Ex vivo assessment of polyol coated-iron oxide nanoparticles for MRI diagnosis applications: toxicological and MRI contrast enhancement effects

  • Oscar Bomati-Miguel
  • Nuria Miguel-Sancho
  • Ibane Abasolo
  • Ana Paula Candiota
  • Alejandro G. Roca
  • Milena Acosta
  • Simó SchwartzJr.
  • Carles Arus
  • Clara Marquina
  • Gema Martinez
  • Jesus Santamaria
Research Paper

DOI: 10.1007/s11051-014-2292-7

Cite this article as:
Bomati-Miguel, O., Miguel-Sancho, N., Abasolo, I. et al. J Nanopart Res (2014) 16: 2292. doi:10.1007/s11051-014-2292-7
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Abstract

Polyol synthesis is a promising method to obtain directly pharmaceutical grade colloidal dispersion of superparamagnetic iron oxide nanoparticles (SPIONs). Here, we study the biocompatibility and performance as T2-MRI contrast agents (CAs) of high quality magnetic colloidal dispersions (average hydrodynamic aggregate diameter of 16-27 nm) consisting of polyol-synthesized SPIONs (5 nm in mean particle size) coated with triethylene glycol (TEG) chains (TEG-SPIONs), which were subsequently functionalized to carboxyl-terminated meso-2-3-dimercaptosuccinic acid (DMSA) coated-iron oxide nanoparticles (DMSA-SPIONs). Standard MTT assays on HeLa, U87MG, and HepG2 cells revealed that colloidal dispersions of TEG-coated iron oxide nanoparticles did not induce any loss of cell viability after 3 days incubation with dose concentrations below 50 μg Fe/ml. However, after these nanoparticles were functionalized with DMSA molecules, an increase on their cytotoxicity was observed, so that particles bearing free terminal carboxyl groups on their surface were not cytotoxic only at low concentrations (<10 μg Fe/ml). Moreover, cell uptake assays on HeLa and U87MG and hemolysis tests have demonstrated that TEG-SPIONs and DMSA-SPIONs were well internalized by the cells and did not induce any adverse effect on the red blood cells at the tested concentrations. Finally, in vitro relaxivity measurements and post mortem MRI studies in mice indicated that both types of coated-iron oxide nanoparticles produced higher negative T2-MRI contrast enhancement than that measured for a similar commercial T2-MRI CAs consisting in dextran-coated ultra-small iron oxide nanoparticles (Ferumoxtran-10). In conclusion, the above attributes make both types of as synthesized coated-iron oxide nanoparticles, but especially DMSA-SPIONs, promising candidates as T2-MRI CAs for nanoparticle-enhanced MRI diagnosis applications.

Keywords

Polyol-mediated synthesisSuperparamagnetic iron oxide nanoparticlesIn vitro cytotoxicityHemolysis testsContrast agents for nanoparticle-enhanced magnetic resonance imagingNanomedicine

Supplementary material

11051_2014_2292_MOESM1_ESM.doc (9 mb)
Supplementary material 1 (DOC 9166 kb)

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Oscar Bomati-Miguel
    • 1
  • Nuria Miguel-Sancho
    • 2
    • 3
  • Ibane Abasolo
    • 2
    • 4
  • Ana Paula Candiota
    • 2
    • 5
    • 6
  • Alejandro G. Roca
    • 2
    • 3
  • Milena Acosta
    • 2
    • 5
  • Simó SchwartzJr.
    • 2
    • 7
  • Carles Arus
    • 2
    • 5
    • 6
  • Clara Marquina
    • 8
    • 9
  • Gema Martinez
    • 2
    • 3
  • Jesus Santamaria
    • 2
    • 3
  1. 1.Departamento de Física Aplicada e Instituto de Ciencia de Materiales Nicolás Cabrera, Facultad de CienciasUniversidad Autónoma de MadridMadridSpain
  2. 2.Centro de Investigación Biomédica en Red – Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN)ZaragozaSpain
  3. 3.Instituto de Nanociencia de Aragón (INA)Universidad de ZaragozaZaragozaSpain
  4. 4.Functional Validation and Preclinical Research, CIBBIM-NanomedicineVall d’Hebron Institut de Recerca and Universitat Autònoma de BarcelonaBarcelonaSpain
  5. 5.Departament de Bioquímica i Biología Molecular, Unitat de Bioquímica de Biociències, Edifici CsUniversitat Autònoma de BarcelonaCerdanyola del VallèsSpain
  6. 6.Institut de Biotecnologia i de BiomedicinaUniversitat Autònoma de Barcelona08193Spain
  7. 7.Drug Delivery and Targeting, CIBBIM-NanomedicineVall d’Hebron Research Institute and Universitat Autònoma de BarcelonaBarcelonaSpain
  8. 8.Facultad de CienciasInstituto de Ciencia de Materiales de Aragón (ICMA, CSIC-Universidad de Zaragoza)ZaragozaSpain
  9. 9.Departamento de Física de la Materia Condensada, Facultad de CienciasUniversidad de ZaragozaZaragozaSpain