Superparamagnetic iron oxide nanoparticles are the only clinically approved metal oxide nanoparticles.1 Given that iron oxides magnetite (Fe3O4) and maghemite (γ-Fe2O3) occur naturally as nano-sized crystals in the Earth’s crust, it would seem that there is no intrinsic risk associated with these nanoparticles.

Magnetite nanoparticles have attracted much attention not only because of their superparamagnetic properties but also because they have been shown to have low toxicity in the human body. Currently, magnetite nanoparticles are used in a variety of biomedical applications, for example, magnetic resonance imaging, targeted delivery of drugs or genes, targeted destruction of tumor tissue through hyperthermia, magnetic transfections, iron detection, chelation therapy and tissue engineering.2

Uncoated magnetite nanoparticles have very low solubilities that can lead to precipitation and agglomeration under physiological conditions. To mediate these effects they are coated with materials such as silicon, dextran, citrate and PEGylated starch.3 The surface coating of iron oxide plays an important role in internalization effects.4

Several studies have examined the toxicity potential of several different types of magnetite nanoparticles with a range of surface coatings and have generally found low or no toxicity associated with these nanoparticles until high exposure levels (>100 mg/ml).5 The toxicity was also found to be dependent on various factors such as type of surface coating or its breakdown products, tail length, chemical composition of cell-medium, oxidation state and protein interaction.6

Exposure to magnetite particles also occurs in the environment. In one study, rat exposure to iron oxide dust was tolerated without mortality, consistent changes in body weights, food and water consumption or systemic toxicity.7 A study on subway particles (which are composed primarily of iron oxide) found these particulates to be toxic. However, magnetite particles on their own did not exhibit toxic effects, showing that the small percentage of other compounds in the dust was the cause of toxicity.8

Interestingly, not only have magnetite nanoparticles been found to be mostly nontoxic, they have also been shown to be beneficial for preventing protein aggregation.9 Based on this study, Fe3O4 nanoparticles could potentially be used as novel therapeutic agents in the treatment of protein aggregation-associated human pathologies.10

In conclusion, many studies have shown that magnetite nanoparticles with a range of surface coatings have low or no toxicity except at very high levels of exposure.


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