Silica-coated magnetic nanoparticles induce glucose metabolic dysfunction in vitro via the generation of reactive oxygen species

Abstract

Nanoparticles are a useful material in biomedicine given their unique properties and biocompatibility; however, there is increasing concern regarding the potential toxicity of nanoparticles with respect to cell metabolism. Some evidence suggests that nanoparticles can disrupt glucose and energy homeostasis. In this study, we investigated the metabolomic, transcriptomic, and integrated effects of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@ SiO 2 (RITC)] on glucose metabolism in human embryonic kidney 293 (HEK293) cells. Using gas chromatography-tandem mass spectrometry, we analysed the metabolite profiles of 14 organic acids (OAs), 20 amino acids (AAs), and 13 fatty acids (FAs) after treatment with 0.1 or 1.0 µg/µl MNPs@SiO 2 (RITC) for 12 h. The metabolic changes were highly related to reactive oxygen species (ROS) generation and glucose metabolism. Additionally, effects on the combined metabolome and transcriptome or "metabotranscriptomic network" indicated a relationship between ROS generation and glucose metabolic dysfunction. In the experimental validation, MNPs@SiO 2 (RITC) treatment significantly decreased the amount of glucose in cells and was associated with a reduction in glucose uptake efficiency. Decreased glucose uptake efficiency was also related to ROS generation and impaired glucose metabolism in the metabotranscriptomic network. Our results suggest that exposure to high concentrations of MNPs@SiO 2 (RITC) produces maladaptive alterations in glucose metabolism and specifically glucose uptake as well as related metabolomic and transcriptomic disturbances via increased ROS generation. These findings further indicate that an integrated metabotranscriptomics approach provides useful and sensitive toxicological assessment for nanoparticles.

Silica-Coated Magnetic Nanoparticles Decrease Human Bone Marrow-Derived Mesenchymal Stem Cell Migratory Activity by Reducing Membrane Fluidity and Impairing Focal Adhesion

“…In addition, the viability of human cord blood-derived MSCs was determined to assess the cytotoxic effect of MNPs@SiO 2 (RITC) after 24, 48, and 72 h of treatment with 0–1.0 µg/µL MNPs@SiO 2 (RITC); compared to the control group, no significant cytotoxic effect was observed [48]. Therefore, in this study, hBM-MSCs were treated with 0.1 µg/µL (low dose) MNPs@SiO 2 (RITC)or 1.0 µg/µL (high dose), similarly to previous reports [23,24,47].…”

“…In this study, X-ray diffraction (XRD) analysis using a high-power X-Ray diffractometer (Ultima III, Rigaku, Japan) confirmed the structure of MNPs@SiO 2 (RITC) (data not shown). The silica NPs were composed of identical materials and were of a similar size as the MNPs@SiO 2 (RITC) shell, and their biological effects were similar to those of MNPs@SiO 2 (RITC) [23,24,46,47]. The diameters of the MNPs@SiO 2 (RITC) and silica NPs were 50 nm, and the zeta potential of MNPs@SiO 2 (RITC) was between −40 to −30 mV [4,46].…”

Decrease in Membrane Fluidity and Traction Force Induced by Silica-Coated Magnetic Nanoparticles

“…Thus, for evaluating network-based analysis, we used a combination of transcriptome and metabolome networks, termed the metabotranscriptomic network, through the substitution of amino acid and organic acid pro les (cut-off ± 20% change), as described in our previous report [17]. In the group treated with 1.0 µg/µl MNPs@SiO 2 (RITC), amino acid, organic acid, and free fatty acid pro les showed increased levels of tyrosine, pyruvic acid, glutamic acid, lysine and lignoceric acid; in contrast, decreased levels of cysteine, asparagine, 3-hydroxybutyric acid, glutamine, serine, aspartic acid, oxaloacetic acid, glycine, and acetoacetic acid were observed [37]. The combined network provided more reliable information than the transcriptomic network alone, with more pronounced changes also being detected in 1.0 µg/µl than in 0.1 µg/µl MNPs@SiO 2 (RITC)-treated cells and control cells ( Fig.…”

Metabolome Changes in Cerebral Ischemia

“…Metabolic profiling reflects the phenotype of biological changes in cellular mechanisms [37][38][39]. A metabolic profile can be analyzed with samples from various sources, including biological fluids, cells, tissues, and whole organisms (e.g., plants and microorganisms) [37].…”