Abstract
Studies on the health effects of air-pollution particles suggest that injury may result from inhalation of airborne ultrafine particles (<100 nm in diameter). Engineered nanomaterials (<100 nm in at least one dimension) may also be harmful if inhaled. Nanomaterials deposited on the respiratory epithelial tract are thought to cross the air-blood barrier, especially via the expansive alveolar region, into the systemic circulation to reach end organs (e.g., myocardium, liver, pancreas, kidney, and spleen). Since ambient ultrafine particles are difficult to track, studies of defined engineered nanomaterials have been used to obtain valuable information on how nanomaterials interact with and traffic across the air-blood barrier of mammalian lungs. Since specific mechanistic information on how nanomaterials interact with the lung is difficult to obtain using in vivo or ex vivo lungs due to their complex anatomy, in vitro alveolar epithelial models have been of considerable value in determining nanomaterial-lung interactions. In this review, we provide information on mechanisms underlying lung alveolar epithelial injury caused by various nanomaterials and on nanomaterial trafficking across alveolar epithelium that may lead to end-organ injury.
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Adson A, Raub TJ, Burton PS et al (1994) Quantitative approaches to delineate paracellular diffusion in cultured epithelial cell monolayers. J Pharm Sci 83:1529–1536
Anglin EJ, Cheng L, Freeman WR et al (2008) Porous silicon in drug delivery devices and materials. Adv Drug Deliv Rev 60:1266–1277
Baker GL, Gupta A, Clark ML et al (2008) Inhalation toxicity and lung toxicokinetics of C60 fullerene nanoparticles and microparticles. Toxicol Sci 101:122–131
Bakry R, Vallant RM, Najam-ul-Haq M et al (2007) Medicinal applications of fullerenes. Int J Nanomedicine 2:639–649
Bakshi MS, Zhao L, Smith R et al (2008) Metal nanoparticle pollutants interfere with pulmonary surfactant function in vitro. Biophys J 94:855–868
Beckett WS, Chalupa DF, Pauly-Brown A et al (2005) Comparing inhaled ultrafine versus fine zinc oxide particles in healthy adults: a human inhalation study. Am J Respir Crit Care Med 171:1129–1135
Berry JP, Arnoux B, Stanislas G et al (1977) A microanalytic study of particles transport across the alveoli: role of blood platelets. Biomedicine 27:354–357
Borm P, Klaessig FC, Landry TD et al (2006a) Research strategies for safety evaluation of nanomaterials, part V: role of dissolution in biological fate and effects of nanoscale particles. Toxicol Sci 90:23–32
Borm PJ, Robbins D, Haubold S et al (2006b) The potential risks of nanomaterials: a review carried out for ECETOC. Part Fibre Toxicol 3:11
Bosi S, Feruglio L, Da Ros T et al (2004) Hemolytic effects of water-soluble fullerene derivatives. J Med Chem 47:6711–6715
Bottini M, D’Annibale F, Magrini A et al (2007) Quantum dot-doped silica nanoparticles as probes for targeting of T-lymphocytes. Int J Nanomedicine 2:227–233
Brown JS, Zeman KL, Bennett WD (2002) Ultrafine particle deposition and clearance in the healthy and obstructed lung. Am J Respir Crit Care Med 166:1240–1247
Brunner TJ, Wick P, Manser P et al (2006) In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and the effect of particle solubility. Environ Sci Technol 40:4374–4381
Camps X, Hirsch A (1997) Efficient cyclopropanation of C60 from malonates. JCS Perkin Trans 1:1595–1596
Card JW, Zeldin DC, Bonner JC et al (2008) Pulmonary applications and toxicity of engineered nanoparticles. Am J Physiol Lung Cell Mol Physiol 295:L400–L411
Cheek JM, Evans MJ, Crandall ED (1989a) Type I cell-like morphology in tight alveolar epithelial monolayers. Exp Cell Res 184:375–387
Cheek JM, Kim KJ, Crandall ED (1989b) Tight monolayers of rat alveolar epithelial cells: bioelectric properties and active sodium transport. Am J Physiol 256:C688–C693
Cho SJ, Maysinger D, Jain M et al (2007) Long-term exposure to CdTe quantum dots causes functional impairments in live cells. Langmuir 23:1974–1980
Choi HS, Liu W, Misra P et al (2007) Renal clearance of quantum dots. Nat Biotechnol 25:1165–1170
Cohen MS, Stern JM, Vanni AJ et al (2007) In vitro analysis of a nanocrystalline silver-coated surgical mesh. Surg Infect (Larchmt) 8:397–403
Conner SD, Schmid SL (2003) Regulated portals of entry into the cell. Nature 422:37–44
Deguchi S, Yamazaki T, Mukai SA et al (2007) Stabilization of C60 nanoparticles by protein adsorption and its implications for toxicity studies. Chem Res Toxicol 20:854–858
Derfus AM, Chan WCW, Bhatia SN (2004) Intracellular delivery of quantum dots for live cell labeling and organelle tracking. Adv Materials 16:961–969
Dick CA, Brown DM, Donaldson K et al (2003) The role of free radicals in the toxic and inflammatory effects of four different ultrafine particle types. Inhal Toxicol 15:39–52
Doherty GJ, McMahon HT (2009) Mechanisms of endocytosis. Annu Rev Biochem 78:857–902
Donaldson K, Tran L, Jimenez LA et al (2005) Combustion-derived nanoparticles: a review of their toxicology following inhalation exposure. Part Fibre Toxicol 2:10
Donaldson K, Aitken R, Tran L et al (2006) Carbon nanotubes: a review of their properties in relation to pulmonary toxicology and workplace safety. Toxicol Sci 92:5–22
Eichmann SL, Anekal SG, Bevan MA (2008) Electrostatically confined nanoparticle interactions and dynamics. Langmuir 24:714–721
Erogbogbo F, Yong KT, Roy I et al (2008) Biocompatible luminescent silicon quantum dots for imaging of cancer cells. ACS Nano 2:873–878
Evans SA, Al-Mosawi A, Adams RA et al (2006) Inflammation, edema, and peripheral blood changes in lung-compromised rats after instillation with combustion-derived and manufactured nanoparticles. Exp Lung Res 32:363–378
Ferin J, Oberdorster G, Penney DP (1992) Pulmonary retention of ultrafine and fine particles in rats. Am J Respir Cell Mol Biol 6:535–542
Frampton MW (2001) Systemic and cardiovascular effects of airway injury and inflammation: ultrafine particle exposure in humans. Environ Health Perspect 109(Suppl 4):529–532
Frampton MW, Utell MJ, Zareba W et al. (2004) Effects of exposure to ultrafine carbon particles in healthy subjects and subjects with asthma. Res Rep Health Eff Inst (126):1–47; discussion 49–63
Franklin NM, Rogers NJ, Apte SC et al (2007) Comparative toxicity of nanoparticulate ZnO, bulk ZnO, and ZnCl2 to a freshwater microalga (Pseudokirchneriella subcapitata): the importance of particle solubility. Environ Sci Technol 41:8484–8490
Furuyama A, Kanno S, Kobayashi T et al (2009) Extrapulmonary translocation of intratracheally instilled fine and ultrafine particles via direct and alveolar macrophage-associated routes. Arch Toxicol 83:429–437
Geiser M, Kreyling WG (2010) Deposition and biokinetics of inhaled nanoparticles. Part Fibre Toxicol 7:2
Geiser M, Rothen-Rutishauser B, Kapp N et al (2005) Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells. Environ Health Perspect 113:1555–1560
Geiser M, Casaulta M, Kupferschmid B et al (2008) The role of macrophages in the clearance of inhaled ultrafine titanium dioxide particles. Am J Respir Cell Mol Biol 38:371–376
Geys J, Nemmar A, Verbeken E et al (2008) Acute toxicity and prothrombotic effects of quantum dots: impact of surface charge. Environ Health Perspect 116:1607–1613
Gharbi N, Pressac M, Hadchouel M et al (2005) C60 fullerene is a powerful antioxidant in vivo with no acute or subacute toxicity. Nano Lett 5:2578–2585
Gojova A, Guo B, Kota RS et al (2007) Induction of inflammation in vascular endothelial cells by metal oxide nanoparticles: effect of particle composition. Environ Health Perspect 115:403–409
Gold DR, Litonjua A, Schwartz J et al (2000) Ambient pollution and heart rate variability. Circulation 101:1267–1273
Goldberg MS, Bailar JC III, Burnett RT et al (2000) Identifying subgroups of the general population that may be susceptible to short-term increases in particulate air pollution: a time-series study in Montreal, Quebec. Res Rep Health Eff Inst 97:7–113, discussion 115–120
Goodman CM, McCusker CD, Yilmaz T et al (2004) Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. Bioconjug Chem 15:897–900
Gurr JR, Wang AS, Chen CH et al (2005) Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. Toxicology 213:66–73
Hamoir J, Nemmar A, Halloy D et al (2003) Effect of polystyrene particles on lung microvascular permeability in isolated perfused rabbit lungs: role of size and surface properties. Toxicol Appl Pharmacol 190:278–285
Hardman R (2006) A toxicologic review of quantum dots: toxicity depends on physicochemical and environmental factors. Environ Health Perspect 114:165–172
Heckel K, Kiefmann R, Dorger M et al (2004) Colloidal gold particles as a new in vivo marker of early acute lung injury. Am J Physiol Lung Cell Mol Physiol 287:L867–L878
Hefland RB, Schwarzel PE, Johansen BV et al (2001) Silica-induced cytokine release from A549 cells: importance of surface area versus size. Hum Exp Toxicol 20:46–55
Helland A, Wick P, Koehler A et al (2007) Reviewing the environmental and human health knowledge base of carbon nanotubes. Environ Health Perspect 115:1125–1131
Helland A, Wick P, Koehler A et al (2008) Reviewing the environmental and human health knowledge base of carbon nanotubes. Ciên Saúde Colet 13:441–452
Henneberger A, Zareba W, Ibald-Mulli A et al (2005) Repolarization changes induced by air pollution in ischemic heart disease patients. Environ Health Perspect 113:440–446
Hoet PH, Nemmar A, Nemery B (2004) Health impact of nanomaterials? Nat Biotechnol 22:19
Hong S, Bielinska AU, Mecke A et al (2004) Interaction of poly(amidoamine) dendrimers with supported lipid bilayers and cells: hole formation and the relation to transport. Bioconjug Chem 15:774–782
Hong S, Hessler JA, Banaszak Holl MM et al (2006a) Physical interactions of nanoparticles with biological membranes: the observation of nanoscale hole formation. Chem Health Saf 13:16–20
Hong S, Leroueil PR, Jnaus EK et al (2006b) Interaction of polycationic polymers with supported lipid bilayers and cells: nanoscale hole formation and enhanced membrane permeability. Bioconjugate Chem 17:728–734
Hurt RH, Monthioux M, Kane A (2006) Toxicology of carbon nanomaterials: status, trends, and perspectives on the special issue. Carbon 44:1028–1033
Hussain SM, Hess KL, Gearhart JM et al (2005) In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol In Vitro 19:975–983
Isakovic A, Markovic Z, Todorovic-Markovic B et al (2006) Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene. Toxicol Sci 91:173–183
Jacobsen NR, Moller P, Jensen KA et al (2009) Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice. Part Fibre Toxicol 6:2
Jeng HA, Swanson J (2006) Toxicity of metal oxide nanoparticles in mammalian cells. J Environ Sci Health A Tox Hazard Subst Environ Eng 41:2699–2711
Jia G, Wang H, Yan L et al (2005) Cytotoxicity of carbon nanomaterials: single-wall nanotube, multi-wall nanotube, and fullerene. Environ Sci Technol 39:1378–1383
Kam NWS, Jessop TC, Wender PA et al (2004) Nanotube molecular transporters: internalization of carbon nano-tube-protein conjugates into mammalian cells. J Am Chem Soc 126:6850–6851
Karabanovas V, Zakarevicius E, Sukackaite A et al (2008) Examination of the stability of hydrophobic (CdSe)ZnS quantum dots in the digestive tract of rats. Photochem Photobiol Sci 7:725–729
Karlsson HL, Nygren J, Moller L (2004) Genotoxicity of airborne particulate matter: the role of cell-particle interaction and of substances with adduct-forming and oxidizing capacity. Mutat Res 565:1–10
Karlsson HL, Nilsson L, Moller L (2005) Subway particles are more genotoxic than street particles and induce oxidative stress in cultured human lung cells. Chem Res Toxicol 18:19–23
Karlsson HL, Ljungman AG, Lindbom J et al (2006) Comparison of genotoxic and inflammatory effects of particles generated by wood combustion, a road simulator and collected from street and subway. Toxicol Lett 165:203–211
Karlsson HL, Cronholm P, Gustafsson J et al (2008a) Copper oxide nanoparticles are highly toxic: a comparison between metal oxide nanoparticles and carbon nanotubes. Chem Res Toxicol 21:1726–1732
Karlsson HL, Holgersson A, Moller L (2008b) Mechanisms related to the genotoxicity of particles in the subway and from other sources. Chem Res Toxicol 21:726–731
Kato T, Yashiro T, Murata Y et al (2003) Evidence that exogenous substances can be phagocytized by alveolar epithelial cells and transported into blood capillaries. Cell Tissue Res 311:47–51
Kawakami K, Iwamura A, Goto E et al (1990) Kinetics and clinical application of 99mTc-Technegas. Kaku Igaku (Japan) 27:725–733
Kemp SJ, Thorley AJ, Gorelik J et al (2008) Immortalization of human alveolar epithelial cells to investigate nanoparticle uptake. Am J Respir Cell Mol Biol 39:591–597
Kim KJ, Crandall ED (1983) Heteropore populations of bullfrog alveolar epithelium. J Appl Physiol 54:140–146
Kim KJ, Crandall ED (1996) Models for investigation of peptide and protein transport across cultured mammalian respiratory epithelial barriers. Pharm Biotechnol 8:325–346
Kim KJ, Malik AB (2003) Protein transport across the lung epithelial barriers. Am J Physiol Lung Cell Mol Physiol 284:L247–L259
Kim KJ, Matsukawa Y, Yamahara H et al (2003) Absorption of intact albumin across rat alveolar epithelial cell monolayers. Am J Physiol Lung Cell Mol Physiol 284:L458–L465
Kim KJ, Fandy TE, Lee VH et al (2004) Net absorption of IgG via FcRn-mediated transcytosis across rat alveolar epithelial cell monolayers. Am J Physiol Lung Cell Mol Physiol 287:L616–L622
Kleinstreuer C, Zhang Z, Donohue JF (2008) Targeted drug-aerosol delivery in the human respiratory system. Annu Rev Biomed Eng 10:195–220
Knol AB, de Hartog JJ, Boogaard H et al (2009) Expert elicitation on ultrafine particles: likelihood of health effects and causal pathways. Part Fibre Toxicol 6:19
Konig MF, Lucocq JM, Weibel ER (1993) Demonstration of pulmonary vascular perfusion by electron and light microscopy. J Appl Physiol 75:1877–1883
Kreyling WG, Semmler M, Erbe F et al (2002) Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low. J Toxicol Environ Health A 65:1513–1530
Kreyling WG, Semmler-Behnke M, Moller W (2006a) Health implications of nanoparticles. J Nanopart Res 8:543–562
Kreyling WG, Semmler-Behnke M, Moller W (2006b) Ultrafine particle-lung interactions: does size matter? J Aerosol Med 19:74–83
Kreyling WG, Semmler-Behnke M, Seitz J et al (2009) Size dependence of the translocation of inhaled iridium and carbon nanoparticle aggregates from the lung of rats to the blood and secondary target organs. Inhal Toxicol 21(Suppl 1):55–60
Kroto HW, Heath JR, O’Brien S et al (1985) C60-Buckminsterfullerene. Nature 318:162–163
Lam HF, Chen LC, Ainsworth D et al (1988) Pulmonary function of guinea pigs exposed to freshly generated ultrafine zinc oxide with and without spike concentrations. Am Ind Hyg Assoc J 49:333–341
Lam CW, James JT, McCluskey R et al (2004) Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol Sci 77:126–134
Lam CW, James JT, McCluskey R et al (2006) A review of carbon nanotube toxicity and assessment of potential occupational and environmental health risks. Crit Rev Toxicol 36:189–217
Law WC, Yong KT, Roy I et al (2009) Aqueous-phase synthesis of highly luminescent CdTe/ZnTe core/shell quantum dots optimized for targeted bioimaging. Small 5:1302–1310
Lewinski N, Colvin V, Drezek R (2008) Cytotoxicity of nanoparticles. Small 4:26–49
Li D, He Q, Cui Y et al (2007) Immobilization of glucose oxidase onto gold nanoparticles with enhanced thermostability. Biochem Biophys Res Commun 355:488–493
Liao D, Creason J, Shy C et al (1999) Daily variation of particulate air pollution and poor cardiac autonomic control in the elderly. Environ Health Perspect 107:521–525
Lin P, Chen JW, Chang LW et al (2008) Computational and ultrastructural toxicology of a nanoparticle, Quantum Dot 705, in mice. Environ Sci Technol 42:6264–6270
Lok CN, Ho CM, Chen R et al (2007) Silver nanoparticles: partial oxidation and antibacterial activities. J Biol Inorg Chem 12:527–534
Lovric J, Bazzi HS, Cuie Y et al (2005a) Differences in subcellular distribution and toxicity of green and red emitting CdTe quantum dots. J Mol Med 83:377–385
Lovric J, Cho SJ, Winnik FM et al (2005b) Unmodified cadmium telluride quantum dots induce reactive oxygen species formation leading to multiple organelle damage and cell death. Chem Biol 12:1227–1234
Male KB, Lachance B, Hrapovic S et al (2008) Assessment of cytotoxicity of quantum dots and gold nanoparticles using cell-based impedance spectroscopy. Anal Chem 80:5487–5493
Matsukawa Y, Lee VH, Crandall ED et al (1997) Size-dependent dextran transport across rat alveolar epithelial cell monolayers. J Pharm Sci 86:305–309
McIntosh CM, Esposito EA 3 rd, Boal AK et al (2001) Inhibition of DNA transcription using cationic mixed monolayer protected gold clusters. J Am Chem Soc 123:7626–7629
Mecke A, Majoros IJ, Patri AK et al (2005) Lipid bilayer disruption by polycationic polymers: the roles of size and chemical functional group. Langmuir 21:10348–10354
Mehta D, Bhattacharya J, Matthay MA et al (2004) Integrated control of lung fluid balance. Am J Physiol Lung Cell Mol Physiol 287:L1081–L1090
Moghimi SM, Hunter AC (2001) Capture of stealth nanoparticles by the body’s defences. Crit Rev Ther Drug Carrier Syst 18:527–550
Moghimi SM, Hunter AC, Murray JC (2001) Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev 53:283–318
Moghimi SM, Hunter AC, Murray JC (2005) Nanomedicine: current status and future prospects. FASEB J 19:311–330
Monteiro-Riviere NA, Tran CL (2007) Nanotoxicology: characterization, dosing, and health effects. Informa Healthcare, New York
Moon MH, Kang D, Jung J et al (2004) Separation of carbon nanotubes by frit inlet asymmetrical flow field-flow fractionation. J Sep Sci 27:710–717
Muhlfeld C, Rothen-Rutishauser B, Blank F et al (2008) Interactions of nanoparticles with pulmonary structures and cellular responses. Am J Physiol Lung Cell Mol Physiol 294:L817–L829
Muller J, Huaux F, Moreau N et al (2005) Respiratory toxicity of multi-wall carbon nanotubes. Toxicol Appl Pharmacol 207:221–231
Muller J, Decordier I, Hoet PH et al (2008a) Clastogenic and aneugenic effects of multi-wall carbon nanotubes in epithelial cells. Carcinogenesis 29:427–433
Muller J, Huaux F, Fonseca A et al (2008b) Structural defects play a major role in the acute lung toxicity of multiwall carbon nanotubes: toxicological aspects. Chem Res Toxicol 21:1698–1705
Mutlu GM, Green D, Bellmeyer A et al (2007) Ambient particulate matter accelerates coagulation via an IL-6-dependent pathway. J Clin Invest 117:2952–2961
Mutlu GM, Budinger GR, Green AA et al (2010) Biocompatible nanoscale dispersion of single-walled carbon nanotubes minimizes in vivo pulmonary toxicity. Nano Lett 10(5):1664–1667
Nel A, Xia T, Madler L et al (2006) Toxic potential of materials at the nanolevel. Science 311:622–627
Nemmar A, Vanbilloen H, Hoylaerts MF et al (2001) Passage of intratracheally instilled ultrafine particles from the lung into the systemic circulation in hamster. Am J Respir Crit Care Med 164:1665–1668
Nemmar A, Hoet PH, Vanquickenborne B et al (2002) Passage of inhaled particles into the blood circulation in humans. Circulation 105:411–414
Nemmar A, Hoylaerts MF, Hoet PH et al (2003) Size effect of intratracheally instilled particles on pulmonary inflammation and vascular thrombosis. Toxicol Appl Pharmacol 186:38–45
Nemmar A, Hoylaerts MF, Hoet PH et al (2004) Possible mechanisms of the cardiovascular effects of inhaled particles: systemic translocation and prothrombotic effects. Toxicol Lett 149:243–253
Niemeyer CM, Mirkin CA (2004) Nanobiotechnology. Wiley-VCH, Weinheim
Oberdorster G (2000) Acute pulmonary effects of ultrafine particles in rats and mice. Health Effects Institute, Cambridge
Oberdorster G (2001) Pulmonary effects of inhaled ultrafine particles. Int Arch Occup Environ Health 74:1–8
Oberdorster G (2002) Toxicokinetics and effects of fibrous and nonfibrous particles. Inhal Toxicol 14:29–56
Oberdorster G, Ferin J, Gelein R et al (1992) Role of the alveolar macrophage in lung injury: studies with ultrafine particles. Environ Health Perspect 97:193–199
Oberdorster G, Ferin J, Lehnert BE (1994) Correlation between particle size, in vivo particle persistence, and lung injury. Environ Health Perspect 102(Suppl 5):173–179
Oberdorster G, Gelein RM, Ferin J et al (1995) Association of particulate air pollution and acute mortality: involvement of ultrafine particles? Inhal Toxicol 7:111–124
Oberdorster G, Sharp Z, Atudorei V et al (2002) Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J Toxicol Environ Health A 65:1531–1543
Oberdorster G, Sharp Z, Atudorei V et al (2004) Translocation of inhaled ultrafine particles to the brain. Inhal Toxicol 16:437–445
Oberdorster G, Maynard A, Donaldson K et al (2005a) Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol 2:8
Oberdorster G, Oberdorster E, Oberdorster J (2005b) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–839
Orr G, Panther DJ, Cassens KJ et al (2009) Syndecan-1 mediates the coupling of positively charged submicrometer amorphous silica particles with actin filaments across the alveolar epithelial cell membrane. Toxicol Appl Pharmacol 236:210–220
Park S, Lee YK, Jung M et al (2007) Cellular toxicity of various inhalable metal nanoparticles on human alveolar epithelial cells. Inhal Toxicol 19(Suppl 1):S59–S65
Partha R, Lackey M, Hirsch A et al (2007) Self assembly of amphiphilic C60 fullerene derivatives into nanoscale supramolecular structures. J Nanobiotechnology 5:6
Peters A, Liu E, Verrier RL et al (2000) Air pollution and incidence of cardiac arrhythmia. Epidemiology 11:11–17
Peters A, Frohlich M, Doring A et al (2001) Particulate air pollution is associated with an acute phase response in men; results from the MONICA-Augsburg Study. Eur Heart J 22:1198–1204
Pietropaoli AP, Frampton MW, Hyde RW et al (2004) Pulmonary function, diffusing capacity, and inflammation in healthy and asthmatic subjects exposed to ultrafine particles. Inhal Toxicol 16(Suppl 1):59–72
Politis M, Pilinis C, Lekkas TD (2008) Ultrafine particles (UFP) and health effects. Dangerous. Like no other PM? Review and analysis. Global NEST J 10:439–452
Porter AE, Muller K, Skepper J et al (2006) Uptake of C60 by human monocyte macrophages, its localization and implications for toxicity: studied by high resolution electron microscopy and electron tomography. Acta Biomater 2:409–419
Porter AE, Gass M, Bendall JS et al (2009) Uptake of noncytotoxic acid-treated single-walled carbon nanotubes into the cytoplasm of human macrophage cells. ACS Nano 3:1485–1492
Rejman J, Oberle V, Zuhorn IS et al (2004) Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis. Biochem J 377:159–169
Ryman-Rasmussen JP, Riviere JE, Monteiro-Riviere NA (2007a) Surface coatings determine cytotoxicity and irritation potential of quantum dot nanoparticles in epidermal keratinocytes. J Invest Dermatol 127:143–153
Ryman-Rasmussen JP, Riviere JE, Monteiro-Riviere NA (2007b) Variables influencing interactions of untargeted quantum dot nanoparticles with skin cells and identification of biochemical modulators. Nano Lett 7:1344–1348
Sauer UG (2009) Animal and non-animal experiments in nanotechnology—the results of a critical literature survey. ALTEX 26:109–128
Sayes CM, Fortner JD, Guo W et al (2004) The differential cytotoxicity of water-soluble fullerenes. Nano Lett 4:1881–1887
Sayes CM, Gobin AM, Ausman KD et al (2005) Nano-C60 cytotoxicity is due to lipid peroxidation. Biomaterials 26:7587–7595
Sayes CM, Marchione AA, Reed KL et al (2007a) Comparative pulmonary toxicity assessments of C60 water suspensions in rats: few differences in fullerene toxicity in vivo in contrast to in vitro profiles. Nano Lett 7:2399–2406
Sayes CM, Reed KL, Warheit DB (2007b) Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. Toxicol Sci 97:163–180
Schlesinger PA, Stillman MT, Peterson L (1982) Polyarthritis with birefringent lipid within synovial fluid macrophages: case report and ultrastructural study. Arthritis Rheum 25:1365–1368
Scrivens W, Tour JM (1994) Synthesis of 14 C-labeled C60, its suspension in water, and its uptake by human keratinocytes. J Am Chem Soc 116:4517–4518
Semmler-Behnke M, Takenaka S, Fertsch S et al (2007) Efficient elimination of inhaled nanoparticles from the alveolar region: evidence for interstitial uptake and subsequent reentrainment onto airway epithelium. Environ Health Perspect 115:728–733
Shiohara A, Hoshino A, Hanaki K et al (2004) On the cyto-toxicity caused by quantum dots. Microbiol Immunol 48:669–675
Shvedova AA, Castranova V, Kisin ER et al (2003) Exposure to carbon nanotube material: assessment of nanotube cytotoxicity using human keratinocyte cells. J Toxicol Environ Health A 66:1909–1926
Shvedova AA, Kisin ER, Mercer R et al (2005) Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am J Physiol Lung Cell Mol Physiol 289:L698–L708
Shvedova AA, Fabisiak JP, Kisin ER et al (2008) Sequential exposure to carbon nanotubes and bacteria enhances pulmonary inflammation and infectivity. Am J Respir Cell Mol Biol 38:579–590
Silva VM, Corson N, Elder A et al (2005) The rat ear vein model for investigating in vivo thrombogenicity of ultrafine particles (UFP). Toxicol Sci 85:983–989
Singh R, Pantarotto D, Lacerda L et al (2006) Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers. Proc Natl Acad Sci USA 103:3357–3362
Smart SK, Cassady AI, Lu GQ et al (2006) The biocompatibility of carbon nanotubes. Carbon 44:1034–1047
Soto K, Garza KM, Murr LE (2007) Cytotoxic effects of aggregated nanomaterials. Acta Biomater 3:351–358
Spohn P, Hirsch C, Hasler F et al (2009) C60 fullerene: a powerful antioxidant or a damaging agent? The importance of an in-depth material characterization prior to toxicity assays. Environ Pollut 157:1134–1139
Stern ST, Zolnik BS, McLeland CB et al (2008) Induction of autophagy in porcine kidney cells by quantum dots: a common cellular response to nanomaterials? Toxicol Sci 106:140–152
Storm G, Belliot SO, Daemen T et al (1995) Surface modification of nanoparticles to oppose uptake by the mononuclear phagocyte system. Adv Drug Deliv Rev 17:31–48
Su Y, He Y, Lu H et al (2009) The cytotoxicity of cadmium based, aqueous phase—synthesized, quantum dots and its modulation by surface coating. Biomaterials 30:19–25
Takenaka S, Karg E, Roth C et al (2001) Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats. Environ Health Perspect 109(Suppl 4):547–551
Takenaka S, Karg E, Kreyling WG et al (2004) Fate and toxic effects of inhaled ultrafine cadmium oxide particles in the rat lung. Inhal Toxicol 16(Suppl 1):83–92
Takenaka S, Karg E, Kreyling WG et al (2006) Distribution pattern of inhaled ultrafine gold particles in the rat lung. Inhal Toxicol 18:733–740
Timonen KL, Vanninen E, de Hartog J et al (2006) Effects of ultrafine and fine particulate and gaseous air pollution on cardiac autonomic control in subjects with coronary artery disease: the ULTRA study. J Expo Sci Environ Epidemiol 16:332–341
Tokuyama H, Yamago S, Nakamura E et al (1993) Photoinduced biochemical activity of fullerene carboxylic acid. J Am Chem Soc 115:7918–7919
Usenko CY, Harper SL, Tanguay RL (2008) Fullerene C60 exposure elicits an oxidative stress response in embryonic zebrafish. Toxicol Appl Pharmacol 229:44–55
Wagner AJ, Bleckmann CA, Murdock RC et al (2007) Cellular interaction of different forms of aluminum nanoparticles in rat alveolar macrophages. J Phys Chem B 111:7353–7359
Wallace WE, Keane MJ, Murray DK, et al (2007) Phospholipid lung surfactant and nanoparticle surface toxicity: lessons from diesel soots and silicate dusts. J Nanopart Res 9:23–38
Wang H, Wang J, Deng X et al (2004) Biodistribution of carbon single-wall carbon nanotubes in mice. J Nanosci Nanotechnol 4:1019–1024
Wang L, Wang K, Santra S et al (2006) Watching silica nanoparticles glow in the biological world. Anal Chem 78:646–654
Wang Y, Camargo PH, Skrabalak SE et al (2008) A facile, water-based synthesis of highly branched nanostructures of silver. Langmuir 24:12042–12046
Warheit DB (2006) What is currently known about the health risks related to carbon nanotube exposures? Carbon 44:1064–1069
Warheit DB, Sayes CM, Reed KL et al (2008) Health effects related to nanoparticle exposures: environmental, health and safety considerations for assessing hazards and risks. Pharmacol Ther 120:35–42
Wick P, Manser P, Limbach LK et al (2007) The degree and kind of agglomeration affect carbon nanotube cytotoxicity. Toxicol Lett 168:121–131
Widera A, Beloussow K, Kim KJ et al (2003a) Phenotype-dependent synthesis of transferrin receptor in rat alveolar epithelial cell monolayers. Cell Tissue Res 312:313–318
Widera A, Kim KJ, Crandall ED et al (2003b) Transcytosis of GCSF-transferrin across rat alveolar epithelial cell monolayers. Pharm Res 20:1231–1238
Wiseman DA, Wells SM, Wilham J et al (2006) Endothelial response to stress from exogenous Zn2+ resembles that of NO-mediated nitrosative stress, and is protected by MT-1 overexpression. Am J Physiol 291:C555–C568
Wright EM, Pietras RJ (1974) Routes of nonelectrolyte permeation across epithelial membranes. J Membr Biol 17:293–312
Xia T, Kovochich M, Brant J et al (2006) Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Lett 6:1794–1807
Xia T, Kovochich M, Liong M et al (2008) Cationic polystyrene nanosphere toxicity depends on cell-specific endocytic and mitochondrial injury pathways. ACS Nano 2:85–96
Xia T, Li N, Nel AE (2009) Potential health impact of nanoparticles. Annu Rev Public Health 30:137–150
Xu Z, Hu PA, Wang S et al (2008) Biological functionalization and fluorescent imaging of carbon nanotubes. Appl Surf Sci 254:1915–1918
Yacobi NR, Phuleria HC, Demaio L et al (2007) Nanoparticle effects on rat alveolar epithelial cell monolayer barrier properties. Toxicol In Vitro 21:1373–1381
Yacobi NR, Demaio L, Xie J et al (2008) Polystyrene nanoparticle trafficking across alveolar epithelium. Nanomedicine 4:139–145
Yacobi NR, Malmstadt N, Fazlollahi F et al (2010) Mechanisms of alveolar epithelial translocation of a defined population of nanoparticles. Am J Respir Cell Mol Biol 42:604–614
Yamago S, Tokuyama H, Nakamura E et al (1995) In vivo biological behavior of a water-miscible fullerene: 14C labeling, absorption, distribution, excretion and acute toxicity. Chem Biol 2:385–389
Yamawaki H, Iwai N (2006) Cytotoxicity of water-soluble fullerene in vascular endothelial cells. Am J Physiol Cell Physiol 290:C1495–C1502
Yang W, Peters JI, Williams RO 3rd (2008) Inhaled nanoparticles—a current review. Int J Pharm 356:239–247
Zhang T, Stilwell JL, Gerion D et al (2006) Cellular effect of high doses of silica-coated quantum dot profiled with high throughput gene expression analysis and high content cellomics measurements. Nano Lett 6:800–808
Acknowledgements
This work was supported in part by Hasting Foundation, Whittier Foundation, and research grants from the National Institutes of Health (ES017034, ES018782, HL038578, HL038621, HL062569, HL064365, and HL089445). Zea Borok is Ralph Edgington Chair in Medicine and Edward D. Crandall is Hastings Professor and Kenneth T. Norris Jr. Chair of Medicine.
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Yacobi, N.R., Fazllolahi, F., Kim, Y.H. et al. Nanomaterial interactions with and trafficking across the lung alveolar epithelial barrier: implications for health effects of air-pollution particles. Air Qual Atmos Health 4, 65–78 (2011). https://doi.org/10.1007/s11869-010-0098-z
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DOI: https://doi.org/10.1007/s11869-010-0098-z