Advertisement

Analytical and Bioanalytical Chemistry

, Volume 408, Issue 21, pp 5935–5943 | Cite as

The interaction of an amino-modified ZrO2 nanomaterial with macrophages—an in situ investigation by Raman microspectroscopy

  • Anja Silge
  • Thomas Bocklitz
  • Rainer Ossig
  • Jürgen Schnekenburger
  • Petra Rösch
  • Jürgen Popp
Research Paper

Abstract

Metal oxide nanoparticles (NP) are applied in the fields of biomedicine, pharmaceutics, and in consumer products as textiles, cosmetics, paints, or fuels. In this context, the functionalization of the NP surface is a common method to modify and modulate the product performance. A chemical surface modification of NP such as an amino-functionalization can be used to achieve a positively charged and hydrophobic surface. Surface functionalization is known to affect the interaction of nanomaterials (NM) with cellular macromolecules and the responses of tissues or cells, like the uptake of particles by phagocytic cells. Therefore, it is important to assess the possible risk of those modified NP for human health and environment. By applying Raman microspectroscopy, we verified in situ the interaction of amino-modified ZrO2 NP with cultivated macrophages. The results demonstrated strong adhesion properties of the NP to the cell membrane and internalization into the cells. The intracellular localization of the NP was visualized via Raman depth scans of single cells. After the cells were treated with sodium azide (NaN3) and 2-deoxy-glucose to inhibit the phagocytic activity, NP were still detected inside cells to comparable percentages. The observed tendency of amino-modified ZrO2 NP to interact with the cultivated macrophages may influence membrane integrity and cellular functions of alveolar macrophages in the respiratory system.

Graphical abstract

Detection of ZrO2 NM at subcellular level

Keywords

Raman microspectroscopy ZrO2 nanoparticles Surface functionalization Cellular uptake 

Notes

Acknowledgments

The authors gratefully acknowledge the financial support from BMBF in the project nanoGEM (FKZ 03X0105A).

Compliance with ethical standards

Conflicts of interest

We certify that there is no conflict of interest with any financial or non-financial organization regarding the material discussed in the manuscript.

Supplementary material

216_2016_9710_MOESM1_ESM.pdf (229 kb)
ESM 1 (PDF 229 kb)

References

  1. 1.
    Ruge CA, Driessen M, Haase A, Schäfer UF, Luch A, Lehr C-M. Analyzing the Biological Entity of Nanomaterials: Characterization of Nanomaterial Properties in Biological Matrices. Safety of Nanomaterials along Their Lifecycle: CRC Press; 2014. p. 59–96.Google Scholar
  2. 2.
    Landsiedel R, Sauer UG, Ma-Hock L, Schnekenburger J, Wiemann M. Pulmonary toxicity of nanomaterials: a critical comparison of published in vitro assays and in vivo inhalation or instillation studies. Nanomedicine. 2014;9(16):2557–85.CrossRefGoogle Scholar
  3. 3.
    Walkey CD, Chan WCW. Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment. Chem Soc Rev. 2012;41(7):2780–99.CrossRefGoogle Scholar
  4. 4.
    Fröhlich E. The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomedicine. 2012;7:5577–91.CrossRefGoogle Scholar
  5. 5.
    Buesen R, Landsiedel R, Sauer UG, Wohlleben W, Groeters S, Strauss V, et al. Effects of SiO(2), ZrO(2), and BaSO(4) nanomaterials with or without surface functionalization upon 28-day oral exposure to rats. Arch Toxicol. 2014;88(10):1881–906.CrossRefGoogle Scholar
  6. 6.
    Landsiedel R, Ma-Hock L, Hofmann T, Wiemann M, Strauss V, Treumann S, et al. Application of short-term inhalation studies to assess the inhalation toxicity of nanomaterials. Part Fibre Toxicol. 2014;11:16.CrossRefGoogle Scholar
  7. 7.
    Marzaioli V, Aguilar-Pimentel JA, Weichenmeier I, Luxenhofer G, Wiemann M, Landsiedel R, et al. Surface modifications of silica nanoparticles are crucial for their inert versus proinflammatory and immunomodulatory properties. Int J Nanomedicine. 2014;9:2815–32.Google Scholar
  8. 8.
    Silge A, Bräutigam K, Bocklitz T, Rösch P, et al. ZrO2 nanoparticles labeled via a native protein corona: detection by fluorescence microscopy and Raman microspectroscopy in rat lungs. Analyst. 2015;140(15):5120–8.CrossRefGoogle Scholar
  9. 9.
    Allen L-AH, Aderem A. Mechanisms of phagocytosis. Curr Opin Immunol. 1996;8(1):36–40.CrossRefGoogle Scholar
  10. 10.
    Mu Q, Jiang G, Chen L, Zhou H, Fourches D, Tropsha A, et al. Chemical basis of interactions between engineered nanoparticles and biological systems. Chem Rev. 2014;114(15):7740–81.CrossRefGoogle Scholar
  11. 11.
    Kuhlbusch TAJ. nanoGEM Abschlussbericht. Hannover: Technische Informationsbibliothek (TIB); 2013. 235 p.Google Scholar
  12. 12.
    Wohlleben W, Driessen MD, Raesch S, Schaefer UF, Schulze C, Vacano BV, et al. Influence of agglomeration and specific lung lining lipid/protein interaction on short-term inhalation toxicity. Nanotoxicology. 2016:1–11.Google Scholar
  13. 13.
    Kroll A, Pillukat MH, Hahn D, Schnekenburger J. Interference of engineered nanoparticles with in vitro toxicity assays. Arch Toxicol. 2012;86(7):1123–36.CrossRefGoogle Scholar
  14. 14.
    Bonifacio A, Beleites C, Vittur F, Marsich E, Semeraro S, Paoletti S, et al. Chemical imaging of articular cartilage sections with Raman mapping, employing uni- and multi-variate methods for data analysis. Analyst. 2010;135(12):3193–204.CrossRefGoogle Scholar
  15. 15.
    Bräutigam K, Bocklitz T, Schmitt M, Rösch P, Popp J. Raman spectroscopic imaging for the real-time detection of chemical changes associated with docetaxel exposure. ChemPhysChem. 2013;14(3):550–3.CrossRefGoogle Scholar
  16. 16.
    Bräutigam K, Bocklitz T, Silge A, Dierker C, Ossig R, Schnekenburger J, et al. Comparative two- and three-dimensional analysis of nanoparticle localization in different cell types by Raman spectroscopic imaging. J Mol Struct. 2014;1073:44–50.CrossRefGoogle Scholar
  17. 17.
    Diem M, Romeo M, Boydston-White S, Miljkovic M, Matthäus C. A decade of vibrational micro-spectroscopy of human cells and tissue (1994–2004). Analyst. 2004;129(10):880–5.CrossRefGoogle Scholar
  18. 18.
    Hartmann K, Becker-Putsche M, Bocklitz T, Pachmann K, Niendorf A, Rösch P, et al. A study of Docetaxel-induced effects in MCF-7 cells by means of Raman microspectroscopy. Anal Bioanal Chem. 2012;403(3):745–53.CrossRefGoogle Scholar
  19. 19.
    Krafft C, Knetschke T, Funk RHW, Salzer R. Identification of organelles and vesicles in single cells by Raman microspectroscopic mapping. Vib Spectrosc. 2005;38(1–2):85–93.CrossRefGoogle Scholar
  20. 20.
    Bocklitz TW, Guo S, Ryabchykov O, Vogler N, Popp J. Raman Based Molecular Imaging and Analytics: A Magic Bullet for Biomedical Applications!? Anal Chem. 2015.Google Scholar
  21. 21.
    Silge A, Abdou E, Schneider K, Meisel S, Bocklitz T, Lu-Walther H-W, et al. Shedding light on host niches: label-free in situ detection of Mycobacterium gordonae via carotenoids in macrophages by Raman microspectroscopy. Cell Microbiol. 2015;17(6):832–42.CrossRefGoogle Scholar
  22. 22.
    Izak-Nau E, Voetz M. As-produced: intrinsic physico-chemical properties and appropriate characterization tools. Safety of Nanomaterials along Their Lifecycle 2014. p. 3–24.Google Scholar
  23. 23.
    R Development Core Team. R: A language and environment for statistical computing. . R Foundation for Statistical Computing; 2010.Google Scholar
  24. 24.
    Bocklitz T, Walter A, Hartmann K, Rösch P, Popp J. How to pre-process Raman spectra for reliable and stable models? Anal Chim Acta. 2011;704(1–2):47–56.CrossRefGoogle Scholar
  25. 25.
    De Gelder J, De Gussem K, Vandenabeele P, Moens L. Reference database of Raman spectra of biological molecules. J Raman Spectrosc. 2007;38(9):1133–47.CrossRefGoogle Scholar
  26. 26.
    Movasaghi Z, Rehman S, Rehman IU. Raman spectroscopy of biological tissues. Appl Spectrosc Rev. 2007;42(5):493–541.CrossRefGoogle Scholar
  27. 27.
    Bouvier P, Lucazeau G. Raman spectra and vibrational analysis of nanometric tetragonal zirconia under high pressure. J Phys Chem Solids. 2000;61(4):569–78.CrossRefGoogle Scholar
  28. 28.
    Kock LD, Lekgoathi MDS, Snyders E, Wagener JB, Nel JT, Havenga JL. The determination of percentage dissociation of zircon (ZrSiO4) to plasma-dissociated zircon (ZrO2.SiO2) by Raman spectroscopy. J Raman Spectrosc. 2012;43(6):769–73.CrossRefGoogle Scholar
  29. 29.
    Tabares JAM, Anglada MJ. Quantitative analysis of monoclinic phase in 3Y-TZP by Raman spectroscopy. J Am Ceram Soc. 2010;93(6):1790–5.Google Scholar
  30. 30.
    Zhao N, Pan D, Nie W, Ji X. Two-phase synthesis of shape-controlled colloidal zirconia nanocrystals and their characterization. J Am Chem Soc. 2006;128(31):10118–24.CrossRefGoogle Scholar
  31. 31.
    Bonifacio A, Finaurini S, Krafft C, Parapini S, Taramelli D, Sergo V. Spatial distribution of heme species in erythrocytes infected with Plasmodium falciparum by use of resonance Raman imaging and multivariate analysis. Anal Bioanal Chem. 2008;392(7–8):1277–82.CrossRefGoogle Scholar
  32. 32.
    Bruce Alberts AJ, Julian Lewis, Martin Raff, Keith Roberts, Peter Walter. Chapter 13 Intracellular Vesicular Traffic. Molecular Biology of the Cell. New York: Garland Science; 2007.Google Scholar
  33. 33.
    Monopoli MP, Aberg C, Salvati A, Dawson KA. Biomolecular coronas provide the biological identity of nanosized materials. Nat Nanotechnol. 2012;7(12):779–86.CrossRefGoogle Scholar
  34. 34.
    Monopoli MP, Walczyk D, Campbell A, Elia G, Lynch I, Bombelli FB, et al. Physical-chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles. J Am Chem Soc. 2011;133(8):2525–34.CrossRefGoogle Scholar
  35. 35.
    Treuel L, Docter D, Maskos M, Stauber RH. Protein corona—from molecular adsorption to physiological complexity. Beilstein J Nanotechnol. 2015;6:857–73.CrossRefGoogle Scholar
  36. 36.
    Treuel L, Eslahian KA, Docter D, Lang T, Zellner R, Nienhaus K, et al. Physicochemical characterization of nanoparticles and their behavior in the biological environment. Phys Chem Chem Phys. 2014;16(29):15053–67.CrossRefGoogle Scholar
  37. 37.
    Kou L, Sun J, Zhai Y, He Z. The endocytosis and intracellular fate of nanomedicines: implication for rational design. Asian J Pharm Sci. 2013;8(1):1–10.CrossRefGoogle Scholar
  38. 38.
    Venter G, Oerlemans F, Wijers M, Willemse M, Fransen JAM, Wieringa B. Glucose controls morphodynamics of LPS-stimulated macrophages. Plos ONE. 2014;9(5):15.Google Scholar
  39. 39.
    Treuel L, Jiang XE, Nienhaus GU. New views on cellular uptake and trafficking of manufactured nanoparticles. Journal of the Royal Society Interface. 2013;10(82).Google Scholar
  40. 40.
    Wendel Wohlleben TAJK, Jürgen Schnekenburger, and Claus-Michael Lehr. Safety of nanomaterials along their lifecycle release, exposure, and human hazards: CRC Press; 2014.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Anja Silge
    • 1
    • 2
  • Thomas Bocklitz
    • 1
    • 2
  • Rainer Ossig
    • 3
  • Jürgen Schnekenburger
    • 3
  • Petra Rösch
    • 1
    • 2
  • Jürgen Popp
    • 1
    • 2
    • 4
  1. 1.Institute of Physical Chemistry and Abbe Center of PhotonicsFriedrich-Schiller-Universität JenaJenaGermany
  2. 2.InfectoGnostics Research Campus Jena, Center for Applied ResearchJenaGermany
  3. 3.Biomedical Technology CenterWestfälische Wilhelms-Universität MünsterMünsterGermany
  4. 4.Leibniz Institute of Photonic TechnologyJenaGermany

Personalised recommendations