title: Acute Toxicity Evaluation of Glycosylated Gd3+-Based Silica Nanoprobe.
abstract: Early stage diseases diagnosed using magnetic resonance imaging (MRI) techniques is of high global interest as a potent noninvasive modality. MRI contrast agents are improved through modifications in structural and physicochemical properties of the applied nanoprobes. But, the potential toxic effects of nanoprobes upon exposure to biological systems are still a major concern.
  
  
  
  In this study, the acute toxicity of glycosylated Gd3+-based silica mesoporous nanospheres (GSNs) as a MRI contrast agent was evaluated in Balb/c mice. In order to evaluate in vivo toxicity of GSN, preclinical studies, daily weight monitoring, hematological/blood chemistry tests, and histological assessment were conducted. Magnetic resonance relaxivities of GSN was determined using a MRI scanner.
  
  
  
  The obtained results suggest that in vivo toxicity of GSN was mostly influenced by nanoparticle surface area, functionality, and nanoparticle zeta potential. The maximum tolerated dose (MTD) increased in the following order: mesoporous silica nanospheres (MSNs) at 1 mg/mice < GSN (aspect ratio 1, 2, 8) at 40 mg/mice. The results also indicate GSN, one of the best cell imaging contrast agent, which does not show any significant toxicity on multiple vital organs following injection of 20 mg/mice, while a significant T1-weighted enhancement was observed in whole body of a Balb/c mice 15 min postinjection of (5 μmol/kg) of body weight of GSN.
  
  
  
  These results shed light on the functionality of MSNs to minimize in vivo toxicity. Also, glyconanoprobe can be beneficially used for nanomedicine and cellular imaging applications without any significant toxicity.
authors.affiliation: Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran. mehravi.b@iums.ac.ir.|Nanofanavri Kian Gostar Company, Roshd Center, Iran University of Medical Sciences, Tehran, Iran. mehravi.b@iums.ac.ir.|Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. mehravi.b@iums.ac.ir.|Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran. mehravi.b@iums.ac.ir.
authors.forename: Bita
authors.initials: B
authors.lastname: Mehravi
authors.affiliation: Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ali Mohammad
authors.initials: AM
authors.lastname: Alizadeh
authors.affiliation: Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Khodayari
authors.affiliation: Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Khodayari
authors.affiliation: Nanofanavri Kian Gostar Company, Roshd Center, Iran University of Medical Sciences, Tehran, Iran.|Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Khadijeh
authors.initials: K
authors.lastname: Ashtari
authors.affiliation: Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mojdeh
authors.initials: M
authors.lastname: Mohseni
authors.affiliation: Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Neda Iranpour
authors.initials: NI
authors.lastname: Anaraki
authors.affiliation: Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Elham Afjeh
authors.initials: EA
authors.lastname: Dana
authors.affiliation: Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Safari
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran. amanlou@tums.ac.ir.
authors.forename: Massoud
authors.initials: M
authors.lastname: Amanlou
mesh_terms: D000818:Animals; D005682:Gadolinium / Q000633:toxicity*; D006031:Glycosylation; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D020714:Maximum Tolerated Dose; D008807:Mice, Inbred BALB C; D054118:Nanospheres / Q000633:toxicity*; D016062:Porosity; D012822:Silicon Dioxide / Q000633:toxicity*; D023382:Toxicity Tests, Acute
chemical_list: D012822:Silicon Dioxide; D005682:Gadolinium
keywords: Contrast agents; MRI; Mesoporous silica nanospheres; Toxicity