SILAC-based quantitative proteomics identifies size-dependent molecular mechanisms involved in silver nanoparticles-induced toxicity

Silver nanoparticles are currently one of the most widely used metallic nanoparticles. Due to their antibacterial properties, they are applied in textiles, house-holds items, and medical devices, among many other products. Understanding the potential toxicity associated with silver nanoparticles and the differential effect that nanoparticles of different size might induce is crucial, due to the increasing human and environmental exposure to this type of nanoparticles. In this work, we explored the different biomolecular mechanisms underlying the toxicity of silver nanoparticles in a size-dependent manner. Quantitative proteomic analysis of hepatic cells exposed to 10 and 60 nm silver nanoparticles demonstrated the alteration of a different set of proteins depending on the particle size. We demonstrated that while 10 nm silver nanoparticles induce nucleolar stress and ribosome biogenesis halt, both types of nanoparticles induce DNA damage and oxidative stress but through different pathways. In addition, both types of nanoparticles also affected cell proliferation, disrupted the cell cycle and ultimately, induced apoptosis. The alteration of different cellular mechanisms in a size-dependent manner, have relevant implications not only from a toxicity point of view, but also for the potential applications of silver nanoparticles.