title: Characterization of cellular uptake and toxicity of aminosilane-coated iron oxide nanoparticles with different charges in central nervous system-relevant cell culture models.
abstract: BACKGROUND
  Aminosilane-coated iron oxide nanoparticles (AmS-IONPs) have been widely used in constructing complex and multifunctional drug delivery systems. However, the biocompatibility and uptake characteristics of AmS-IONPs in central nervous system (CNS)-relevant cells are unknown. The purpose of this study was to determine the effect of surface charge and magnetic field on toxicity and uptake of AmS-IONPs in CNS-relevant cell types.
  
  
  METHODS
  The toxicity and uptake profile of positively charged AmS-IONPs and negatively charged COOH-AmS-IONPs of similar size were examined using a mouse brain microvessel endothelial cell line (bEnd.3) and primary cultured mouse astrocytes and neurons. Cell accumulation of IONPs was examined using the ferrozine assay, and cytotoxicity was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
  
  
  RESULTS
  No toxicity was observed in bEnd.3 cells at concentrations up to 200 μg/mL for either AmS-IONPs or COOH-AmS-IONPs. AmS-IONPs at concentrations above 200 μg/mL reduced neuron viability by 50% in the presence or absence of a magnetic field, while only 20% reductions in viability were observed with COOH-AmS-IONPs. Similar concentrations of AmS-IONPs in astrocyte cultures reduced viability to 75% but only in the presence of a magnetic field, while exposure to COOH-AmS-IONPs reduced viability to 65% and 35% in the absence and presence of a magnetic field, respectively. Cellular accumulation of AmS-IONPs was greater in all cell types examined compared to COOH-AmS-IONPs. Rank order of cellular uptake for AmS-IONPs was astrocytes > bEnd.3 > neurons. Accumulation of COOH-AmS-IONPs was minimal and similar in magnitude in different cell types. Magnetic field exposure enhanced cellular accumulation of both AmS- and COOH-AmS-IONPs.
  
  
  CONCLUSIONS
  Both IONP compositions were nontoxic at concentrations below 100 μg/mL in all cell types examined. At doses above 100 μg/mL, neurons were more sensitive to AmS-IONPs, whereas astrocytes were more vulnerable toward COOH-AmS-IONPs. Toxicity appears to be dependent on the surface coating as opposed to the amount of iron-oxide present in the cell.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Zhizhi
authors.initials: Z
authors.lastname: Sun
authors.forename: Vinith
authors.initials: V
authors.lastname: Yathindranath
authors.forename: Matthew
authors.initials: M
authors.lastname: Worden
authors.forename: James A
authors.initials: JA
authors.lastname: Thliveris
authors.forename: Stephanie
authors.initials: S
authors.lastname: Chu
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Parkinson
authors.forename: Torsten
authors.initials: T
authors.lastname: Hegmann
authors.forename: Donald W
authors.initials: DW
authors.lastname: Miller
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012821:Silanes / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D012821:Silanes
keywords: biocompatibility; brain; cellular accumulation; drug delivery; magnetic field; magnetic nanoparticles