(527e) Size-Dependent Cellular Toxicity of Gold Nanoparticles on Human Embryonic Stem Cells

Increased demands for toxicological evaluations of engineered nanomaterials coincide with the accelerated pace of clinical translation and commercialization of nanomaterials. There is an urgent need to develop predictive and validated toxicological assessment methods for nanomaterials due to their unique size range, surface chemistry, and interactions with biological systems. Most cell-based nanotoxicity assessments are limited to long-lived cell lines or cancer cells. Human embryonic stem cells (hESCs) and their subsequent neural precursor differentiations provide a toolkit to study the effect of exposure to nanoparticles on neural specification. We employ gold nanoparticles (AuNPs) as model nanoparticles due to their versatile surface chemistry, ease of imaging, and tunability for transport across the blood-brain barrier. AuNPs are considered by most as nontoxic, which is consistent with the inertness of bulk gold, but some have found them toxic. This talk describes a toxicological study of AuNPs of different core sizes (1.5 nm, 4.0 nm, and 14 nm) as well as dendrimers (0.5 nm and 1.5 nm) using the hESCs. The various nanoparticles were coated with bovine serum albumin prior to their introduction to the cell culture medium. The nanoparticles were characterized by UV-vis spectroscopy, TEM, dynamic light scattering, and AFM. We found that colonies exposed to 1.5 nm AuNPs exhibited loss of cohesiveness, rounding up, and detachment suggesting ongoing cell death. The hESCs exposed to 1.5nm AuNPs did not form embryoid bodies but rather rapidly disintegrated into single cells within 48 hours of treatment. Cell death caused by 1.5nm AuNPs also occurred in the treatment hESC-derived neural precursor/progenitor cells. None of the other nanoparticles exhibited such toxic effect on the hSECs. We also found that 4.0 nm AuNPs caused a dramatic hypomethylation of the hESC DNA in only 24 hours. This work contributes a new toolkit for predicting neurotoxicity of nanoparticles that will ultimately impact consumers, patients, and manufacturing workers of products containing nanoparticles.