Gold Nanoparticles Disturb Small Extracellular Vesicle Attributes of Mouse Embryonic Stem Cells

Gold nanoparticles (AuNPs) have attracted considerable interest in suppressing tumor cell migration, while small extracellular vesicles (sEVs) play an essential role in tumor metastasis by shaping tumor microenvironment. Understanding how AuNPs alter sEV attributes is critical in antitumor medication design. In this study, the mouse embryonic stem cells (mESCs) were treated with three sizes of AuNPs (i.e. 5 nm AuNP, 20 nm AuNP, 80 nm AuNP) to obtain sEVs (i.e. sEV-5, sEV-20, sEV-80), which were characterized from biophysical and proteomic aspects. When compared with the control (sEV-ctrl), sEV-5 possessed the relatively higher rigidity, and differentially-expressed protein profile. It attenuated 4T1 tumor cell proliferation and migration through inhibiting cofilin expression and extracellular regulated protein kinase (Erk) phosphorylation, which was opposite to the effect induced by sEV-ctrl. In contrast, sEV-20 and sEV-80 had negligible effects. This study firstly revealed that AuNP-5 exposure changed the biophysical properties and cellular functions of mESC-derived sEVs, providing a promising strategy for designing AuNP-based antitumor medication.