title: Size-Dependent Translocation Pattern, Chemical and Biological Transformation of Nano- and Submicron-Sized Ferric Oxide Particles in the Central Nervous System.
abstract: The present study investigated the size-dependent translocation pattern and biological fate of intranasally instilled nano- and submicron-sized Fe2O3 particles (40 nm and 280 nm) in the CNS. The particle translocation in different parts of brain at 4 h, 12 h, 24 h, 3 d, 7 d, and 30 d after intranasal instillation were quantified using ICP-MS method. A biexponential model (correlation coefficient r = 0.98-0.99) was satisfactory to describe the particokinetic translocation behavior of Fe2O3 nanoparticles in brain. We found a size-dependent translocation pattern and a time-dependent translocation mode for nano- and submicron-sized Fe2O3 nanoparticles in the olfactory bulb, which are most significant in toxic concerns of nanoparticles in the CNS. The TEM images showed particle-like substances of approximately 35-50 nm were located in the axons of olfactory neurons and in the mitochondria and lysosomes of hippocampus cells in the 40 nm-Fe2O3 exposed mice. The synchrotron-based near-edge X-ray absorption spectroscopy (XANES) was used to identify the chemical forms of the nanoparticles in brain. The XANES results indicate that the presence of chemical speciation of the Fe2O3 nanoparticle (-17%) and protein-complex like apotransferrin-Fe2O3 (-16%) in the olfactory bulb, implying that self-coating of Fe2O3 nanoparticles with transferrin occurred in brain. All the findings suggest size-sensitive manners of nano- and submicron-sized Fe2O3 particles in the brain; the smaller one possesses evident detention properties in the CNS versus the larger one.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Hanqing
authors.initials: H
authors.lastname: Chen
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou
authors.forename: Hailong
authors.initials: H
authors.lastname: Wang
authors.forename: Huiliang
authors.initials: H
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Weiyue
authors.initials: W
authors.lastname: Feng
mesh_terms: D000818:Animals; D001692:Biological Transport; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D005290:Ferric Compounds / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D007700:Kinetics; D008297:Male; D051379:Mice; D008863:Microspheres; D008954:Models, Biological; D053758:Nanoparticles; D009297:Nasal Mucosa / Q000378:metabolism; D010316:Particle Size; D013329:Structure-Activity Relationship
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide