title: Size-dependent cytotoxicity of Fe3O4 nanoparticles induced by biphasic regulation of oxidative stress in different human hepatoma cells.
abstract: The application of Fe3O4 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 Fe3O4 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 Fe3O4 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 Fe3O4 NPs exhibited negligible cytotoxicity and 9 nm Fe3O4 NPs affected cytotoxicity via cellular mitochondrial dysfunction and by inducing necrosis mediated through the mitochondria-dependent intracellular reactive oxygen species generation. Meanwhile, 14 nm Fe3O4 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 Fe3O4 NPs-induced cytotoxicity. We anticipate that this study will provide different insights into the cytotoxicity mechanism of Fe3O4 NPs, so as to make them safer to use in clinical application.
authors.affiliation: Central Laboratory; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute.
authors.forename: Yuexia
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Dejun
authors.initials: D
authors.lastname: Liu
authors.affiliation: Central Laboratory.
authors.forename: Chenlei
authors.initials: C
authors.lastname: Cai
authors.affiliation: Central Laboratory.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Central Laboratory.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Central Laboratory.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Central Laboratory; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute.
authors.forename: Huili
authors.initials: H
authors.lastname: Dai
authors.affiliation: Central Laboratory; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute.
authors.forename: Xianming
authors.initials: X
authors.lastname: Kong
authors.affiliation: Central Laboratory; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute.
authors.forename: Peifeng
authors.initials: P
authors.lastname: Liu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D058185:Magnetite Nanoparticles; D017382:Reactive Oxygen Species; D007770:L-Lactate Dehydrogenase
keywords: cytotoxicity; hepatoma cells; mechanism; nanoparticles; oxidative stress