Abstract
A critical view of the current toxicological methods used in nanotechnology and their related techniques. Hereby, toxicological effects derived from the intracellular accumulation and uptake will be examined. Then advantages/disadvantages of these methods will be discussed. Additional analytical techniques necessary to implement the results will be reviewed.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Service RF (2004) Nanotoxicology: nanotechnology grows up. Science 304:1732–1734
Maynard AD, Aitken RJ, Butz T, Colvin V, Donaldson K, Oberdorster G, Philbert MA, Ryan J, Seaton A, Stone V, Tinkle SS, Tran L, Walker NJ, Warheit DB (2006) Safe handling of nanotechnology. Nature 444:267–269
Hoet PH, Bruske-Hohlfeld I, Salata OV (2004) Nanoparticles – known and unknown health risks. J Nanobiotechnol 2:12
Maynard AD (2007) Nanotechnology: the next big thing, or much ado about nothing? Ann Occup Hyg 51:1–12
Donaldson K, Aitken R, Tran L, Stone V, Duffin R, Forrest G, Alexander A (2006) Carbon nanotubes: a review of their properties in relation to pulmonary toxicology and workplace safety. Toxicol Sci 92:5–22
Gaskell G, Allum N, Bauer M, Durant J, Allansdottir A, Bonfadelli H, Boy D, de Cheveigne S, Fjaestad B, Gutteling JM, Hampel J, Jelsoe E, Jesuino JC, Kohring M, Kronberger N, Midden C, Nielsen TH, Przestalski A, Rusanen T, Sakellaris G, Torgersen H, Twardowski T, Wagner W (2000) Biotechnology and the European public. Nat Biotechnol 18:935–938
Song Y, Li X, Du X (2009) Exposure to nanoparticles is related to pleural effusion, pulmonary fibrosis and granuloma. Eur Respir J 34:559–567
Oberdoerster G, Oberdoerster E, Oberdoerster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–839
Oberdorster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W, Lai D, Olin S, Monteiro-Riviere N, Warheit D, Yang H (2005) Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol 2:8
Oberdörster G, Stone V, Donaldson K (2007) Toxicology of nanoparticles: a historical perspective. Nanotoxicology 1:2–25
The Royal Society and The Royal Academy of Engineers Report (2004) Nanoscience and Nanotechnologies: Opportunites and Uncertainties
Zimmer AT, Baron PA, Biswas P (2002) The influence of operating parameters on number-weighted aerosol size distribution generated from a gas metal arc welding process. J Aerosol Sci 33:519–531
Rundell KW (2003) High levels of airborne ultrafine and fine particulate matter in indoor ice arenas. Inhal Toxicol 15:237–250
Kittelson DB, Watts WF, Johnson JP (2004) Nanoparticle emissions on Minnesota highways. Atmos Environ 38:9–19
Donaldson K, Stone V, Borm PJA, Jimenez LA, Gilmour PS, Schins RPF, Knaapen AM, Rahman I, Faux SP, Brown DM, MacNee W (2003) Oxidative stress and calcium signaling in the adverse effects of environmental particles (PM10). Free Radical Biol Med 34:1369–1382
Colvin VI (2003) The potential environmental impact of engineered nanomaterials. Nat Biotechnol 21:1166–1170
Jensen AW, Wilson SR, Schuster DI (1996) Biological applications of fullerenes. Bioorg Med Chem 4:767–779
Pellegrino T, Manna L, Kudera S, Liedl T, Koktysh D, Rogach AL, Keller S, Rädler J, Natile G, Parak WJ (2004) Hydrophobic nanocrystals coated with an amphiphilic polymer shell: a general route to water soluble nanocrystals. Nano Lett 4:703–707
Gupta AK, Gupta M (2005) Cytotoxicity suppression and cellular uptake enhancement of surface modified magnetic nanoparticles. Biomaterials 26:1565–1573
Rivera Gil P, Hühn D, del Mercato LL, Sasse D, Parak WJ (2010) Nanopharmacy: inorganic nanoscale devices as vectors and active compounds. Pharmacol Res 62:115–125
Duncan R, Izzo L (2005) Dendrimer biocompatibility and toxicity. Adv Drug Deliv Rev 57:2215–2237
Sperling RA, Pellegrino T, Li JK, Chang WH, Parak WJ (2006) Electrophoretic separation of nanoparticles with a discrete number of functional groups. Adv Funct Mater 16:943–948
Lin C-AJ, Sperling RA, Li JK, Yang T-Y, Li P-Y, Zanella M, Chang WH, Parak WJ (2008) Design of an amphiphilic polymer for nanoparticle coating and functionalization. Small 4:334–341
Fernández-Argüelles MT, Yakovlev A, Sperling RA, Luccardini C, Gaillard S, Medel AS, Mallet J-M, Brochon J-C, Feltz A, Oheim M, Parak WJ (2007) Synthesis and characterization of polymer-coated quantum dots with integrated acceptor dyes as FRET-based nanoprobes. Nano Lett 7:2613–2617
Stehr J, Hrelescu C, Sperling RA, Raschke G, Wunderlich M, Nichtl A, Heindl D, Kürzinger K, Parak WJ, Klar TA, Feldmann J (2008) Gold nano-stoves for microsecond DNA melting analysis. Nano Lett 8:619–623
Nel A, Xia T, Madler L, Li N (2006) Toxic potential of materials at the nanolevel. Science 311:622–627
Knol AB, de Hartog JJ, Boogaard H, Slottje P, van der Sluijs JP, Lebret E, Cassee FR, Wardekker A, Ayres JG, Borm PJ, Brunekreef B, Donaldson K, Forastiere F, Holgate ST, Kreyling WG, Nemery B, Pekkanen J, Stone V, Wichmann HE, Hoek G (2009) Expert elicitation on ultrafine particles: likelihood of health effects and causal pathways. Part Fibre Toxicol 6:19
Baroli B (2010) Penetration of nanoplarticles and nanomaterials in the skin: fiction or reality? J Pharm Sci 99:21–50
Tinkle SS, Antonini JM, Rich BA, Roberts JR, Salmen R, DePree K, Adkins EJ (2003) Skin as a route of exposure and sensitization in chronic beryllium disease. Environ Health Perspect 111:1202–1208
Rothen-Rutishauser B, Mühlfeld C, Blank F, Musso C, Gehr P (2007) Translocation of particles and inflammatory responses after exposure to fine particles and nanoparticles in an epithelial airway model. Part Fibre Toxicol 4:9
Muhlfeld C, Rothen-Rutishauser B, Blank F, Vanhecke D, Ochs M, Gehr P (2008) Interactions of nanoparticles with pulmonary structures and cellular responses. Am J Physiol Lung Cell Mol Physiol 294:L817–L829
Rothen-Rutishauser B, Grass RN, Blank F, Limbach LK, Muehlfeld C, Brandenberger C, Raemy DO, Gehr P, Stark WJ (2009) Direct combination of nanoparticle fabrication and exposure to lung cell cultures in a closed setup as a method to simulate accidental nanoparticle exposure of humans. Environ Sci Technol 43:2634–2640
Stone V, Johnston H, Schins RPF (2009) Development of in vitro systems for nanotoxicology: methodological considerations. Crit Rev Toxicol 39:613–626
Duffin R, Tran L, Brown D, Stone V, Donaldson K (2007) Proinflammogenic effects of low-toxicity and metal nanoparticles in vivo and in vitro: highlighting the role of particle surface area and surface reactivity. Inhal Toxicol 19:849–856
Gurr JR, Wang ASS, Chen CH, Jan KY (2005) Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. Toxicology 213:66–73
Limbach LK, Li YC, Grass RN, Brunner TJ, Hintermann MA, Muller M, Gunther D, Stark WJ (2005) Oxide nanoparticle uptake in human lung fibroblasts: effects of particle size, agglomeration, and diffusion at low concentrations. Environ Sci Technol 39:9370–9376
Stearns RC, Paulauskis JD, Godleski JJ (2001) Endocytosis of ultrafine particles by A549 cells. Am J Respir Cell Mol Biol 24:108–115
Gil J, Weibel ER (1971) Extracellular lining of bronchioles after perfusion-fixation of rat lungs for electron microscopy. Anat Rec 169:185–199
Schürch S, Gehr P, Hof VI, Geiser M, Green F (1990) Surfactant displaces particles toward the epithelium in airways and alveoli. Respir Physiol 80:17–32
Lenz AG, Karg E, Lentner B, Dittrich V, Brandenberger C, Rothen-Rutishauser B, Schulz H, Ferron GA, Schmid O (2009) A dose-controlled system for air-liquid interface cell exposure and application to zinc oxide nanoparticles. Part Fibre Toxicol 6:32
Muller L, Comte P, Czerwinski J, Kasper M, Mayer ACR, Gehr P, Burtscher H, Morin JP, Konstandopoulos A, Rothen-Rutishauser B (2010) New exposure system to evaluate the toxicity of (scooter) exhaust emissions in lung cells in vitro. Environ Sci Technol 44:2632–2638
Kreyling WG, Semmler M, Erbe F, Mayer P, Takenaka S, Schulz H, Oberdorster G, Ziesenis A (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, Möller W (2006) Ultrafine particle–lung interactions: does size matter? J Aerosol Med 19:74–83
Wick P, Malek A, Manser P, Meili D, Maeder-Althaus X, Diener L, Diener PA, Zisch A, Krug HF, von Mandach U (2010) Barrier capacity of human placenta for nanosized materials. Environ Health Perspect 118:432–436
Perry MJ, McAuliffe ME (2007) Are nanoparticles potential male reproductive toxicants? A literature review. Nanotoxicology 1:204–210
Xia T, Kovochich M, Liong M, Zink JI, Nel AE (2008) Cationic polystyrene nanosphere toxicity depends on cell-specific endocytic and mitochondrial injury pathways. ACS Nano 2:85–96
Nativo P, Prior IA, Brust M (2008) Uptake and intracellular fate of surface-modified gold nanoparticles. ACS Nano 2:1639–1644
Murphy CJ, Gole AM, Stone JW, Sisco PN, Alkilany AM, Goldsmith EC, Baxter SC (2008) Gold nanoparticles in biology: beyond toxicity to cellular imaging. Acc Chem Res 41:1721–1730
Cheng JX, Huff TB, Hansen MN, Zhao Y, Wei A (2007) Controlling the cellular uptake of gold nanorods. Langmuir 23:1596–1599
Sperling RA, Rivera Gil P, Zhang F, Zanella M, Parak WJ (2008) Biological applications of gold nanoparticles. Chem Soc Rev 37:1896–1908
Ozkan CS, Zhang Y, Yang M, Portney NG, Cui DX, Budak G, Ozbay E, Ozkan M (2008) Zeta potential: a surface electrical characteristic to probe the interaction of nanoparticles with normal and cancer human breast epithelial cells. Biomed Microdev 10:321–328
Stellacci F, Verma A (2010) Effect of surface properties on nanoparticle-cell interactions. Small 6:12–21
Ginzburg VV, Balijepalli S (2007) Modeling the thermodynamics of the interaction of nanoparticles with cell membranes. Nano Lett 7:3716–3722
Deserno M, Gelbart WM (2002) Adhesion and wrapping in colloid-vesicle complexes. J Phys Chem B 106:5543–5552
Smith KA, Jasnow D, Balazs AC (2007) Designing synthetic vesicles that engulf nanoscopic particles. J Chem Phys 127:084703
Chen HM, Langer R, Edwards DA (1997) A film tension theory of phagocytosis. J Colloid Interface Sci 190:118–133
Rimai DS, Quesnel DJ, Busnaina AA (2000) The adhesion of dry particles in the nanometer to micrometer-size range. Colloids Surf A Physicochem Eng Asp 165:3–10
Geiser M, Rothen-Rutishauser B, Kapp N, Schurch S, Kreyling W, Schulz H, Semmler M, Hof VI, Heyder J, Gehr P (2005) Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells. Environ Health Perspect 113:1555–1560
Diagaradjane P, Orenstein-Cardona JM, Colon-Casasnovas NE, Deorukhkar A, Shentu S, Kuno N, Schwartz DL, Gelovani JG, Krishnan S (2008) Imaging epidermal growth factor receptor expression in vivo: pharmacokinetic and biodistribution characterization of a bioconjugated quantum dot nanoprobe. Clin Cancer Res 14:731–741
Zhang H, Zeng X, Li Q, Gaillard-Kelly M, Wagner CR, Yee D (2009) Fluorescent tumour imaging of type I IGF receptor in vivo: comparison of antibody-conjugated quantum dots and small-molecule fluorophore. Br J Cancer 101:71–79
Tekle C, van Deurs B, Sandvig K, Iversen TG (2008) Cellular trafficking of quantum dot-ligand bioconjugates and their induction of changes in normal routing of unconjugated ligands. Nano Lett 8:1858–1865
Pawley JB (2006) Handbook of biological confocal microscopy
Tkachenko AG, Xie H, Liu Y, Coleman D, Ryan J, Glomm WR, Shipton MK, Franzen S, Feldheim DL (2004) Cellular trajectories of peptide-modified gold particle complexes: comparison of nuclear localization signals and peptide transduction domains. Bioconjugate Chem 15:482–490
Brandenberger C, Clift MJD, Vanhecke D, Muhlfeld C, Stone V, Gehr P, Rothen-Rutishauser B (2010) Intracellular imaging of nanoparticles: is it an elemental mistake to believe what you see? Part Fibre Toxicol 7:15
Egerton RF (2009) Electron energy-loss spectroscopy in the TEM. Rep Prog Phys 72:016502
Ottensmeyer FP, Andrew JW (1980) High-resolution microanalysis of biological specimens by electron-energy loss spectroscopy and by electron spectroscopic imaging. J Ultrastruct Res 72:336–348
Derfus AM, Chan WCW, Bhatia SN (2004) Probing the cytotoxicity of semiconductor quantum dots. Nano Lett 4:11–18
Feldheim DL, Ryan JA, Overton KW, Speight ME, Oldenburg CM, Loo L, Robarge W, Franzen S (2007) Cellular uptake of gold nanoparticles passivated with BSA-SV40 large T antigen conjugates. Anal Chem 79:9150–9159
Chithrani BD, Ghazan AA, Chan CW (2006) Determining the size and the shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 6:662–668
Tarloff JB, Kendig DM (2007) Inactivation of lactate dehydrogenase by several chemicals: implications for in vitro toxicology studies. Toxicol In Vitro 21:125–132
Henderson RF, Benson JM, Hahn FF, Hobbs CH, Jones RK, Mauderly JL, Mcclellan RO, Pickrell JA (1985) New approaches for the evaluation of pulmonary toxicity - bronchoalveolar lavage fluid analysis. Fundam Appl Toxicol 5:451–458
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63
MacNee W (2001) Oxidative stress and lung inflammation in airways disease. Eur J Pharmacol 429:195–207
Hissin PJ, Hilf R (1976) A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem 74:214–226
Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca-2+ indicators with greatly improved fluorescence properties. J Biol Chem 260:3440–3450
Wallin H, Jacobsen NR, Moller P, Cohn CA, Loft S, Vogel U (2008) Diesel exhaust particles are mutagenic in FE1-Muta (TM) Mouse lung epithelial cells. Mutat Res 641:54–57
Wallin H, Jacobsen NR, Pojana G, White P, Moller P, Cohn CA, Korsholm KS, Vogel U, Marcomini A, Loft S (2008) Genotoxicity, cytotoxicity, and reactive oxygen species induced by single-walled carbon nanotubes and C-60 fullerenes in the FE1-Muta (TM) mouse lung epithelial cells. Environ Mol Mutagen 49:476–487
Singh NP, Mccoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low-levels of DNA damage in individual cells. Exp Cell Res 175:184–191
Schins RPF, Li H, Van Berlo D, Shi T, Spelt G, Knaapen AM, Borm PJA, Albrecht C (2008) Curcumin protects against cytotoxic and inflammatory effects of quartz particles but causes oxidative DNA damage in a rat lung epithelial cell line. Toxicol Appl Pharmacol 227:115–124
Ames BN, Lee FD, Durston WE (1973) An improved bacterial test system for the detection and classification of mutagens and carcinogens. Proc Natl Acad Sci USA 70:782–786
Zhao HW, Barger MW, Ma JKH, Castranova V, Ma JYC (2004) Effects of exposure to diesel exhaust particles (DEP) on pulmonary metabolic activation of mutagenic agents. Mutat Res 564:103–113
Schins RPF, Knaapen AM (2007) Genotoxicity of poorly soluble particles. Inhal Toxicol 19:189–198
Marquis BJ, Love SA, Braun KL, Haynes CL (2009) Analytical methods to assess nanoparticle toxicity. Analyst 134:425–439
Hauck TS, Ghazani AA, Chan WCW (2008) Assessing the effect of surface chemistry on gold nanorod uptake, toxicity, and gene expression in mammalian cells. Small 4:153–159
Zhang TT, Stilwell JL, Gerion D, Ding LH, Elboudwarej O, Cooke PA, Gray JW, Alivisatos AP, Chen FF (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
Jan E, Byrne SJ, Cuddihy M, Davies AM, Volkov Y, Gun’ko YK, Kotov NA (2008) High-content screening as a universal tool for fingerprinting of cytotoxicity of nanoparticles. ACS Nano 2:928–938
Rivera Gil P, Yang F, Thomas H, Li L, Terfort A, Parak WJ (2011) Development of an assay based on cell counting with quantum dot labels for comparing cell adhesion within cocultures. Nano Today 6:20–27
Kirchner C, Liedl T, Kudera S, Pellegrino T, Javier AM, Gaub HE, Stölzle S, Fertig N, Parak WJ (2005) Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. Nano Lett 5:331–338
Oberdorster G (2010) Safety assessment for nanotechnology and nanomedicine: concepts of nanotoxicology. J Intern Med 267:89–105
Bouwmeester H, Lynch I, Marvin HJ, Dawson KA, Berges M, Braguer D, Byrne HJ, Casey A, Chambers G, Clift MJ, Elia G, Fernandes TF, Fjellsbo LB, Hatto P, Juillerat L, Klein C, Kreyling WG, Nickel C, Riediker M, Stone V (2011) Minimal analytical characterization of engineered nanomaterials needed for hazard assessment in biological matrices. Nanotoxicology 5:1–11
Worle-Knirsch JM, Pulskamp K, Krug HF (2006) Oops they did it again! Carbon nanotubes hoax scientists in viability assays. Nano Lett 6:1261–1268
Wick P, Manser P, Limbach LK, Dettlaff-Weglikowska U, Krumeich F, Roth S, Stark WJ, Bruinink A (2007) The degree and kind of agglomeration affect carbon nanotube cytotoxicity. Toxicol Lett 168:121–131
Rothen-Rutishauser B, Blank F, Muhlfeld C, Gehr P (2008) In vitro models of the human epithelial airway barrier to study the toxic potential of particulate matter. Expert Opin Drug Metab Toxicol 4:1075–1089
Sauer UG (2009) Animal and non-animal experiments in nanotechnology – the results of a critical literature survey. Altex-Alternativen Zu Tierexperimenten 26:109–134
Rothen-Rutishauser BM, Kiama SG, Gehr P (2005) A three-dimensional cellular model of the human respiratory tract to study the interaction with particles. Am J Respir Cell Mol Biol 32:281–289
Blank F, Rothen-Rutishauser B, Gehr P (2007) Dendritic cells and macrophages form a transepithelial network against foreign particulate antigens. Am J Respir Cell Mol Biol 36:669–677
Müller L, Riediker M, Wick P, Mohr M, Gehr P, Rothen-Rutishauser B (2010) Oxidative stress and inflammation response after nanoparticle exposure: differences between human lung cell monocultures and an advanced three-dimensional model of the human epithelial airways. Interface Focus 7:27–40
Lehmann AD, Blank F, Baum O, Gehr P, Rothen-Rutishauser BM (2009) Diesel exhaust particles modulate the tight junction protein occludin in lung cells in vitro. Part Fibre Toxicol 6:26
Rhee SW, Mahto SK, Yoon TH (2010) A new perspective on in vitro assessment method for evaluating quantum dot toxicity by using microfluidics technology. Biomicrofluidics 4
Thorsen T, Wang ZH, Kim MC, Marquez M (2007) High-density microfluidic arrays for cell cytotoxicity analysis. Lab Chip 7:740–745
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Rivera_Gil, P., Clift, M.J.D., Rutishauser, B.R., Parak, W.J. (2012). Methods for Understanding the Interaction Between Nanoparticles and Cells. In: Reineke, J. (eds) Nanotoxicity. Methods in Molecular Biology, vol 926. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-002-1_3
Download citation
DOI: https://doi.org/10.1007/978-1-62703-002-1_3
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-001-4
Online ISBN: 978-1-62703-002-1
eBook Packages: Springer Protocols