Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress

Abstract

Iron oxide nanoparticles with unique magnetic properties have a high potential for use in several biomedical, bioengineering and in vivo applications, including tissue repair, magnetic resonance imaging, immunoassay, drug delivery, detoxification of biologic fluids, cell sorting, and hyperthermia. Although various surface modifications are being done for making these nonbiodegradable nanoparticles more biocompatible, their toxic potential is still a major concern. The current in vitro study of the interaction of superparamagnetic iron oxide nanoparticles of mean diameter 30 nm coated with Tween 80 and murine macrophage (J774) cells was undertaken to evaluate the dose-and time-dependent toxic potential, as well as investigate the role of oxidative stress in the toxicity. A 15-30 nm size range of spherical nanoparticles were characterized by transmission electron microscopy and zeta sizer. MTT assay showed .95% viability of cells in lower concentrations (25-200 µg/mL) and up to three hours of exposure, whereas at higher concentrations (300-500 µg/mL) and prolonged (six hours) exposure viability reduced to 55%-65%. Necrosis-apoptosis assay by propidium iodide and Hoechst-33342 staining revealed loss of the majority of the cells by apoptosis. H 2 DCFDDA assay to quantify generation of intracellular reactive oxygen species (ROS) indicated that exposure to a higher concentration of nanoparticles resulted in enhanced ROS generation, leading to cell injury and death. The cell membrane injury induced by nanoparticles studied using the lactate dehydrogenase assay, showed both concentration-and time-dependent damage. Thus, this study concluded that use of a low optimum concentration of superparamagnetic iron oxide nanoparticles is important for avoidance of oxidative stress-induced cell injury and death.

Uptake and Transport of Superparamagnetic Iron Oxide Nanoparticles through Human Brain Capillary Endothelial Cells

“…Exposure to SPIONs and a Magnetic Force Does Not Lead to Cytotoxicity of the BCECs. SPIONs have been shown to induce oxidative stress, 12 and therefore, we wanted to test the cell viability within the time frame of this study. It is also known that cells of different origin react differently upon exposure to SPIONs; this phenomenon is called the "cell vision".…”

“…11 Typically, the SPIONs have a mean diameter of 50−100 nm, 11 and their iron oxide core exerts low toxicity, as it is gradually degraded to Fe 3+ in the body and enters the pool of body iron; 11 e.g., SPIONs induce oxidative stress only in murine macrophage (J774) cells at doses higher than 100 μg/mL. 12 The magnetic core of SPIONs can be coated with lipophilic fluorescent dyes for visual detection. Furthermore, the particles can be protected by biocompatible polymeric shell materials like dextran, polysorbate, or starch or coated by phospholipids or polyethylene glycol (PEG) to prolong their presence within the circulation because of a lower level of recognition of the particles by the reticulo endothelial system.…”

Long term biotransformation and toxicity of dimercaptosuccinic acid-coated magnetic nanoparticles support their use in biomedical applications

“…We analyzed the possible cytotoxic effects of DMSA-MNP on NCTC 1469 hepatic cells. As most previous studies of MNP cytotoxicity were conducted at low nanoparticle concentrations, or incubation times potentially too short to determine all possible toxic effects on cultured cells [28], we used iron concentrations up to 0.5 mg/ml, and incubation times up to 72 h.…”

In vitro biological effects of magnetic nanoparticles

“…It is reported that toxicity of SPIONs with a mean size of 30 nm coated with Tween 80 surfactant in murine macrophage (J774) cells was found to be due to induction of oxidative stress and subsequent apoptosis. The intracellular ROS generation evaluated by a H 2 DCFDDA assay showed both concentration-and time-dependent, and the enhanced ROS production led to cell injury and death [55].…”

“…Although some studies have not found the direct correlation between toxicity and ROS production induced by MNPs [49], most studies concluded that nanoparticles can be toxic, not only affecting cells in a direct way, but also indirectly by the induction of excess ROS [54,55]. It is reported that toxicity of SPIONs with a mean size of 30 nm coated with Tween 80 surfactant in murine macrophage (J774) cells was found to be due to induction of oxidative stress and subsequent apoptosis.…”