Difference between Toxicities of Iron Oxide Magnetic Nanoparticles with Various Surface-Functional Groups against Human Normal Fibroblasts and Fibrosarcoma Cells

Abstract

Recently, many nanomedical studies have been focused on magnetic nanoparticles (MNPs) because MNPs possess attractive properties for potential uses in imaging, drug delivery, and theranostics. MNPs must have optimized size as well as functionalized surface for such applications. However, careful cytotoxicity and genotoxicity assessments to ensure the biocompatibility and biosafety of MNPs are essential. In this study, Fe3O4 MNPs of different sizes (approximately 10 and 100–150 nm) were prepared with different functional groups, hydroxyl (–OH) and amine (–NH2) groups, by coating their surfaces with tetraethyl orthosilicate (TEOS), 3-aminopropyltrimethoxysilane (APTMS) or TEOS/APTMS. Differential cellular responses to those surface-functionalized MNPs were investigated in normal fibroblasts vs. fibrosarcoma cells. Following the characterization of MNP properties according to size, surface charge and functional groups, cellular responses to MNPs in normal fibroblasts and fibrosarcoma cells were determined by quantifying metabolic activity, membrane integrity, and DNA stability. While all MNPs induced just about 5% or less cytotoxicity and genotoxicity in fibrosarcoma cells at lower than 500 μg/mL, APTMS-coated MNPs resulted in greater than 10% toxicity against normal cells. Particularly, the genotoxicity of MNPs was dependent on their dose, size and surface charge, showing that positively charged (APTMS- or TEOS/APTMS-coated) MNPs induced appreciable DNA aberrations irrespective of cell type. Resultantly, smaller and positively charged (APTMS-coated) MNPs led to more severe toxicity in normal cells than their cancer counterparts. Although it was difficult to fully differentiate cellular responses to various MNPs between normal fibroblasts and their cancer counterparts, normal cells were shown to be more vulnerable to internalized MNPs than cancer cells. Our results suggest that functional groups and sizes of MNPs are critical determinants of degrees of cytotoxicity and genotoxicity, and potential mechanisms of toxicity.

Iron oxide nanoparticles may damage to the neural tissue through iron accumulation, oxidative stress, and protein aggregation

“…Large IONPs are absorbed by endocytosis; but small IONPs incorporated into a cell by pinocytosis [46]. IONPs, after placing in the endosome, are degraded and released iron ions into the cytoplasm [47–49].…”

In vitro toxicity of Fe_mO_n, Fe_mO_n-SiO₂ composite, and SiO₂-Fe_mO_n core-shell magnetic nanoparticles

“…The most commonly used IONP coating materials are silica, 30 polyethylene glycol, 31 dextran and its derivatives, 32 chitosan, 33 and carbon. 34 Very recently, silica-coated IONPs have been tested as contrast agents for biomedical photoacoustic imaging 35 and T1 MRI.…”

Magnetic drug delivery systems

“…The experimental results produced by many researchers have proved this view. Yang et al [38] determined that there was a greater concentration of positively charged (aminopropyltrimethoxysilane (APTMS)-coated) MNPs inside cells than negatively charged (bare or tetraethyl orthosilicate (TEOS)-coated) MNPs. In particular, large numbers of APTMS-coated MNPs widely adhered to the immediate vicinity of the cell membrane, and several particles even translocated to the cell nucleus.…”