title: Silicon-based quantum dots induce inflammation in human lung cells and disrupt extracellular matrix homeostasis.
abstract: Quantum dots (QDs) are nanocrystalline semiconductor materials that have been tested for biological applications such as cancer therapy, cellular imaging and drug delivery, despite the serious lack of information of their effects on mammalian cells. The present study aimed to evaluate the potential of Si/SiO2 QDs to induce an inflammatory response in MRC-5 human lung fibroblasts. Cells were exposed to different concentrations of Si/SiO2 QDs (25-200 μg·mL(-1)) for 24, 48, 72 and 96 h. The results obtained showed that uptake of QDs was dependent on biocorona formation and the stability of nanoparticles in various biological media (minimum essential medium without or with 10% fetal bovine serum). The cell membrane damage indicated by the increase in lactate dehydrogenase release after exposure to QDs was dose- and time-dependent. The level of lysosomes increased proportionally with the concentration of QDs, whereas an accumulation of autophagosomes was also observed. Cellular morphology was affected, as shown by the disruption of actin filaments. The enhanced release of nitric oxide and the increase in interleukin-6 and interleukin-8 protein expression suggested that nanoparticles triggered an inflammatory response in MRC-5 cells. QDs decreased the protein expression and enzymatic activity of matrix metalloproteinase (MMP)-2 and MMP-9 and also MMP-1 caseinase activity, whereas the protein levels of MMP-1 and tissue inhibitor of metalloproteinase-1 increased. The present study reveals for the first time that silicon-based QDs are able to generate inflammation in lung cells and cause an imbalance in extracellular matrix turnover through a differential regulation of MMPs and tissue inhibitor of metalloproteinase-1 protein expression.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, Romania.
authors.forename: Miruna-Silvia
authors.initials: MS
authors.lastname: Stan
authors.affiliation: National Institute for Laser, Plasma and Radiation Physics, Bucharest-Magurele, Romania.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Sima
authors.affiliation: Faculty of Chemistry, University of Bucharest, Romania.
authors.forename: Ludmila Otilia
authors.initials: LO
authors.lastname: Cinteza
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, Romania.
authors.forename: Anca
authors.initials: A
authors.lastname: Dinischiotu
mesh_terms: D001343:Autophagy; D005109:Extracellular Matrix / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008247:Lysosomes / Q000378:metabolism; D045663:Quantum Dots; D012825:Silicon / Q000737:chemistry*
chemical_list: D012825:Silicon
keywords: autophagy; cytokines; inflammation; matrix metalloproteinases; quantum dots