Silver Nanoparticle Enhances Secretion of Exosomes in SH-SY5Y Cells: Potential Therapeutic Strategy for Human Neuroblastoma Cancer

Background: Exosomes-a subset of extracellular vesicles (EVs)-are secreted by virtually all cells, including human neuroblastoma cancer (SH-SY5Y) cells, into bodily fluids. Oxidative stress is critically involved in exosome biogenesis and release. Silver nanoparticles (AgNPs) induce cytotoxicity, oxidative stress, and apoptosis in cancer and non-cancer cells. Methods: Here, we studied whether AgNPs-induced oxidative stress could enhance exosome biogenesis and release under low serum conditions in the presence of AgNPs. Although several studies have reported various mechanisms that contribute to EV biogenesis and release from cells, none exists on the involvement of external stimuli by controlling acetylcholinesterase (AChE) and neutral-sphingomyelinase (n-SMase) activities, total protein concentration of exosomes, and exosome count. Results: Owing to cytotoxic and oxidative stresses, AgNPs-treated cells and exosome release were significantly facilitated, which strongly correlated with the AgNPs-induced oxidative stress. Moreover, the expression levels of some important exosome biomarkers were found to be significant under oxidative stress conditions. N-acetylcysteine prevented oxidative stress-induced exosome biogenesis and release. Furthermore, we identified the involvement of the ceramide pathway in exosome functions by inhibiting AChE and n-SMase activities, and exosome protein/counts. These data contribute to the understanding of how AgNPs and intracellular molecular pathways affect exosome biogenesis and release in SH-SY5Y cells. Conclusion: To the best of our knowledge, this is the first study showing that AgNPs stimulate exosome biogenesis and release by inducing oxidative stress and ceramide pathways.