Gold nanoparticles change 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 the tumor microenvironment. Understanding how AuNPs alter sEV attributes is critical in antitumor medication design. In this study, mouse embryonic stem cells (mESCs) were treated with three sizes of AuNPs (i.e.5 nm AuNPs, 20 nm AuNPs, and 80 nm AuNPs) to obtain sEVs (i.e.sEV-5, sEV-20, and sEV-80), which were characterized from the biophysical and proteomic aspects. When compared with the control (sEV-ctrl), sEV-5 possessed relatively higher rigidity, and a 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 revealed for the first time 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.