Abstract
Cerium oxide nanoparticles, nanoceria, have been proposed as drug delivery devices and therapeutic tools also for neurological diseases due to their antioxidant properties and neuroprotective effects. However, very little evidence has been hitherto obtained on the passage of nanoceria across the blood-brain barrier in vivo. Distribution of in-house synthesized 10 nm nanoceria in spleen, liver, lung, kidney and brain was here examined at 24 h after a single iv injection of a nanoceria suspension at two concentrations (1 or 20 mg/kg). The use of fluorescein isothiocyanate-conjugated nanoceria allowed their visualization in confocal microscopy. The investigation was also pursued with inductively coupled plasma-mass spectrometry and with transmission and scanning electron microscopy. Consistently with previous investigations, these approaches pointed to accumulation of the largest amount of nanoceria in the liver and spleen, with deposition also in the kidney and lung, and no signs of overt pathology of these tissues. In the brain, confocal microscopy revealed penetration of fluorescent nanoceria into the parenchyma, albeit in limited amount, and astrocytic activation. Occurrence of electron-dense nanoceria-like particles in the cerebral cortex, sparse or in agglomerates, was confirmed by the ultrastructural study. The present findings contribute novel knowledge by showing nanoceria entry into the brain parenchyma.