title: Si/SiO2 quantum dots cause cytotoxicity in lung cells through redox homeostasis imbalance.
abstract: 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 200 μg/mL for up to 72 h. 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania.
authors.forename: Miruna S
authors.initials: MS
authors.lastname: Stan
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania.
authors.forename: Indira
authors.initials: I
authors.lastname: Memet
authors.affiliation: National Institute for Laser, Plasma and Radiation Physics, 409 Atomistilor, 077125 Bucharest-Magurele, Romania.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Sima
authors.affiliation: National Institute of Materials Physics, 105 bis Atomistilor, 077125 Bucharest-Magurele, Romania.
authors.forename: Traian
authors.initials: T
authors.lastname: Popescu
authors.affiliation: National Institute of Materials Physics, 105 bis Atomistilor, 077125 Bucharest-Magurele, Romania.
authors.forename: Valentin S
authors.initials: VS
authors.lastname: Teodorescu
authors.affiliation: Department of Histology, Faculty of Medicine, Pharmacy and Dentistry, Vasile Goldis Western University of Arad, 86 Rebreanu, 310414 Arad, Romania; Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Rebreanu, 310414 Arad, Romania.
authors.forename: Anca
authors.initials: A
authors.lastname: Hermenean
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania. Electronic address: ancadinischiotu@yahoo.com.
authors.forename: Anca
authors.initials: A
authors.lastname: Dinischiotu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000187:drug effects*; D046529:Microscopy, Electron, Transmission; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D045663:Quantum Dots / Q000737:chemistry*; D017382:Reactive Oxygen Species; D012825:Silicon / Q000633:toxicity*; D012822:Silicon Dioxide / Q000633:toxicity*; D013997:Time Factors
chemical_list: D017382:Reactive Oxygen Species; D012822:Silicon Dioxide; D012825:Silicon
keywords: Oxidative stress; Protein oxidation; Quantum dots; Reduced glutathione; S-glutathionylation