Accumulation and Toxicity of Superparamagnetic Iron Oxide Nanoparticles in Cells and Experimental Animals

Int J Mol Sci. 2016 Aug 19;17(8):1193. doi: 10.3390/ijms17081193.

Abstract

The uptake and distribution of negatively charged superparamagnetic iron oxide (Fe₃O₄) nanoparticles (SPIONs) in mouse embryonic fibroblasts NIH3T3, and magnetic resonance imaging (MRI) signal influenced by SPIONs injected into experimental animals, were visualized and investigated. Cellular uptake and distribution of the SPIONs in NIH3T3 after staining with Prussian Blue were investigated by a bright-field microscope equipped with digital color camera. SPIONs were localized in vesicles, mostly placed near the nucleus. Toxicity of SPION nanoparticles tested with cell viability assay (XTT) was estimated. The viability of NIH3T3 cells remains approximately 95% within 3-24 h of incubation, and only a slight decrease of viability was observed after 48 h of incubation. MRI studies on Wistar rats using a clinical 1.5 T MRI scanner were showing that SPIONs give a negative contrast in the MRI. The dynamic MRI measurements of the SPION clearance from the injection site shows that SPIONs slowly disappear from injection sites and only a low concentration of nanoparticles was completely eliminated within three weeks. No functionalized SPIONs accumulate in cells by endocytic mechanism, none accumulate in the nucleus, and none are toxic at a desirable concentration. Therefore, they could be used as a dual imaging agent: as contrast agents for MRI and for traditional optical biopsy by using Prussian Blue staining.

Keywords: MRI-optical dual imaging; SPIONs; cellular uptake; iron oxide; magnetic nanoparticles; multifunctional cancer diagnostics; optical biopsy of tissues cells.

MeSH terms

  • Animals
  • Contrast Media / metabolism
  • Contrast Media / toxicity
  • Ferric Compounds / metabolism*
  • Ferric Compounds / toxicity*
  • Injections, Intramuscular
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Metal Nanoparticles / toxicity*
  • Mice
  • Microscopy, Atomic Force
  • NIH 3T3 Cells
  • Rats
  • Rats, Wistar

Substances

  • Contrast Media
  • Ferric Compounds
  • ferric oxide