title: Efficient penetration of ceric ammonium nitrate oxidant-stabilized gamma-maghemite nanoparticles through the oval and round windows into the rat inner ear as demonstrated by MRI.
abstract: We aimed to evaluate the magnetic resonance imaging (MRI) contrast effect and delivery efficiency through the middle ear into the inner ear using novel super-paramagnetic maghemite (γ-Fe2O3) nanoparticles (NPs) generated using ceric ammonium nitrate (CAN)-mediated oxidation of Fe3O4NPs (CAN-γ-Fe2O3NPs). The CAN-γ-Fe2O3 NPs, having hydrodynamic diameters of 50-60 nm and potentials of +55.2 mV, displayed super-paramagnetic behavior characterized by a saturation magnetization Ms of 75.2 emu/g NPs. The r1 and r2* relaxivity (curve slopes) values were 0.0015 and 189 mmol-1s-1, respectively, indicating strong T2* relaxation maghemite-based NPs. The CAN-γ-Fe2O3NPs were stable in the 7.0 T magnetic field. At 3 h after the tympanic medial wall administration, the NPs had significantly located to the cochlea and vestibule. The signal started to recover at 6 h in the ipsilateral cochlea and by 2 d in the vestibule post-administration. There was no difference in the signal intensity between the left and right ears on the 14th d. Prussian blue staining for iron demonstrated NP distribution in the inner ear tissue. The novel CAN-γ-Fe2O3NPs are a strong MRI T2 contrast agent and penetrated the round and oval windows and have potential application in the molecular imaging of the inner ear. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1883-1891, 2017.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Center for Otolaryngology-Head & Neck Surgery of Chinese PLA, Changhai Hospital, Second Military Medical University, Shanghai, China.|Hearing and Balance Research Unit, Field of Oto-laryngology, School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Jing
authors.initials: J
authors.lastname: Zou
authors.affiliation: Laboratory of Nanoscale Materials and Systems, Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Stella
authors.initials: S
authors.lastname: Ostrovsky
authors.affiliation: Laboratory of Nanoscale Materials and Systems, Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Liron L
authors.initials: LL
authors.lastname: Israel
authors.affiliation: Hearing and Balance Research Unit, Field of Oto-laryngology, School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
authors.affiliation: A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Mikko I
authors.initials: MI
authors.lastname: Kettunen
authors.affiliation: Laboratory of Nanoscale Materials and Systems, Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Jean-Paul Moshe
authors.initials: JM
authors.lastname: Lellouche
authors.affiliation: Hearing and Balance Research Unit, Field of Oto-laryngology, School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Ilmari
authors.initials: I
authors.lastname: Pyykkö
mesh_terms: D000818:Animals; D002563:Cerium / Q000737:chemistry / Q000494:pharmacology; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D007758:Ear, Inner / Q000000981:diagnostic imaging* / Q000378:metabolism; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide; D002563:Cerium; C004653:ceric ammonium nitrate
keywords: biological barrier; functional maghemite nanoparticles; inner ear; magnetic resonance imaging; metal cation doping process for nanoparticle surface engineering