A Comparison of the Genotoxic Effects of Gold Nanoparticles Functionalized with Seven Different Ligands in Cultured Human Hepatocellular Carcinoma Cells

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.

Glutathione-Capped Hollow Silver Nanoparticles: Optimization of Surface Plasmon Resonance, Photothermal Effect, and In Vitro and In Vivo Biocompatibility

“…Besides controlling the particle size and shell thickness, previous reports highlight that GSH capping also plays a role in cellular internalization and biocompatibility. For instance, GSH-stabilized AuNPs displayed fivefold higher cellular internalization than Tri-Na-stabilized AuNPs . Another recent report highlighted GSH-stabilized AuNPs inducing reversible DNA damage compared to Tri-Na-stabilized AuNPs, which led to irreversible DNA damage in HeLa cells .…”

“…For instance, GSH-stabilized AuNPs displayed fivefold higher cellular internalization than Tri-Na-stabilized AuNPs . Another recent report highlighted GSH-stabilized AuNPs inducing reversible DNA damage compared to Tri-Na-stabilized AuNPs, which led to irreversible DNA damage in HeLa cells . Another independent report highlighted citrate-stabilized AuNPs inducing liver inflammation compared to HEPES-stabilized AuNPs .…”

“…55 Another recent report highlighted GSH-stabilized AuNPs inducing reversible DNA damage compared to Tri-Na-stabilized AuNPs, which led to irreversible DNA damage in HeLa cells. 55 Another independent report highlighted citrate-stabilized AuNPs inducing liver inflammation compared to HEPES-stabilized AuNPs. 56 Therefore, our data and previous findings suggest that apart from impacting particle characteristics, GSH also improves cellular internalization and biocompatibility of the NPs compared to Tri-Na.…”

Advances of Antimicrobial Peptide‐Based Biomaterials for the Treatment of Bacterial Infections

“…[56] Previous studies have shown that metal-based nanoparticles have a nonspecific bacterial mechanism of action (they do not bind to specific receptors in bacterial cells), which not only makes it difficult for bacteria to develop resistance, but also broadens the range of antibacterial activity. [57] However, metal nanoparticle-based AMPs as novel antimicrobial agents for [53] Copyright 2016, American Chemical Society. B) Formation of AgNPs on PA nanofibers.…”

“…[ 56 ] Previous studies have shown that metal‐based nanoparticles have a nonspecific bacterial mechanism of action (they do not bind to specific receptors in bacterial cells), which not only makes it difficult for bacteria to develop resistance, but also broadens the range of antibacterial activity. [ 57 ] However, metal nanoparticle‐based AMPs as novel antimicrobial agents for treating bacterial infections, have not shown excellent therapeutic effects in mouse models. Compared with the rest of the previously described self‐assembled peptides, there is still a gap in the reduction of organ bacterial load and inflammatory damage.…”