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.

Magnetic Iron Oxide Nanoparticles: Synthesis, Characterization and Functionalization for Biomedical Applications in the Central Nervous System

“…The selected literature was classified into four main groups:Methods of synthesis of IONPs [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56]Characterization of IONPs [57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,…”

“…Characterization of IONPs [57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85]…”

“…The MNPs design, particularly related to their physical and chemical properties, can be controlled to fit different biomedical applications, allowing an accurate control of their spatial, temporal, and dosage distribution [1]. The increasing interest in nanomedicine has aroused a special focus on fabrication protocols for high-performance IONPs, for obtaining not only the desired physicochemical properties, such as: Morphology, size, and structure, but also a good biocompatibility [67,68].…”

Ferrite Nanoparticles-Based Reactive Oxygen Species-Mediated Cancer Therapy

“…The size dependence of the catalytic activity of ferrite nanoparticles was further studied by Liu and colleagues. They investigated the cytotoxic effects of small Fe 3 O 4 nanoparticles with different diameters (6, 9, and 14 nm) on human hepatoma cell lines, SK-Hep-1 and Hep3B (Xie et al, 2016 ). The 9 nm Fe 3 O 4 nanoparticles mediated mitochondria-dependent intracellular ROS generation to induce cellular mitochondrial dysfunction and necrosis, while the 14 nm Fe 3 O 4 nanoparticles led to plasma membrane damage.…”

Physical and Biological Evaluation of Low-Molecular-Weight Hyaluronic Acid/Fe3O4 Nanoparticle for Targeting MCF7 Breast Cancer Cells

“…Polymers 2020, 12, x FOR PEER REVIEW 10 of 15 6 nm Fe3O4 NPs exhibited negligible cytotoxicity. However, Fe3O4 NPs with particle size larger than 9 nm may affect cytotoxicity by inducing cellular mitochondrial dysfunction or impairing the integrity of plasma membrane [41]. The particle size of the prepared Fe3O4 NPs is mainly concentrated between 4 and 6 nm, and this is the reason the Fe3O4 NPs prepared in this study showed no cytotoxic effects on cells.…”