Besides an increased production of inflammatory factors observed in some studies, the addition of iron oxide nanoparticles to macrophages does not exert any major negative impacts.
It was found that the toxicity of SPION can often be reduced considerably choosing a suitable coating polymer that covers the SPION surface. Coating polymers may consist of various different chemical compounds. The toxicity of the SPION is mainly determined by the chemical composition of the respective coatings.

Literature:

1. Muller, K et al. (2007) Biomaterials 28, 1629-1642
2. Haiso, JK et al. (2008) Biomed 21, 820-829
3. Siglienti, I et al. (2006) J Neuroimmunol 173 (2006) 166-173
4. Buyukhatipoglu, K., et al. (2009) J Nanosci Nanotechnol 9(12): p. 6834-43
5. Choi, J.Y., et al.(2010) Bioprocess Biosyst Eng, 2010. 33(1): p. 21-30
6. Hafeli, UO et al., (2009) Mol Pharm, 2009. 6(5): p. 1417-28
7. Mahmoudi, M et al., (2009) J Colloid Interface Sci, 2009. 336(2): p. 510-8

The SPION currently used are made up of two components: A core of iron oxide and a shell of a hygroscopic polymer (Figure below). The shell prevents the nanoparticles from agglomeration, reduces their toxicity, and controls their behaviour and distribution in the body. SPION particles with dextran shells have already been studied intensively and have been admitted for clinical applications by the US Food and Drug Administration (FDA).

^{Source: "Kunzmann et al. 2010, Biochemica & Biophysica Acta, in press"}

Intravenously injected SPION are mainly taken up by macrophages. In these cells, the polymer coating is degraded and is then excreted via the urine or the stool. The iron contained in the SPION is built into the body’s iron stores. The low toxicity of SPION is not surprising considering that natural iron concentrations in the body may be as high as approximately 4000 mg/adult person while no more than 50 – 200 mg/person are administered during medical treatment.
SPION that are provided with a special polymer shell (polyethylene glycol – PEG) are taken up less readily by the macrophages. The retention time of SPION in the body is prolonged through such modification, and the probability of reaching the desired target (for example, the tumor) is increased.

Literature:

1. Muller, K et al., (2007) Biomaterials 28, 1629-1642
2. Kunzmann, A et al., (2010 ) Biochemica et Biophysica Acta, in press,  (doi: 10.1016/j.bbagen.2010.04.007

Environmental engineering uses nanoscale metallic iron to destroy groundwater contaminants ^{[e.g. 1,2]}. Due to their magnetic properties, iron oxide particles (such as magnetite) are very well suited for use as carriers for catalytic substances. Together with their catalytically active coatings, the particles can be applied to clean contaminated groundwater and sewage ^[3]. Much material and time can be saved as compared to conventional methods. It is expected, therefore, that iron-based particles will be increasingly used for sewage treatment and groundwater cleaning, in particular. When used in groundwater, the particles remain in the water-bearing stratum after degradation of the harmful chemicals. They are considered little mobile and are assumed to be remaining where they were applied.

Literature

1. Phenrat T. et al. 2009, Environ Sci Technol 43, 195-200.
2. Phenrat T. et al. 2007, Environ Sci Technol 41, 284–290.
3. Hildebrand H. et al. 2009, Environ Sci Technol 43, 3254–3259.