Size-dependent cytotoxicity of Fe ₃O ₄ nanoparticles induced by biphasic regulation of oxidative stress in different human hepatoma cells

Abstract

The application of Fe ₃O ₄ nanoparticles (NPs) has made great progress in the diagnosis of disease and in the drug delivery system for cancer therapy, but the relative mechanisms of potential toxicity induced by Fe ₃O ₄ have not kept pace with its development in the application, which has hampered its further clinical application. In this article, we used two kinds of human hepatoma cell lines, SK-Hep-1 and Hep3B, to investigate the cytotoxic effects and the involved mechanisms of small Fe ₃O ₄ NPs with different diameters (6 nm, 9 nm, and 14 nm). Results showed that the size of NPs effectively influences the cytotoxicity of hepatoma cells: 6 nm Fe ₃O ₄ NPs exhibited negligible cytotoxicity and 9 nm Fe ₃O ₄ NPs affected cytotoxicity via cellular mitochondrial dysfunction and by inducing necrosis mediated through the mitochondria-dependent intracellular reactive oxygen species generation. Meanwhile, 14 nm Fe ₃O ₄ NPs induced cytotoxicity by impairing the integrity of plasma membrane and promoting massive lactate dehydrogenase leakage. These results explain the detailed mechanism of different diameters of small Fe ₃O ₄ NPs-induced cytotoxicity. We anticipate that this study will provide different insights into the cytotoxicity mechanism of Fe ₃O ₄ NPs, so as to make them safer to use in clinical application.