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Ex vivo assessment of polyol coated-iron oxide nanoparticles for MRI diagnosis applications: toxicological and MRI contrast enhancement effects |
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| Authors: | Oscar Bomati-Miguel Nuria Miguel-Sancho Ibane Abasolo Ana Paula Candiota Alejandro G. Roca Milena Acosta Simó Schwartz Jr. Carles Arus Clara Marquina Gema Martinez Jesus Santamaria |
| Affiliation: | 1. Departamento de Física Aplicada e Instituto de Ciencia de Materiales Nicolás Cabrera, Facultad de Ciencias, Universidad Autónoma de Madrid, Campus de Cantoblanco, Avda. Francisco Tomás y Valiente 7, 28049, Madrid, Spain 2. Centro de Investigación Biomédica en Red – Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain 3. Instituto de Nanociencia de Aragón (INA), Universidad de Zaragoza, Campus Río Ebro-Edificio I+D, 50018, Zaragoza, Spain 4. Functional Validation and Preclinical Research, CIBBIM-Nanomedicine, Vall d’Hebron Institut de Recerca and Universitat Autònoma de Barcelona, Passeig Vall d’Hebrón 119-129, 08035, Barcelona, Spain 5. Departament de Bioquímica i Biología Molecular, Unitat de Bioquímica de Biociències, Edifici Cs, Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain 6. Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain 7. Drug Delivery and Targeting, CIBBIM-Nanomedicine, Vall d’Hebron Research Institute and Universitat Autònoma de Barcelona, Passeig Vall d’Hebrón 119-129, 08035, Barcelona, Spain 8. Facultad de Ciencias, Instituto de Ciencia de Materiales de Aragón (ICMA, CSIC-Universidad de Zaragoza), C/Pedro Cerbuna 12, 50009, Zaragoza, Spain 9. Departamento de Física de la Materia Condensada, Facultad de Ciencias, Universidad de Zaragoza, C/Pedro Cerbuna 12, 50009, Zaragoza, Spain |
| 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. |
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