Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress - PubMed (original) (raw)

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

Saba Naqvi et al. Int J Nanomedicine. 2010.

Retraction in

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. H₂DCFDDA 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.

Keywords: J774 cell line; MTT assay; cytotoxicity; superparamagnetic iron oxide nanoparticles.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Zeta sizer picture of superparamagnetic iron oxide nanoparticles showing size distribution in aqueous medium.

Figure 2

Figure 2

Transmission electron microscopy of superparamagnetic iron oxide nanoparticles.

Figure 3

Figure 3

The effects of superparamagnetic iron oxide nanoparticles on cell proliferation and viability of J774 cells as determined by MTT assay. Concentration-dependent cytotoxic effects of nanoparticles evaluated after three and six hours of incubation. Results are represented as means ± standard error of the mean. **Note: ***Significant difference from control (P < 0.05).

Figure 4

Figure 4

H2DCFDDA assay for intracellular reactive oxygen species with superparamagnetic iron oxide nanoparticles. A) Control and B) at concentration of 500 μg/mL.

Figure 5

Figure 5

Apoptosis of J774 cells incubated with 500 μg/mL superparamagnetic iron oxide nanoparticles. A) Control and B) at six hours. The bright blue nuclei represent apoptosis stained with fluorescent dye Hoechst-33342.

Figure 6

Figure 6

Concentration-dependent membrane damage as determined by lactate dehydrogenase leakage from J774 cell lines (2 × 104 cells/mL) incubated with superparamagnetic iron oxide nanoparticles for six hours.

Figure 7

Figure 7

Transmission electron microscopy photograph of J774 cells showing superparamagnetic iron oxide nanoparticles in the cytosol as electron-dense particles following incubation for six hours with 200 μg/mL × 80,000.

Similar articles

Cited by

References

    1. Lubbe AS, Alexiou C, Bergemann C. Clinical applications of magnetic drug targeting. J Surg Res. 2001;95(2):200–206. - PubMed
    1. Polyak B, Friedman G. Magnetic targeting for site-specific drug delivery: Applications and clinical potential. Expert Opin Drug Deliv. 2009;6(1):53–70. - PubMed
    1. Shi J, Gider S, Babcock K, et al. Magnetic clusters in molecular beams, metals, and semiconductors. Science. 1996;271:937–941.
    1. Sastry M. Moving nanoparticles around: Phase-transfer processes in nanomaterials synthesis. In: Rao CNR, Achim Muller HC, Cheetham AK, editors. The Chemistry of Nanomaterials. Weinheim, Germany: Wiley-VCH, Verlag GmbH and Co. KGaA; 2005.
    1. Lubbe AS, Bergemann C, Riess H, et al. Clinical experiences with magnetic drug targeting: A phase I study with 4′-epidoxorubicin in 14 patients with advanced solid tumors. Cancer Res. 1996;56(20):4686–4693. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources