Characterization of cellular uptake and toxicity of aminosilane-coated iron oxide nanoparticles with different charges in central nervous system-relevant cell culture models

• Published in: International journal of nanomedicine Vol. 8; no. 1; pp. 961 - 970
• Main Authors: Sun, Zhizhi, Yathindranath, Vinith, Worden, Matthew, Thliveris, James A, Chu, Stephanie, Parkinson, Fiona E, Hegmann, Torsten, Miller, Donald W
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2013; Taylor & Francis Ltd; Dove Press; Dove Medical Press
• Subjects: Analysis of Variance; Animals; Astrocytes - drug effects; Astrocytes - metabolism; biocompatibility; brain; Cell Line; Cell Survival - drug effects; cellular accumulation; Central nervous system; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug Carriers - pharmacology; drug delivery; Drug delivery systems; Drugs; Ferric oxide; Health aspects; magnetic field; Magnetic fields; magnetic nanoparticles; Magnetite Nanoparticles - administration & dosage; Magnetite Nanoparticles - chemistry; Mice; Nanoparticles; Nervous system; Neurons; Neurons - drug effects; Neurons - metabolism; Original Research; Physiological aspects; Silanes - chemistry; Silanes - pharmacokinetics; Silanes - pharmacology; Vehicles; Canada; magnetic field; cellular accumulation; drug delivery; brain; magnetic nanoparticles; biocompatibility
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S39048

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.
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.
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.
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.