Skip to main content
SpringerLink
Log in

Detection of organic nanoparticles in human bone marrow-derived stromal cells using ToF–SIMS and PCA

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

Abstract

The detection and localization of polymer-based nanoparticles in human bone marrow-derived stromal cells (hBMSC) by time-of-flight secondary ion mass spectrometry (ToF–SIMS) is reported as an example for the mass spectrometry imaging of organic nanoparticles in cell environments. Polyelectrolyte complex (PEC) nanoparticles (NP) made of polyethylenimine (PEI) and cellulose sulfate (CS), which were developed as potential drug carrier and coatings for implant materials, were chosen for the imaging experiments. To investigate whether the PEI/CS–NP were taken up by the hBMSC ToF–SIMS measurements on cross sections of the cells and depth profiling of whole, single cells were carried out. Since the mass spectra of the PEI/CS nanoparticles are close to the mass spectra of the cells principal component analysis (PCA) was performed to get specific masses of the PEI/CS–NP. Mass fragments originating from the NP compounds especially from cellulose sulfate could be used to unequivocally detect and image the PEI/CS–NP inside the hBMSC. The findings were confirmed by light and transmission electron microscopy.

During ToF-SIMS analysis Bi3 + primary ions hit the sample surface and so called secondary ions (SI) are emitted and detected in the mass analyser. Exemplary mass images of cross sections of human mesenchymal stromal cells (red; m/z = 86.1 u) cultured with organic nanoparticles (green; m/z = 143.0 u) were obtained

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

Access this article

Log in via an institution

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
Fig. 6

Similar content being viewed by others

References

  1. Duncan R (2003) The dawning era of polymer therapeutics. Nat Rev Drug Discov 2(5):347–360

    CAS  Google Scholar 

  2. Müller M (2014) Sizing, Shaping and Pharmaceutical Applications of Polyelectrolyte Complex Nanoparticles. In: Müller M (ed) Polyelectrolyte complexes in the dispersed and solid state II, vol 256, Advances in Polymer Science. Springer, Berlin, pp pp 197–pp 260. doi:10.1007/12_2012_170

    Chapter  Google Scholar 

  3. Yang L, Webster TJ (2009) Nanotechnology controlled drug delivery for treating bone diseases. Expert Opin Drug Deliv 6(8):851–864. doi:10.1517/17425240903044935

    CAS  Google Scholar 

  4. Müller M, Keßler B (2012) Release of pamidronate from poly(ethyleneimine)/cellulose sulphate complex nanoparticle films: An in situ ATR-FTIR study. J Pharm Biomed Anal 66(0):183–190. doi:10.1016/j.jpba.2012.03.047

    Google Scholar 

  5. Russell RG (2011) Bisphosphonates: the first 40 years. Bone 49(1):2–19. doi:10.1016/j.bone.2011.04.022

    Article  CAS  Google Scholar 

  6. Torger B, Vehlow D, Urban B, Salem S, Appelhans D, Muller M (2013) Cast adhesive polyelectrolyte complex particle films of unmodified or maltose-modified poly(ethyleneimine) and cellulose sulphate: fabrication, film stability and retarded release of zoledronate. Biointerphases 8(1):25

    Article  Google Scholar 

  7. Woltmann B, Torger B, Müller M, Hempel U (2014) Interaction between immobilized polyelectrolyte complex nanoparticles and human mesenchymal stromal cells. Int J Nanomedicine 9:2205–2215. doi:10.2147/IJN.S61198

    Google Scholar 

  8. Nienhaus GU, Nienhaus K (2013) Fluorescence labeling. in: fluorescence microscopy. Wiley, pp 143–173. doi:10.1002/9783527671595.ch4

  9. Muhlfeld C, Rothen-Rutishauser B, Vanhecke D, Blank F, Gehr P, Ochs M (2007) Visualization and quantitative analysis of nanoparticles in the respiratory tract by transmission electron microscopy. Part Fibre Toxicol 4(1):11

    Google Scholar 

  10. Vickerman JC, Briggs D (2013) ToF-SIMS: materials analysis by mass spectrometry-2nd edition. IM

  11. Malmberg P, Kriegeskotte C, Arlinghaus HF, Hagenhoff B, Homlgren J, Nilsson M, Nygren H (2008) Depth profiling of cells and tissue by using C + 60 and SF5+ as sputter ions. Appl Surf Sci 255:926–928

    CAS  Google Scholar 

  12. Nygren H, Hagenhoff B, Malmberg P, Nilsson M, Richter K (2007) Bioimaging TOF-SIMS: high resolution 3D imaging of single cells. Microsc Res Tech 70(11):969–974

    CAS  Google Scholar 

  13. Brison J, Benoit DSW, Muramoto S, Robinson M, Stayton PS, Castner DG (2011) ToF-SIMS imaging and depth profiling of HeLa cells treated with bromodeoxyuridine. Surf Interface Anal 43(1–2):354–357. doi:10.1002/sia.3415

    CAS  Google Scholar 

  14. Kokesch-Himmelreich J, Schumacher M, Rohnke M, Gelinsky M, Janek J (2013) ToF-SIMS analysis of osteoblast-like cells and their mineralized extracellular matrix on strontium enriched bone cements. Biointerphases 8(1):17

    Article  Google Scholar 

  15. Hagenhoff B, Breitenstein D, Tallarek E, Möllers R, Niehuis E, Sperber M, Goricnik B, Wegener J (2013) Detection of micro- and nano-particles in animal cells by ToF-SIMS 3D analysis. Surf Interface Anal 45(1):315–319. doi:10.1002/sia.5141

    CAS  Google Scholar 

  16. Haase A, Arlinghaus H, Tentschert J, Jungnickel H, Graf P, Mantion A, Draude F, Galla S, Plendl J, Goetz ME, Masic A, Meier W, Thünemann AF, Taubert A, Luch A (2011) Application of laser postionization secondary neutral mass spectrometry/ time-of-flight secondary ion mass spectrometry in nanotoxicology: visualization of nanosilver in human macrophages and cellular responses. ACS Nano 5(4):3059–3068

    Article  CAS  Google Scholar 

  17. Pauksch L, Hartmann S, Rohnke M, Szalay G, Alt V, Schnettler R, Lips KS (2014) Biocompatibility of silver nanoparticles and silver ions in primary human mesenchymal stem cells and osteoblasts. Acta Biomater 10(1):439–449. doi:10.1016/j.actbio.2013.09.037

    CAS  Google Scholar 

  18. Graham D, Castner D (2012) Multivariate analysis of ToF-SIMS data from multicomponent systems: the why, when, and how. Biointerphases 7(1):1–12. doi:10.1007/s13758-012-0049-3

    Article  Google Scholar 

  19. Kulp KS, Berman ESF, Knize MG, Shattuck DL, Nelson EJ, Wu L, Montgomery JL, Felton JS, Wu KJ (2006) Chemical and biological differentiation of three human breast cancer cell types using time-of-flight secondary ion mass spectrometry. Anal Chem 78(11):3651–3658. doi:10.1021/ac060054c

    CAS  Google Scholar 

  20. Wu L, Lu X, Kulp K, Knize M, Berman E, Nelson E, Felton J, Wu K (2007) Imaging and differentiation of mouse embryo tissues by ToF-SIMS. Int J Mass Spectrom 260(2–3):137–145. doi:10.1016/j.ijms.2006.09.029

    CAS  Google Scholar 

  21. Bernsmann F, Richert L, Senger B, Lavalle P, Voegel J-C, Schaaf P, Ball V (2008) Use of dopamine polymerisation to produce free-standing membranes from (PLL-HA)n exponentially growing multilayer films. Soft Matter 4(8):1621–1624. doi:10.1039/b806649c

    Article  CAS  Google Scholar 

  22. Oswald J, Boxberger S, Jørgensen B, Feldmann S, Ehninger G, Bornhäuser M, Werner C (2004) Mesenchymal stem cells Can Be differentiated into endothelial cells in vitro. Stem Cells 22(3):377–384. doi:10.1634/stemcells.22-3-377

    Article  Google Scholar 

  23. Wold S, Esbensen K, Geladi P (1987) Principal component analysis. Chemom Intell Lab Syst 2(1–3):37–52. doi:10.1016/0169-7439(87)80084-9

    CAS  Google Scholar 

  24. Geladi P, Isaksson H, Lindqvist L, Wold S, Esbensen K (1989) Principal component analysis of multivariate images. Chemom Intell Lab Syst 5(3):209–220. doi:10.1016/0169-7439(89)80049-8

    Google Scholar 

  25. Brandenberger C, Clift M, 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(1):15

    Google Scholar 

  26. Fletcher JS, Rabbani S, Henderson A, Lockyer NP, Vickerman JC (2010) Three-dimensional mass spectral imaging of HeLa-M cells-sample preparation, data interpretation and visualisation. Rapid Commun Mass Spectrom 25:925

    Google Scholar 

  27. Wagner MS, Castner DG (2001) Characterization of adsorbed protein films by time-of-flight secondary ion mass spectrometry with principal component analysis. Langmuir 17(15):4649–4660. doi:10.1021/la001209t

    Article  CAS  Google Scholar 

  28. Fletcher JS, Lockyer NP, Vickerman JC (2009) Molecular SIMS imaging; spatial resolution and molecular sensitivity: have we reached the end of the road? Is there light at the end of the tunnel? 43:253

  29. Sridharan G, Shankar A (2012) Toluidine blue: a review of its chemistry and clinical utility. J Oral Maxillofac Pathol 16(2):251–255. doi:10.4103/0973-029x.99081

    Google Scholar 

  30. Rabbani S, Barber AM, Fletcher JS, Lockyer NP, Vickerman JC (2011) TOF-SIMS with argon gas cluster ion beams: a comparison with C60+. Anal Chem 83(10):3793–3800. doi:10.1021/ac200288v

    CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Sigrid Kettner (work group Prof. Arnhold, Justus-Liebig-University of Giessen) for preparing the cross sections of the cell samples for TEM and ToF–SIMS analysis. We also would like to thank Dr. Anja Walther and Silke Tulok (CFCI Core Facility Cellular “Imaging”, MTZ Imaging Facility, Dresden University of Technology) for their support with the cLSM. We thank Dr. Anja Henss for all the helpfull discussions and Dan Graham, Ph.D., for developing the NESAC/BIO Toolbox used in this study and NIH grant EB-002027 for supporting the toolbox development. This study was funded by the Deutsche Forschungsgemeinschaft (DFG) as part of the Collaborative Research Centre Transregio 79 (SFB/TRR 79–subproject M5, in collaboration with M7 and B4).

Author information

Authors and Affiliations

  1. Institute of Physical Chemistry, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 58, 35392, Giessen, Germany

    Julia Kokesch-Himmelreich, Marcus Rohnke & Jürgen Janek

  2. Institute of Physiological Chemistry, Faculty of Medicine, Dresden University of Technology, Fiedlerstrasse 42, 01307, Dresden, Germany

    Beatrice Woltmann & Ute Hempel

  3. Department of Polyelectrolytes and Dispersions, Leibniz Institute of Polymer Research, Hohe Strasse 6, 01069, Dresden, Germany

    Bernhard Torger & Martin Müller

  4. Department of Chemistry and Food Chemistry, Dresden University of Technology, Helmholtzstrasse 10, 01069, Dresden, Germany

    Bernhard Torger & Martin Müller

  5. Institute of Veterinary Anatomy, -Histology, -Embryology, Justus-Liebig-University of Giessen, Frankfurter Strasse 98, 35392, Giessen, Germany

    Stefan Arnhold

Authors
  1. Julia Kokesch-Himmelreich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Beatrice Woltmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernhard Torger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marcus Rohnke
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stefan Arnhold
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ute Hempel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Martin Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jürgen Janek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marcus Rohnke.

Additional information

Published in the topical collection Mass Spectrometry Imaging with guest editors Andreas Römpp and Uwe Karst.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 2.13 MB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kokesch-Himmelreich, J., Woltmann, B., Torger, B. et al. Detection of organic nanoparticles in human bone marrow-derived stromal cells using ToF–SIMS and PCA. Anal Bioanal Chem 407, 4555–4565 (2015). https://doi.org/10.1007/s00216-015-8647-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-015-8647-9

Keywords

Search

Navigation