Ultrasmall Fe 3 O 4 nanoparticles induce S-phase arrest and inhibit cancer cells proliferation

The ultrasmall nanoparticles easily lead to a more seriously response than larger nanoparticles because of their physicochemical features. It is essential to understand their cytotoxicity effects for their further application. Here, we used ultrasmall 9 nm Fe 3 O 4 NPs to explore its cytotoxicity mechanism on breast cancer cells. We demonstrated 9 nm Fe 3 O 4 NPswas effectively internalized into cells and located in nucleus, subsequently, it inhibited DNA synthesis through inducing S-phase arrest.Moreover, 9 nm Fe 3 O 4 NPs induced ROS production and oxidative damage by disturbing the expression of antioxidant-related genes (HMOX-1, GCLC and GCLM), which resulted in the enhancement of cells apoptosis and inhibition of cell proliferation, suggesting its potential to be used as therapeutic drug.