title: Ultrasmall cationic superparamagnetic iron oxide nanoparticles as nontoxic and efficient MRI contrast agent and magnetic-targeting tool.
abstract: Fully dispersible, cationic ultrasmall (7 nm diameter) superparamagnetic iron oxide nanoparticles, exhibiting high relaxivity (178 mM(-1)s(-1) in 0.47 T) and no acute or subchronic toxicity in Wistar rats, were studied and their suitability as contrast agents for magnetic resonance imaging and material for development of new diagnostic and treatment tools demonstrated. After intravenous injection (10 mg/kg body weight), they circulated throughout the vascular system causing no microhemorrhage or thrombus, neither inflammatory processes at the mesentery vascular bed and hepatic sinusoids (leukocyte rolling, adhesion, or migration as evaluated by intravital microscopy), but having been spontaneously concentrated in the liver, spleen, and kidneys, they caused strong negative contrast. The nanoparticles are cleared from kidneys and bladder in few days, whereas the complete elimination from liver and spleen occurred only after 4 weeks. Ex vivo studies demonstrated that cationic ultrasmall superparamagnetic iron oxide nanoparticles caused no effects on hepatic and renal enzymes dosage as well as on leukocyte count. In addition, they were readily concentrated in rat thigh by a magnet showing its potential as magnetically targeted carriers of therapeutic and diagnostic agents. Summarizing, cationic ultrasmall superparamagnetic iron oxide nanoparticles are nontoxic and efficient magnetic resonance imaging contrast agents useful as platform for the development of new materials for application in theranostics.
authors.affiliation: Laboratory of Supramolecular Chemistry and Nanotechnology, Department of Fundamental Chemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Mayara Klimuk
authors.initials: MK
authors.lastname: Uchiyama
authors.affiliation: Laboratory of Supramolecular Chemistry and Nanotechnology, Department of Fundamental Chemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Sergio Hiroshi
authors.initials: SH
authors.lastname: Toma
authors.affiliation: Laboratory of Experimental Toxicology, Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Stephen Fernandes de Paula
authors.initials: SF
authors.lastname: Rodrigues
authors.affiliation: Laboratory of Experimental Toxicology, Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Ana Lucia Borges
authors.initials: AL
authors.lastname: Shimada
authors.affiliation: Laboratory of Experimental Toxicology, Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Rodrigo Azevedo
authors.initials: RA
authors.lastname: Loiola
authors.affiliation: Magnetic Resonance Laboratory, Department of General Physics, Institute of Physics, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Hernán Joel
authors.initials: HJ
authors.lastname: Cervantes Rodríguez
authors.affiliation: Analysis and Research Group in Spectrometry, Department of Fundamental Chemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Pedro Vitoriano
authors.initials: PV
authors.lastname: Oliveira
authors.affiliation: Analysis and Research Group in Spectrometry, Department of Fundamental Chemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Maciel Santos
authors.initials: MS
authors.lastname: Luz
authors.affiliation: Magnetic Resonance Laboratory, Department of General Physics, Institute of Physics, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Said Rahnamaye
authors.initials: SR
authors.lastname: Rabbani
authors.affiliation: Laboratory of Supramolecular Chemistry and Nanotechnology, Department of Fundamental Chemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Henrique Eisi
authors.initials: HE
authors.lastname: Toma
authors.affiliation: Laboratory of Experimental Toxicology, Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Sandra Helena
authors.initials: SH
authors.lastname: Poliselli Farsky
authors.affiliation: Laboratory of Supramolecular Chemistry and Nanotechnology, Department of Fundamental Chemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Koiti
authors.initials: K
authors.lastname: Araki
mesh_terms: D000818:Animals; D002412:Cations; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000633:toxicity; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D002412:Cations; D003287:Contrast Media; D058185:Magnetite Nanoparticles
keywords: MRI; cationic USPIOs; contrast agent; in vivo toxicity; intra-vital microscopy; magnetic targeting