Biomedical applications of magnetic nanoparticles (MNP), including superparamagnetic nanoparticles, have expanded dramatically in recent years. Systematic and standardized @entity137 assessment to ensure the biosafety and biocompatibility of those applications is compulsory. We investigated whether exposure to @entity2194 ( @entity2194 ) from e.g. magnetic resonance imaging (MRI) could affect the @entity137 of superparamagnetic @entity1933 (SPIO) nanoparticles using @entity19 hepatocytes and @entity11830 , a liver-selective MRI contrast agent as a model system. We show that while the SPIO satisfied the conventional @entity137 assessment, clinical doses combined with @entity2194 exposure exerts synergistic adverse effects such as reduced cell viability, apoptosis, and cell cycle aberrations on hepatocytes in  vitro and in  vivo. Concomitant treatments with the SPIO and @entity2194 generated SPIO aggregates, which demonstrated enhanced cellular uptake, was sufficient to induce the @entity137 without further @entity2194 , emphasizing that the SPIO aggregates were the predominant source of the @entity137 . Interestingly, the apoptotic effect was dependent on levels of reactive @entity26 species (ROS) and SPIO uptake while the reduced cell viability was independent of these factors. Moreover, long-term monitoring showed a significant increase in multinuclear giant cells in the cells concomitantly treated with the SPIO and @entity2194 compared with the control. The results demonstrate that the SPIO produces unidentified @entity137 on liver in the presence of @entity2194 and the SPIO aggregates predominantly exert the effect. Since aggregation of MNP in biological milieu in the presence of strong @entity2194 is inevitable, a fundamentally different approach to surface fabrication is essential to increase the biocompatibility of MNP.

The effect of static magnetic fields on the aggregation and XXXX of magnetic nanoparticles.

@entity2194 :: ('MESH:D005128', 'Disease') :: ['static magnetic field', 'SMF'] @entity137 :: ('MESH:D064420', 'Disease') :: ['cytotoxicity'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity1933 :: ('MESH:C000499', 'Chemical') :: ['iron oxide'] @entity11830 :: ('MESH:C065507', 'Chemical') :: ['ferucarbotran']
@entity137 :: (MESH:D064420,Disease) :: ['cytotoxicity']
