Pharmaceutical NanotechnologyLong-term investigation on the phase stability, magnetic behavior, toxicity, and MRI characteristics of superparamagnetic Fe/Fe-oxide core/shell nanoparticles

To efficiently enhance the contrast obtaining from magnetic resonance imaging (MRI), pharmaceutical grade colloidal dispersions of PEG coated iron-based nanoparticles were prepared and compared to conventional pure iron oxide contrast agent. In this study, we synthesized ∼14 nm iron nanoparticles via NaBH4 reduction of iron(III) chloride in an aqueous medium. The resulting nanoparticles were further oxidized by two different methods via (CH3)3NO oxygen transferring agent and exposure to oxygen flow. XRD and electron microscopy analyses confirmed the formation of a second layer on the surface of α-Fe core. As magnetic measurements and Mössbauer spectra of 4-months post prepared nanoparticles showed, 2.3 ± 0.5 nm amorphous oxide shell produced in oxygen flow could not protect the inner metallic iron from oxidation and resulting sample suffered from drastic change in its characteristics. However, (CH3)3NO yielded nanoparticles with 3.6 ± 0.4 and 4.5 ± 0.7 nm crystalline oxide shells that retained their key properties even in long-term examinations. In addition, no significant difference was detected in cytotoxicity results of MTT assay test up to 4-months for core/shell nanoparticles, in comparison with pure iron oxide sample, and all fall below 50% viability in the iron concentration of 400 μg. In vitro MR signal reduction and corresponding relaxometry parameters, especially r2/r1 > 2, assure that all nanoparticles can be administrated for negative contrast enhancement. Accumulation of core/shell nanoparticles in axillary and brachial lymph nodes of examined rats and minimum contrast enhancement of 20% regarding to pure iron oxide implies the efficiency of these materials as potential contrast agent.

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