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Probing the Cytotoxicity of Nanoparticles: Experimental Pitfalls and Artifacts

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Measuring Biological Impacts of Nanomaterials

Part of the book series: Bioanalytical Reviews ((BIOREV,volume 5))

Abstract

Throughout the last years, a huge variety of different nanoparticle formulations have been studied with the aim to assess their harmlessness in biological systems, to elucidate how the morphological features govern their impact on cells, and to develop cell labeling strategies for biomedical purposes. Most of such studies are based on the use of various cell viability assays. Interestingly, different results – even contradictory ones – have been observed between the groups, even though the respective nanoparticle formulations were more or less similar. One possible reason for such discrepancies is the occurrence of specific interactions between the nanoparticles and the ingredients of the respective cell viability assays. A similar situation can be encountered when researchers investigate the labeling of (stem) cells for biomedical purposes. Hereto, different labeling efficiencies were observed with the corresponding effects on cell viability and functionality. Therefore, the present review focuses on potential pitfalls and artifacts associated with the cytotoxicity evaluation of nanomaterials.

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References

  1. Tenzer S et al (2011) Nanoparticle size is a critical physicochemical determinant of the human blood plasma corona: a comprehensive quantitative proteomic analysis. ACS Nano 5(9):7155–7167

    Article  CAS  Google Scholar 

  2. Gratton SEA et al (2008) The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci U S A 105(33):11613–11618

    Article  CAS  Google Scholar 

  3. Chithrani BD, Ghazani AA, Chan WCW (2006) Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 6(4):662–668

    Article  CAS  Google Scholar 

  4. Wang J et al (2010) The complex role of multivalency in nanoparticles targeting the transferrin receptor for cancer therapies. J Am Chem Soc 132(32):11306–11313

    Article  CAS  Google Scholar 

  5. Decker T, Lohmann-Matthes ML (1988) A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods 115(1):61–69

    Article  CAS  Google Scholar 

  6. Buttke TM, McCubrey JA, Owen TC (1993) Use of an aqueous soluble tetrazolium formazan assay to measure viability and proliferation of lymphokine-dependent cell-lines. J Immunol Methods 157(1–2):233–240

    Article  CAS  Google Scholar 

  7. Hong SC et al (2011) Subtle cytotoxicity and genotoxicity differences in superparamagnetic iron oxide nanoparticles coated with various functional groups. Int J Nanomedicine 6:3219–3231

    CAS  Google Scholar 

  8. Hoskins C et al (2012) Dilemmas in the reliable estimation of the in-vitro cell viability in magnetic nanoparticle engineering: which tests and what protocols? Nanoscale Res Lett 7:1–12

    Article  Google Scholar 

  9. Wang PW, Henning SM, Heber D (2010) Limitations of MTT and MTS-based assays for measurement of antiproliferative activity of green tea polyphenols. PLoS One 5(4)

    Google Scholar 

  10. Monteiro-Riviere NA, Inman AO, Zhang LW (2009) Limitations and relative utility of screening assays to assess engineered nanoparticle toxicity in a human cell line. Toxicol Appl Pharmacol 234(2):222–235

    Article  CAS  Google Scholar 

  11. Fisichella M et al (2009) Mesoporous silica nanoparticles enhance MTT formazan exocytosis in HeLa cells and astrocytes. Toxicol In Vitro 23(4):697–703

    Article  CAS  Google Scholar 

  12. Belyanskaya L et al (2007) The reliability and limits of the MTT reduction assay for carbon nanotubes-cell interaction. Carbon 45(13):2643–2648

    Article  CAS  Google Scholar 

  13. Worle-Knirsch JM, Pulskamp K, Krug HF (2006) Oops they did it again! Carbon nanotubes hoax scientists in viability assays. Nano Lett 6(6):1261–1268

    Article  CAS  Google Scholar 

  14. Cheng C et al (2009) Toxicity and imaging of multi-walled carbon nanotubes in human macrophage cells. Biomaterials 30(25):4152–4160

    Article  CAS  Google Scholar 

  15. Monteiro-Riviere NA, Inman AO (2006) Challenges for assessing carbon nanomaterial toxicity to the skin. Carbon 44(6):1070–1078

    Article  CAS  Google Scholar 

  16. Gao LZ et al (2007) Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. Nat Nanotechnol 2(9):577–583

    Article  CAS  Google Scholar 

  17. Conner S, Schmid S (2003) Regulated portals of entry into the cell. Nature 422:37–44

    Article  CAS  Google Scholar 

  18. Neoh KG, Kang ET (2012) Surface modification of magnetic nanoparticles for stem cell labeling. Roy Soc Chem 8:2057–2069

    CAS  Google Scholar 

  19. Berman SM, Walczak P, Bulte JWM (2011) Tracking stem cells using magnetic nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol 3(4):343–355

    Article  CAS  Google Scholar 

  20. Ittrich H et al (2007) In vivo magnetic resonance imaging of iron oxide-labeled, arterially injected mesenchymal stem cells in kidneys of rats with acute ischemic kidney injury: detection and monitoring at 3T. J Magn Reson Imaging 25(6):1179–1191

    Article  Google Scholar 

  21. Daldrup-Link HE et al (2005) Hematopoietic progenitor cells from umbilical cord blood and from peripheral blood for subsequent in vivo tracking in a xenotransplant mouse model XXX. Acad Radiol 12(4):502–510

    Article  Google Scholar 

  22. Sun R et al (2005) Physical and biological characterization of superparamagnetic iron oxide- and ultrasmall superparamagnetic iron oxide-labeled cells – a comparison. Invest Radiol 40(8):504–513

    Article  Google Scholar 

  23. Ma YJ, Gu HC (2007) Study on the endocytosis and the internalization mechanism of aminosilane-coated Fe3O4 nanoparticles in vitro. J Mater Sci Mater Med 18(11):2145–2149

    Article  CAS  Google Scholar 

  24. Kettering M et al (2007) Magnetic nanoparticles as bimodal tools in magnetically induced labelling and magnetic heating of tumour cells: an in vitro study. Nanotechnology 18:175101

    Article  Google Scholar 

  25. Jordan A et al (1999) Endocytosis of dextran and silan-coated magnetite nanoparticles and the effect of intracellular hyperthermia on human mammary carcinoma cells in vitro. J Magn Magn Mater 194(1–3):185–196

    Article  CAS  Google Scholar 

  26. Daldrup-Link HE et al (2003) Targeting of hematopoietic progenitor cells with MR contrast agents. Radiology 228(3):760–767

    Article  Google Scholar 

  27. Pinkernelle J et al (2005) Imaging of single human carcinoma cells in vitro using a clinical whole-body magnetic resonance scanner at 3.0T. Magn Reson Med 53(5):1187–1192

    Article  CAS  Google Scholar 

  28. Seidl J, Knuechel R, Kunz-Schughart LA (1999) Evaluation of membrane physiology following fluorescence activated or magnetic cell separation. Cytometry 36(2):102–111

    Article  CAS  Google Scholar 

  29. Kostura L et al (2004) Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis. NMR Biomed 17(7):513–517

    Article  Google Scholar 

  30. Bult JWM et al (2004) Chondrogenic differentiation of mesenchymal stem cells is inhibited after magnetic labeling with ferumoxides. Blood 104(10):3410–3412

    Article  Google Scholar 

  31. Schafer R et al (2009) Labeling of human mesenchymal stromal cells with superparamagnetic iron oxide leads to a decrease in migration capacity and colony formation ability. Cytotherapy 11(1):68–78

    Article  Google Scholar 

  32. Chen YC et al (2010) The inhibitory effect of superparamagnetic iron oxide nanoparticle (Ferucarbotran) on osteogenic differentiation and its signaling mechanism in human mesenchymal stem cells. Toxicol Appl Pharmacol 245(2):272–279

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the German Research Foundation (DFG) under the contract number HI 698/7-2, HI 698/8-2, and HI 698/11-2 and the Federal Ministry of Education and Research (BMBF, Project “NanoMed”). The own data on potential cell viability assay artifacts are based on nanoparticles synthesized by Chemicell, Berlin, Germany, Dr. Rudolf Herrmann, University of Augsburg, Germany, Oskar Köhler (M.S.) University of Mainz, Germany, and Isabel Schick (M.S.), University of Mainz, Germany. We gratefully acknowledge valuable contribution of Susann Burgold and Julia Göring.

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Correspondence to Ingrid Hilger .

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© 2013 Springer International Publishing Switzerland

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Domey, J., Haslauer, L., Grau, I., Strobel, C., Kettering, M., Hilger, I. (2013). Probing the Cytotoxicity of Nanoparticles: Experimental Pitfalls and Artifacts. In: Wegener, J. (eds) Measuring Biological Impacts of Nanomaterials. Bioanalytical Reviews, vol 5. Springer, Cham. https://doi.org/10.1007/11663_2013_8

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