Exposure of engineered nanoparticles to human lung epithelial cells: influence of chemical composition and catalytic activity on oxidative stress.

The chemical and catalytic activity of nanoparticles has strongly contributed to the current tremendous interest in engineered nanomaterials and often serves as a guiding principle for the design of functional materials. Since it has most recently become evident that such active materials can enter into cells or organisms, the present study investigates the level of intracellular oxidations after exposure to iron-, cobalt-, manganese-, and titania-containing silica nanoparticles and the corresponding pure oxides in vitro. The resulting oxidative stress was quantitatively measured as the release of reactive oxygen species (ROS). The use of thoroughly characterized nanoparticles of the same morphology, comparable size, shape, and degree of agglomeration allowed separation of physical (rate of particle uptake, agglomeration, sedimentation) and chemical effects (oxidations). Three sets of control experiments elucidated the role of nanoparticles as carriers for heavy metal uptake and excluded a potential interference of the biological assay with the nanomaterial. The present results indicate that the particles could efficiently enter the cells by a Trojan-horse type mechanism which provoked an up to eight times higher oxidative stress in the case of cobalt or manganese if compared to reference cultures exposed to aqueous solutions of the same metals. A systematic investigation on iron-containing nanoparticles as used in industrial fine chemical synthesis demonstrated that the presence of catalytic activity could strongly alter the damaging action of a nanomaterial. This indicates that a proactive development of nanomaterials and their risk assessment should consider chemical and catalytic properties of nanomaterials beyond a mere focus on physical properties such as size, shape, and degree of agglomeration.

[1]  K. Jan,et al.  Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. , 2005, Toxicology.

[2]  M. Jacobson Reactive oxygen species and programmed cell death. , 1996, Trends in biochemical sciences.

[3]  Saber M Hussain,et al.  The interaction of manganese nanoparticles with PC-12 cells induces dopamine depletion. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[4]  David Brown,et al.  The pulmonary toxicology of ultrafine particles. , 2002, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.

[5]  I. Salem,et al.  Kinetics and mechanisms of decomposition reaction of hydrogen peroxide in presence of metal complexes , 2000 .

[6]  W. Stark,et al.  Flame-Made Titania/Silica Epoxidation Catalysts: Toward Large-Scale Production , 2002 .

[7]  Robert N Grass,et al.  In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and the effect of particle solubility. , 2006, Environmental science & technology.

[8]  Mark R Wiesner,et al.  Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. , 2006, Nano letters.

[9]  Lutz Mädler,et al.  Controlled synthesis of nanostructured particles by flame spray pyrolysis , 2002 .

[10]  B. Ames,et al.  Detection of picomole levels of hydroperoxides using a fluorescent dichlorofluorescein assay. , 1983, Analytical biochemistry.

[11]  B Chance,et al.  Hydroperoxide metabolism in mammalian organs. , 1979, Physiological reviews.

[12]  J. James,et al.  Research strategies for safety evaluation of nanomaterials, part IV: risk assessment of nanoparticles. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[13]  V. Colvin The potential environmental impact of engineered nanomaterials , 2003, Nature Biotechnology.

[14]  David M. Brown,et al.  The Role of Free Radicals in the Toxic and Inflammatory Effects of Four Different Ultrafine Particle Types , 2003, Inhalation toxicology.

[15]  Peter Gehr,et al.  A three-dimensional cellular model of the human respiratory tract to study the interaction with particles. , 2005, American journal of respiratory cell and molecular biology.

[16]  A. Baiker,et al.  Environmental catalysis on iron oxide-silica aerogels: Selective oxidation of NH3 and reduction of NO by NH3 , 2002 .

[17]  Y. Yoon,et al.  Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[18]  J. Joseph,et al.  Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. , 1999, Free radical biology & medicine.

[19]  J. Jasinski,et al.  Spatially Resolved Energy Electron Loss Spectroscopy Studies of Iron Oxide Nanoparticles , 2006, Microscopy and Microanalysis.

[20]  G. Bartosz,et al.  Light-dependent generation of reactive oxygen species in cell culture media. , 2001, Free radical biology & medicine.

[21]  W R Markesbery,et al.  Oxidative stress hypothesis in Alzheimer's disease. , 1997, Free radical biology & medicine.

[22]  A. Baiker,et al.  Titania-Silica Mixed Oxides: I. Influence of Sol-Gel and Drying Conditions on Structural Properties , 1995 .

[23]  S. Friedlander,et al.  Characteristics of SiO2/TiO2 nanocomposite particles formed in a premixed flat flame , 1998 .

[24]  R. Kumar,et al.  Ferrisilicate Analogs of Zeolites , 1991 .

[25]  David M. Brown,et al.  The role of oxidative stress in the prolonged inhibitory effect of ultrafine carbon black on epithelial cell function. , 1998, Toxicology in vitro : an international journal published in association with BIBRA.

[26]  R. S. Sohal Oxidative stress hypothesis of aging. , 2002, Free radical biology & medicine.

[27]  J. West,et al.  Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[28]  D. Günther,et al.  Analytical evidence of amorphous microdomains within nitridosilicate and nitridoaluminosilicate single crystals , 2005, Analytical and bioanalytical chemistry.

[29]  H. Eagle,et al.  Amino acid metabolism in mammalian cell cultures. , 1959, Science.

[30]  H. Ischiropoulos,et al.  Evaluation of the probe 2',7'-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. , 1992, Chemical research in toxicology.

[31]  B. Halliwell,et al.  Role of free radicals and catalytic metal ions in human disease: an overview. , 1990, Methods in enzymology.

[32]  S. Suib,et al.  Studies of Decomposition of H2O2over Manganese Oxide Octahedral Molecular Sieve Materials , 1998 .

[33]  Y. O’Malley,et al.  Direct oxidation of 2',7'-dichlorodihydrofluorescein by pyocyanin and other redox-active compounds independent of reactive oxygen species production. , 2004, Free radical biology & medicine.

[34]  W. Stark,et al.  Flame synthesis of nanocrystalline ceria-zirconia: effect of carrier liquid. , 2003, Chemical communications.

[35]  R. Sheldon Homogeneous and heterogeneous catalytic oxidations with peroxide reagents , 1993 .

[36]  R. Hutter Titania-silica mixed oxides , 1996 .

[37]  D. Günther,et al.  Inter-laboratory note. Laser ablation inductively coupled plasma mass spectrometric transient signal data acquisition and analyte concentration calculation , 1996 .

[38]  W. Stark,et al.  Titania–silica doped with transition metals via flame synthesis: structural properties and catalytic behavior in epoxidation , 2002 .

[39]  A S KESTON,et al.  THE FLUOROMETRIC ANALYSIS OF ULTRAMICRO QUANTITIES OF HYDROGEN PEROXIDE. , 1965, Analytical biochemistry.

[40]  Robert N Grass,et al.  Oxide nanoparticle uptake in human lung fibroblasts: effects of particle size, agglomeration, and diffusion at low concentrations. , 2005, Environmental science & technology.

[41]  W. Stark,et al.  Glass and Bioglass Nanopowders by Flame Synthesis , 2006 .

[42]  Harald F Krug,et al.  Biological effects of ultrafine model particles in human macrophages and epithelial cells in mono- and co-culture. , 2004, International journal of hygiene and environmental health.

[43]  A. Baiker,et al.  Titania Silica Mixed Oxides: II. Catalytic Behavior in Olefin Epoxidation , 1995 .

[44]  M. Brownlee Biochemistry and molecular cell biology of diabetic complications , 2001, Nature.

[45]  H. Krug,et al.  Formation of reactive oxygen species in rat epithelial cells upon stimulation with fly ash , 2003, Journal of Biosciences.

[46]  A. Baiker,et al.  Synthesis, structural and chemical properties of iron oxide–silica aerogels , 2002 .

[47]  Larry L. Hench,et al.  The potential toxicity of nanomaterials—The role of surfaces , 2006 .

[48]  P. Wardman,et al.  Properties of the radical intermediate obtained on oxidation of 2',7'-dichlorodihydrofluorescein, a probe for oxidative stress. , 2006, Free radical biology & medicine.

[49]  D. Zukor,et al.  Induction of protein oxidation by cobalt and chromium ions in human U937 macrophages. , 2005, Biomaterials.

[50]  H. Krug,et al.  Oops they did it again! Carbon nanotubes hoax scientists in viability assays. , 2006, Nano letters.

[51]  Yoo-Hun Suh,et al.  Porous, Hollow, and Ball‐in‐Ball Metal Oxide Microspheres: Preparation, Endocytosis, and Cytotoxicity , 2006 .

[52]  U. E. Klotz,et al.  Silica-based composite and mixed-oxide nanoparticles from atmospheric pressure flame synthesis , 2006 .

[53]  D. Butterfield Proteomics: a new approach to investigate oxidative stress in Alzheimer's disease brain , 2004, Brain Research.

[54]  G. Bartosz,et al.  2,7‐DICHLOROFLUORESCIN OXIDATION AND REACTIVE OXYGEN SPECIES: WHAT DOES IT MEASURE? , 2000, Cell biology international.

[55]  W. MacNee,et al.  Ultrafine (nanometre) particle mediated lung injury , 1998 .

[56]  Sotiris E. Pratsinis,et al.  Flame Aerosol Synthesis of Vanadia–Titania Nanoparticles: Structural and Catalytic Properties in the Selective Catalytic Reduction of NO by NH3 , 2001 .

[57]  T. Xia,et al.  Toxic Potential of Materials at the Nanolevel , 2006, Science.

[58]  J. West,et al.  Nano-C60 cytotoxicity is due to lipid peroxidation. , 2005, Biomaterials.

[59]  Joseph Loscalzo,et al.  A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds , 1993, Nature.

[60]  J. Scaiano,et al.  Zeolite Encapsulation Decreases TiO2-photosensitized ROS Generation in Cultured Human Skin Fibroblasts† , 2006, Photochemistry and photobiology.

[61]  W. Stark,et al.  Flame synthesis of calcium-, strontium-, barium fluoride nanoparticles and sodium chloride. , 2005, Chemical communications.

[62]  A. Baiker,et al.  Nature of Active Sites in Sol–Gel TiO2–SiO2 Epoxidation Catalysts , 2001 .

[63]  W. Zou,et al.  Cobalt chloride induces PC12 cells apoptosis through reactive oxygen species and accompanied by AP‐1 activation , 2001, Journal of neuroscience research.

[64]  Sotiris E. Pratsinis,et al.  Aerosol flame reactors for manufacture of nanoparticles , 2002 .

[65]  G. Oberdörster,et al.  Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles , 2005, Environmental health perspectives.

[66]  S. Schürch,et al.  Interaction of fine particles and nanoparticles with red blood cells visualized with advanced microscopic techniques. , 2006, Environmental science & technology.

[67]  Wolfgang Kreyling,et al.  Ultrafine Particles Cross Cellular Membranes by Nonphagocytic Mechanisms in Lungs and in Cultured Cells , 2005, Environmental health perspectives.

[68]  R. Brandes,et al.  Analysis of Dichlorodihydrofluorescein and Dihydrocalcein as Probes for the Detection of Intracellular Reactive Oxygen Species , 2004, Free radical research.

[69]  S. Suib,et al.  Studies of oxidative dehydrogenation of ethanol over manganese oxide octahedral molecular sieve catalysts , 1998 .

[70]  M. Seeds,et al.  Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. , 1983, Journal of immunology.

[71]  B. Halliwell,et al.  Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? , 2004, British journal of pharmacology.

[72]  S. Pratsinis,et al.  Design of high-temperature, gas-phase synthesis of hard or soft TiO2 agglomerates , 2006 .

[73]  M. Valko,et al.  Free radicals, metals and antioxidants in oxidative stress-induced cancer. , 2006, Chemico-biological interactions.

[74]  Navid B. Saleh,et al.  Titanium dioxide (P25) produces reactive oxygen species in immortalized brain microglia (BV2): implications for nanoparticle neurotoxicity. , 2006, Environmental science & technology.

[75]  W. Stark,et al.  Fluoro-apatite and calcium phosphate nanoparticles by flame synthesis , 2005 .

[76]  A. Reitzmann,et al.  Direct gas-phase epoxidation of propene with nitrous oxide over modified silica supported FeOx catalysts , 2004 .

[77]  S. Loft,et al.  Cancer risk and oxidative DNA damage in man , 1997, Journal of Molecular Medicine.