on the safety of gold nanoparticles (GNPs) are plentiful due to their successful application in drug delivery and treatment of diseases in trials. Cytotoxicity caused by GNPs has been studied on the physiological and biochemical level; yet, the effect of GNPs (particularly gold nano-spheres) on the metabolome of living organisms remains understudied. In this investigation, metabolomics was used to comprehensively study the metabolic alterations in HepG2 cells caused by GNPs; and to investigate the role of representative GNP coatings. GNPs were synthesized, coated and characterized before use on HepG2 cell cultures. Cells were treated for 3 h with citrate-, poly-(sodiumsterene sulfunate)-, and poly-vinylpyrrolidone (PVP)-capped GNPs, respectively. The internalization of the different GNPs and their effect on mitochondrial respiration and the metabolome were studied. Results indicated that the PVP-capped GNPs internalized more and also caused a more observable effect on the metabolome. Conversely, it was the citrate- and poly-(sodiumsterene sulfunate) coated particles that influenced ATP production in addition to the metabolomic changes. A holistic depletion of intracellular metabolites was observed regardless of GNP coating, which hints to the binding of certain metabolites to the particles.
