Effect of surface coating on the biocompatibility and in vivo MRI detection of iron oxide nanoparticles after intrapulmonary administration

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted special attention as novel nanoprobes capable of improving both the therapy and diagnosis of lung diseases. For safe prospective clinical applications, their biocompatibility has to be assessed after intrapulmonary administration. This study was therefore conducted to understand the biological impact of SPIONs and their further surface-functionalization with polyethylene glycol (PEG) having either negative (i.e. carboxyl) or positive (i.e. amine) terminal in a 1-month longitudinal study following acute and sub-acute exposures. Noninvasive free-breathing MR imaging protocols were first optimized to validate SPIONs detection in the lung and investigate possible subsequent systemic translocation to abdominal organs. Pulmonary Magnetic Resonance Imaging (MRI) allowed successful in vivo detection of SPIONs in the lung using ultra-short echo time sequence. Following high-dose lung administration, MR imaging performed on abdominal organs detected transient accumulation of SPIONs in the liver. Iron quantification using Inductive coupled plasma – Mass mass spectroscopy (ICP-MS) confirmed MRI readouts. Oxidative stress induction and genotoxicity were then conducted to evaluate the biocompatibility of SPIONs with their different formulations in a mouse model. A significant increase in lipid peroxidation was observed in both acute and sub-acute sets and found to regress in a time-dependent manner. PEG functionalized SPIONs revealed a lower effect with no difference between both terminal modifications. Genotoxicity assessments revealed an increase in DNA damage and gene expression of CCL-17 and IL-10 biomarkers following SPIONs administration, which was significantly higher than surface-modified nanoparticles and decreased in a time-dependent manner. However, SPIONs with carboxyl terminal showed a slightly prominent effect compared to amine modification.

• Lung imaging
• MRI
• nanotoxicity
• superparamagnetic iron oxide nanoparticles
• surface charge coating

Acknowledgements

We thank Saud Alotaibi for general help in this work, Dr. Cordula Gruettner from Micromod Partikeltechnologie GmbH for SPION design and characterization and Dr. G. Holzhueter from the University of Rostock for the TEM imaging.

Declaration of interest

This work was supported by National Science Technology and Innovation plan NSTIP strategic technologies programs, project number 12-MED2536, in the Kingdom of Saudi Arabia.

Supplementary material available online

Supplementary Table S1