아주대학교

초록/요약

Background: Magnetic nanoparticles (MNPs) have proven themselves to be useful in biomedical research, especially for cell tracking, drug nano-carriers, and bioimaging agents. Previously, the safety and pathological effects of MNPs@SiO2(RITC), a silica coated MNP containing Rhodamine B isothiocyanate (RITC), was evaluated using the MTT assay and chromosome aberration assay. However, these results were insufficient to address the potential dangers of nanoparticles in human cells. Materials and Methods: I investigated gene expression and metabolic changes based on the Affymetrix Human Genome U133 Plus 2.0 Array and metabolic profiling analysis by gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring (SIM) mode (GC-SIM-MS) with HEK 293 cells treated with 0.1 ug/uL and 1.0 ug/uL MNPs@SiO2(RITC). In addition, measurement of the concentration of reactive oxygen species (ROS), transmission electron microscope (TEM) imaging, and ATP analysis were performed to evaluate the effect of MNPs on mitochondrial structure and function. Results and Discussion: Compared to the non-treated control, 22.0% of genes were upregulated and 35.8% were downregulated in 1.0 ug/uL of MNPs@SiO2(RITC) treated cells, whereas 7.8% of genes were upregulated and 1.4% were downregulated in 0.1 ug/uL of MNPs@SiO2(RITC) treated cells, including genes related to molecular transport and cell metabolism. I also found that among amino acids (AAs), glutamic acid was increased by more than 2.0-fold, and expression of 6 genes relative to the glutamic acid metabolic pathway were also disturbed, showing at least 15% down- or 41% upregulation in cells treated with 1.0 ug/uL of MNPs@SiO2(RITC) compared to non-treated control cells. Increases in ROS concentration and mitochondrial damage were observed in 1.0 ug/uL MNPs@SiO2(RITC) treated cells, whereas there were fewer changes in the ROS concentration and less mitochondrial damage in 0.1 ug/uL MNPs@SiO2(RITC) treated cells. In addition, organic acids (OAs) relative to the Kreb’s cycle were also disturbed, and the capacity of ATP synthesis was decreased by more than 42% in 1.0 ug/uL MNPs@SiO2(RITC) treated cells compared to non-treated control cells. However, there were fewer metabolic disturbances, including ATP synthesis, and less altered gene expression in cells treated with 0.1 ug/uL of MNPs@SiO2(RITC) compared to non-treated control cells. Conclusion: These results suggest that overdose (1.0 ug/uL) of MNPs caused transcriptomic and metabolic disturbance, and MNPs should be used at the optimal concentration. In addition, I suggest that a combination of gene expression and metabolic profiles will provide more detailed and sensitive toxicological evaluation for nanoparticles.