journal article·2011-01Open access

Internalisation of engineered nanoparticles into mammalian cells in vitro: influence of cell type and particle properties

Wibke Busch, Susanne Bastian, Ulrike Trahorsch, Maria Iwe, Dana Kühnel, Tobias Meißner, Armin Springer, Michael Gelinsky, Volkmar Richter, Chrysanthy Ikonomidou, Annegret Potthoff, Irina Lehmann, Kristin Schirmer

Journal of Nanoparticle Research· Volume 13· Issue 1

Abstract

Cellular internalisation of industrial engineered nanoparticles is undesired and a reason for concern. Here we investigated and compared the ability of seven different mammalian cell cultures in vitro to incorporate six kinds of engineered nanoparticles, focussing on the role of cell type and particle properties in particle uptake. Uptake was examined using light and electron microscopy coupled with energy dispersive X-ray spectroscopy (EDX) for particle element identification. Flow cytometry was applied for semi-quantitative analyses of particle uptake and for exploring the influence on uptake by the phagocytosis inhibitor Cytochalasin D (CytoD). All particles studied were found to enter each kind of cultured cells. Yet, particles were never found within cell nuclei. The presence of the respective particles within the cells was confirmed by EDX. Live-cell imaging revealed the time-dependent process of internalisation of technical nanoparticles, which was exemplified by tungsten carbide particle uptake into the human skin cells, HaCaT. Particles were found to co-localise with lysosomal structures within the cells. The incorporated nanoparticles changed the cellular granularity, as measured by flow cytometry, already after 3 h of exposure in a particle specific manner. By correlating particle properties with flow cytometry data, only the primary particle size was found to be a weakly influential property for particle uptake. CytoD, an inhibitor of actin filaments and therewith of phagocytosis, significantly inhibited the internalisation of particle uptake in only two of the seven investigated cell cultures. Our study, therefore, supports the notion that nanoparticles can enter mammalian cells quickly and easily, irrespective of the phagocytic ability of the cells.
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Research context

OpenAlex topics: Nanoparticles: synthesis and applications · Nanoparticle-Based Drug Delivery

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References (45)

Show source-provided references
1. Ashwood P, Thompson RP, Powell JJ (2007) Fine particles that adsorb lipopolysaccharide via bridging calcium cations may mimic bacterial pathogenicity towards cells. Exp Biol Med 232:107–117
2. Bao L, Chen S, Wu L, Hei TK, Wu Y, Yu Z, Xu A (2007) Mutagenicity of diesel exhaust particles mediated by cell–particle interaction in mammalian cells. Toxicology 229:91–10010.1016/j.tox.2006.10.007 ↗
3. Bastian S, Busch W, Kühnel D, Springer A, Meißner T, Holke R, Scholz S, Iwe M, Pompe W, Gelinsky M, Potthoff A, Richter V, Ikonomidou C, Schirmer K (2009) Toxicity of tungsten carbide and cobalt-doped tungsten carbide nanoparticles in mammalian cells in vitro. Environ Health Perspect 117:530–53610.1289/ehp.0901615 ↗
4. Baun A, Sorensen SN, Rasmussen RF, Hartmann NB, Koch CB (2008) Toxicity and bioaccumulation of xenobiotic organic compounds in the presence of aqueous suspensions of aggregates of nano-C(60). Aquat Toxicol 86:379–38710.1016/j.aquatox.2007.11.019 ↗
5. Bhattacharya K, Davoren M, Boertz J, Schins R, Hoffmann E, Dopp E (2009) Titanium dioxide nanoparticles induce oxidative stress and DNA-adduct formation but not DNA-breakage in human lung cells. Part Fibre Toxicol 6:1710.1186/1743-8977-6-17 ↗
6. Busch W, Kühnel D, Schirmer K, Scholz S (2010) Tungsten carbide cobalt nanoparticles exert hypoxia-like effects on the gene expression level in human keratinocytes. BMC Genomics 11:6510.1186/1471-2164-11-65 ↗
7. Cedervall T, Lynch I, Lindman S, Berggard T, Thulin E, Nilsson H, Dawson KA, Linse S (2007) Understanding the nanoparticle–protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. Proc Natl Acad Sci USA 104:2050–205510.1073/pnas.0608582104 ↗
8. Chang GH, Barbaro NM, Pieper RO (2000) Phosphatidylserine-dependent phagocytosis of apoptotic glioma cells by normal human microglia, astrocytes, and glioma cells. Neuro Oncol 2:174–18310.1093/neuonc/2.3.174 ↗
9. Chen M, von Mikecz A (2005) Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles. Exp Cell Res 305:51–6210.1016/j.yexcr.2004.12.021 ↗
10. Chithrani BD, Ghazani AA, Chan WC (2006) Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 6:662–66810.1021/nl052396o ↗
11. Deguchi S, Yamazaki T, Mukai SA, Usami R, Horikoshi K (2007) Stabilization of C60 nanoparticles by protein adsorption and its implications for toxicity studies. Chem Res Toxicol 20:854–85810.1021/tx6003198 ↗
12. Geiser M, Rothen-Rutishauser B, Kapp N, Schurch S, Kreyling W, Schulz H, Semmler M, Im Hof V, Heyder J, Gehr P (2005) Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells. Environ Health Perspect 113:1555–156010.1289/ehp.8006 ↗
13. Gojova A, Guo B, Kota RS, Rutledge JC, Kennedy IM, Barakat AI (2007) Induction of inflammation in vascular endothelial cells by metal oxide nanoparticles: effect of particle composition. Environ Health Perspect 115:403–40910.1289/ehp.8497 ↗
14. Gratton SE, Ropp PA, Pohlhaus PD, Luft JC, Madden VJ, Napier ME, DeSimone JM (2008) The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci USA 105:11613–1161810.1073/pnas.0801763105 ↗
15. Haberzettl P, Duffin R, Kramer U, Hohr D, Schins RP, Borm PJ, Albrecht C (2007) Actin plays a crucial role in the phagocytosis and biological response to respirable quartz particles in macrophages. Arch Toxicol 81:459–47010.1007/s00204-007-0178-5 ↗
16. Harush-Frenkel O, Rozentur E, Benita S, Altschuler Y (2008) Surface charge of nanoparticles determines their endocytic and transcytotic pathway in polarized MDCK cells. Biomacromolecules 9:435–44310.1021/bm700535p ↗
17. Hildebrand H, Kühnel D, Potthoff A, Mackenzie K, Springer A, Schirmer K (2009) Evaluating the cytotoxicity of palladium/magnetite nano-catalysts intended for wastewater treatment. Environ Pollut 158:65–7310.1016/j.envpol.2009.08.021 ↗
18. Johnsen S, Widder EA (1999) The physical basis of transparency in biological tissue: ultrastructure and the minimization of light scattering. J Theor Biol 199:181–19810.1006/jtbi.1999.0948 ↗
19. Kaksonen M, Toret CP, Drubin DG (2006) Harnessing actin dynamics for clathrin-mediated endocytosis. Nat Rev Mol Cell Biol 7:404–41410.1038/nrm1940 ↗
20. Kanno S, Furuyama A, Hirano S (2007) A murine scavenger receptor MARCO recognizes polystyrene nanoparticles. Toxicol Sci 97:398–40610.1093/toxsci/kfm050 ↗
21. Kreuter J, Shamenkov D, Petrov V, Ramge P, Cychutek K, Koch-Brandt C, Alyautdin R (2002) Apolipoprotein-mediated transport of nanoparticle-bound drugs across the blood–brain barrier. J Drug Target 10:317–32510.1080/10611860290031877 ↗
22. Kühnel D, Busch W, Meißner T, Springer A, Potthoff A, Richter V, Gelinsky M, Scholz S, Schirmer K (2009) Agglomeration of tungsten carbide nanoparticles in exposure medium does not prevent uptake and toxicity toward a rainbow trout gill cell line. Aquat Toxicol 93:91–9910.1016/j.aquatox.2009.04.003 ↗
23. Limbach LK, Li Y, 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 39:9370–937610.1021/es051043o ↗
24. Long TC, Saleh N, Tilton RD, Lowry GV, Veronesi B (2006) Titanium dioxide (P25) produces reactive oxygen species in immortalized brain microglia (BV2): implications for nanoparticle neurotoxicity. Environ Sci Technol 40:4346–435210.1021/es060589n ↗
25. Lundqvist M, Stigler J, Elia G, Lynch I, Cedervall T, Dawson KA (2008) Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts. Proc Natl Acad Sci USA 105:14265–1427010.1073/pnas.0805135105 ↗
26. Maynard AD, Kuempel ED (2005) Airborne nanostructured particles and occupational health. J Nanopart Res 7:587–61410.1007/s11051-005-6770-9 ↗
27. Meißner T, Potthoff A, Richter V (2009) Physico-chemical characterization in the light of toxicological effects. Inhal Toxicol 21(Suppl 1):35–3910.1080/08958370902942608 ↗
28. Meißner T, Kühnel D, Busch W, Oswald S, Richter V, Michaelis A, Schirmer K, Potthoff A (2010) Physical–chemical characterization of tungsten carbide nanoparticles as a basis for toxicological investigations. Nanotoxicology 4:196–20610.3109/17435391003605455 ↗
29. Naß R, Albayrak S, Aslan M, Schmidt H (1994) Colloidal processing and sintering of nano-scale TiN. In: 5th international conference in ceramic processing, science and technology. Friedrichshafen, Germany
30. Oh JM, Choi SJ, Lee GE, Kim JE, Choy JH (2009) Inorganic metal hydroxide nanoparticles for targeted cellular uptake through clathrin-mediated endocytosis. Chem Asian J 4:67–7310.1002/asia.200800290 ↗
31. Papis E, Rossi F, Raspanti M, Dalle-Donne I, Colombo G, Milzani A, Bernardini G, Gornati R (2009) Engineered cobalt oxide nanoparticles readily enter cells. Toxicol Lett 189:253–25910.1016/j.toxlet.2009.06.851 ↗
32. Potthoff A, Meißner T, Richter V, Busch W, Kühnel D, Bastian S, Iwe M, Springer A (2009) Evaluation of health risks of nanoparticles—a contribution to a sustainable development of nanotechnology. Solid State Phenom 151:183–18910.4028/www.scientific.net/SSP.151.183 ↗
33. Razani B, Woodman SE, Lisanti MP (2002) Caveolae: from cell biology to animal physiology. Pharmacol Rev 54:431–46710.1124/pr.54.3.431 ↗
34. Rejman J, Oberle V, Zuhorn IS, Hoekstra D (2004) Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis. Biochem J 377:159–16910.1042/bj20031253 ↗
35. Reyes L, Davidson MK, Thomas LC, Davis JK (1999) Effects of Mycoplasma fermentans incognitus on differentiation of THP-1 cells. Infect Immun 67:3188–319210.1128/IAI.67.7.3188-3192.1999 ↗
36. Roldan A, Gogg S, Ferrini M, Schillaci R, De Nicola AF (1997) Glucocorticoid regulation of in vitro astrocyte phagocytosis. Biocell 21:83–89
37. Schubert W, Frank PG, Razani B, Park DS, Chow CW, Lisanti MP (2001) Caveolae-deficient endothelial cells show defects in the uptake and transport of albumin in vivo. J Biol Chem 276:48619–4862210.1074/jbc.C100613200 ↗
38. Spurr AR (1969) A low-viscosity epoxy resin embedding medium for electron microscopy. J Ultrastruct Res 26:31–4310.1016/S0022-5320(69)90033-1 ↗
39. Stearns R, Paulauskis J, Godleski J (2001) Endocytosis of ultrafine particles by A549 cells. Am J Respir Cell Mol Biol 24:108–11510.1165/ajrcmb.24.2.4081 ↗
40. Stoeger T, Takenaka S, Frankenberger B, Ritter B, Karg E, Maier K, Schulz H, Schmid O (2009) Deducing in vivo toxicity of combustion-derived nanoparticles from a cell-free oxidative potency assay and metabolic activation of organic compounds. Environ Health Perspect 117:54–6010.1289/ehp.11370 ↗
41. Stringer B, Imrich A, Kobzik L (1995) Flow cytometric assay of lung macrophage uptake of environmental particulates. Cytometry 20:23–3210.1002/cyto.990200106 ↗
42. Thomas EW (1992) Brain macrophages: evaluation of microglia and their functions. Brain Res Rev 17:61–7410.1016/0165-0173(92)90007-9 ↗
43. Xia T, Kovochich M, Brant J, Hotze M, Sempf J, Oberley T, Sioutas C, Yeh JI, Wiesner MR, Nel AE (2006) Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Lett 6:1794–180710.1021/nl061025k ↗
44. Yumoto R, Nishikawa H, Okamoto M, Katayama H, Nagai J, Takano M (2006) Clathrin-mediated endocytosis of FITC-albumin in alveolar type II epithelial cell line RLE-6TN. Am J Physiol Lung Cell Mol Physiol 290:L946–L95510.1152/ajplung.00173.2005 ↗
45. Zhang LW, Monteiro-Riviere NA (2009) Mechanisms of quantum dot nanoparticle cellular uptake. Toxicol Sci 110:138–15510.1093/toxsci/kfp087 ↗