Silver nanoparticles exposure induces developmental neurotoxicity in hiPSC-derived cerebral organoids

Silver nanoparticles (AgNPs) are used in various research fields. Although the neurotoxicity of AgNPs has been explored in animal models and 2D cell-culture models, including human stem cells, these models cannot accurately mimic the development of the human brain. Therefore, the potential mechanisms of AgNPs-induced developmental neurotoxicity in humans are still largely unclear. In this study, cerebral organoids derived from induced pluripotent stem cells were treated with 0.1 mu g/mL or 0.5 mu g/mL AgNPs for 7 days. At the low concentration (0.1 mu g/mL), AgNPs increased the cell proliferation and inhibited the neural apoptosis in the organoids, but impaired the cilium assembly and elongation, which may perturb the cell cycle and induce abnormal cerebral-organoid growth. Conversely, at the high concentration (0.5 mu g/mL), AgNPs significantly inhibited cell proliferation and induced apoptosis in cerebral organoids. High-concentration AgNPs reduced the expression and co-localization of the cytoskeleton proteins F-actin, myosin, and tubulin, thereby perturbing neurite growth. In conclusion, AgNPs exposure induces developmental neurotoxic effects in cerebral organoids and is thus a potential congenital risk factor.