Multiparametric cytotoxicity profiling reveals cell-line and ligand-dependent toxicity for pegylated gold nanoparticles (AuNP-PEG)

The highly tunable surface chemistry of gold nanoparticles (AuNPs) make them ideal candidates for cancer treatments. Modification of AuNP surface chemistry creates linkage points for different surface coatings whose chemical structure regulates AuNP interactions with cells and thus plays a key role in AuNP cytotoxicity. This study looked at AuNPs functionalized with three polyethylene glycol (PEG) coatings, differing in end group functionality: PEG methyl terminated thiol (PEGCH3), PEG amine terminated thiol (PEGNH2), and PEG carboxylic acid terminated thiol (PEGCOOH). Cytotoxic effects were compared across three cell lines: Human embryonic kidney (HEK293T/17), prostate cancer (PC-3), and ovarian cancer (SKOV3). Biochemical assays measured the effect AuNPs elicit on the ability of single cells to form colonies, metabolize thiazolyl blue tetrazolium bromide (MTT), or produce reactive oxygen species (ROS) using 2',7’-dichlorofluorescein. Overall, AuNP-PEG particles were minimally toxic. HEK293T/17 colony formation was significantly decreased with all but PEGCOOH particle types, and PEGNH2 treatments significantly decreased colony formation for all three tested cell lines. ROS production was significantly increased when treated with 100 μg mL-1 AuNP PEGNH2 in all three cell lines, with PEGCH3 also showing increased ROS in PC-3 cells. PEGCH3 reduced metabolic function (MTT metabolism) in only SKOV3 cells, while PEGCOOH was toxic to HEK293T/17 cells at 100 μg mL-1. These results suggest that differing end group chemistry leads to modest cytotoxic profiles for each AuNP that are cell line and coating dependent. Elucidation of AuNP mechanisms of toxicity is a critical step in the evaluation of the future therapeutic potential for these particles.