Skip to main content
Log in

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

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

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.

Detection of ZrO2 NM at subcellular level

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  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.

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  4. Fröhlich E. The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomedicine. 2012;7:5577–91.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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. 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.

    Article  CAS  Google Scholar 

  9. Allen L-AH, Aderem A. Mechanisms of phagocytosis. Curr Opin Immunol. 1996;8(1):36–40.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  11. Kuhlbusch TAJ. nanoGEM Abschlussbericht. Hannover: Technische Informationsbibliothek (TIB); 2013. 235 p.

  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.

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

  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.

    Article  CAS  Google Scholar 

  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.

  23. R Development Core Team. R: A language and environment for statistical computing. . R Foundation for Statistical Computing; 2010.

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  26. Movasaghi Z, Rehman S, Rehman IU. Raman spectroscopy of biological tissues. Appl Spectrosc Rev. 2007;42(5):493–541.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  35. Treuel L, Docter D, Maskos M, Stauber RH. Protein corona—from molecular adsorption to physiological complexity. Beilstein J Nanotechnol. 2015;6:857–73.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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. 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).

  40. Wendel Wohlleben TAJK, Jürgen Schnekenburger, and Claus-Michael Lehr. Safety of nanomaterials along their lifecycle release, exposure, and human hazards: CRC Press; 2014.

Download references

Acknowledgments

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

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jürgen Popp.

Ethics declarations

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.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 229 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Silge, A., Bocklitz, T., Ossig, R. et al. The interaction of an amino-modified ZrO2 nanomaterial with macrophages—an in situ investigation by Raman microspectroscopy. Anal Bioanal Chem 408, 5935–5943 (2016). https://doi.org/10.1007/s00216-016-9710-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-016-9710-x

Keywords

Navigation