Si/SiO2 quantum dots cause cytotoxicity in lung cells through redox homeostasis imbalance

• Published in: Chemico-biological interactions 2014-09, Vol.220, p.102-115
• Main Authors: Stan, Miruna S., Memet, Indira, Sima, Cornelia, Popescu, Traian, Teodorescu, Valentin S., Hermenean, Anca, Dinischiotu, Anca
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Cell Survival - drug effects; Fibroblasts - drug effects; Homeostasis - drug effects; Humans; Lung - drug effects; Microscopy, Electron, Transmission; Oxidation-Reduction; Oxidative stress; Oxidative Stress - drug effects; Protein oxidation; Quantum dots; Quantum Dots - chemistry; Reactive Oxygen Species; Reduced glutathione; S-glutathionylation; Silicon - toxicity; Silicon Dioxide - toxicity; Time Factors
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2014.06.020

•Effects of Si/SiO2 QDs on cell redox homeostasis in MRC-5 cells were investigated.•Exposure to QDs led to a time-dependent decrease in cell viability and biomass.•Si/SiO2 QDs had a significant impact on intracellular distribution of glutathione.•Si/SiO2 QDs induced protein oxidation and actin S-glutathionylation. Si/SiO2 quantum dots (QDs) are novel particles with unique physicochemical properties that promote them as potential candidates for biomedical applications. Although their interaction with human cells has been poorly investigated, oxidative stress appears to be the main factor involved in the cytotoxicity of these nanoparticles. In this study, we show for the first time the influence of Si/SiO2 QDs on cellular redox homeostasis and glutathione distribution in human lung fibroblasts. The nanoparticles morphology, composition and structure have been investigated using high resolution transmission electron microscopy (HRTEM), selected area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD) analysis. MRC-5 cells (human lung fibroblasts) were incubated with various concentrations of Si/SiO2 QDs ranging between 25 and 200μg/mL for up to 72h. The results of the MTT and sulforhodamine B assays showed that exposure to QDs led to a time-dependent decrease in cell viability and biomass. The increase in reactive oxygen species (ROS) and malondialdehyde (MDA) levels together with the lower glutathione content suggested that the cellular redox homeostasis was altered. Regarding GSH distribution, the first two days of treatment resulted in a localization of GSH mainly in the cytoplasm, while at longer incubation time the nuclear/cytoplasmic ratio indicated a nuclear localization. These modifications of cell redox state also affected the redox status of proteins, which was demonstrated by the accumulation of oxidized proteins and actin S-glutathionylation. In addition, the externalization of phosphatidylserine provided evidence that apoptosis might be responsible for cell death, but necrosis was also revealed. Our results suggest that Si/SiO2 quantum dots exerted cytotoxicity on MRC-5 cells by disturbing cellular homeostasis which had an effect upon protein redox status.