Abstract

Superparamagnetic iron-oxide nanoparticles (SPIONs) show great promise for multiple applications in biomedicine. While a number of studies have examined their safety profile, the toxicity of these particles on reproductive organs remains uncertain. The goal of this study was to evaluate the cytotoxicity of starch-coated, aminated, and PEGylated SPIONs on a cell line derived from Chinese Hamster ovaries (CHO-K1 cells). We evaluated the effect of particle diameter (50 and 100 nm) and polyethylene glycol (PEG) chain length (2k, 5k and 20k Da) on the cytotoxicity of SPIONs by investigating cell viability using the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. The kinetics and extent of SPION uptake by CHO-K1 cells was also studied, as well as the resulting generation of intracellular reactive oxygen species (ROS). Cell toxicity profiles of SPIONs correlated strongly with their cellular uptake kinetics, which was strongly dependent on surface properties of the particles. PEGylation caused a decrease in both uptake and cytotoxicity compared to aminated SPIONs. Interestingly, 2k Da PEG-modifed SPIONs displayed the lowest cellular uptake and cytotoxicity among all studied particles. These results emphasize the importance of surface coatings when engineering nanoparticles for biomedical applications.

Highlights

  • Iron-oxide nanoparticles, and in particular superparamagnetic iron-oxide nanoparticles (SPIONs), have gained a fair amount of attention in recent years, accounting for more than 5900 publications over the last five years (PubMed database, quick search in December 2015 with the following keywords: “iron-oxide nanoparticle”)

  • While the uptake kinetics varied between tested SPIONs, the results indicate that surface properties have a greater influence on uptake than the particle size

  • The toxicity profiles observed for the SPIONs suggest the plausibility of saturable uptake kinetics, as previously described in astrocytes [37]

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Summary

Introduction

Iron-oxide nanoparticles, and in particular superparamagnetic iron-oxide nanoparticles (SPIONs), have gained a fair amount of attention in recent years, accounting for more than 5900 publications over the last five years (PubMed database, quick search in December 2015 with the following keywords: “iron-oxide nanoparticle”). Their magnetic properties, combined with the possibilities afforded by optimization of their surface chemistry, promise potential applications in many fields, including nanomedicine [1,2,3,4]. A thorough understanding of the physicochemical parameters underlying toxicity of SPIONs on normal systems is essential, especially since repetitive administrations may be part of a diagnostic and/or treatment regimen

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