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Imaging nanoparticles in cells by nanomechanical holography

Nature Nanotechnology volume 3, pages 501–505 (2008)Cite this article

Abstract

Nanomaterials have potential medical applications, for example in the area of drug delivery, and their possible adverse effects and cytotoxicity are curently receiving attention1,2. Inhalation of nanoparticles is of great concern, because nanoparticles can be easily aerosolized. Imaging techniques that can visualize local populations of nanoparticles at nanometre resolution within the structures of cells are therefore important3. Here we show that cells obtained from mice exposed to single-walled carbon nanohorns can be probed using a scanning probe microscopy technique called scanning near field ultrasonic holography. The nanohorns were observed inside the cells, and this was further confirmed using micro Raman spectroscopy. Scanning near field ultrasonic holography is a useful technique for probing the interactions of engineered nanomaterials in biological systems, which will greatly benefit areas in drug delivery and nanotoxicology.

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Figure 1: Intracellular imaging of aspirated nanoparticles using ultrasonic holography.
Figure 2: Presence of SWCNHs inside cells obtained from mice lungs.
Figure 3: Nanoparticles detected inside red blood cells.
Figure 4: High-resolution images of nanoparticles in red blood cells.
Figure 5: Confirming the presence of SWCNHs inside cells using Raman spectroscopy.

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References

  1. Nel, A., Xia, T., Madler, L. & Li, N. Toxic potential of materials at the nanolevel. Science 311, 622–627 (2006).

    Article  CAS  Google Scholar 

  2. Panessa-Warren, B. J., Warren, J. B., Wong, S. S. & Misewich, J. A. Biological cellular response to carbon nanoparticle toxicity. J. Phys. Condens. Matter 18, S2185–S2201 (2006).

    Article  CAS  Google Scholar 

  3. Stone, V. & Donaldson, K. Signs of stress. Nature Nanotech. 1, 23–24 (2006).

    Article  CAS  Google Scholar 

  4. Colvin, V. L. The potential environmental impact of engineered nanomaterials. Nature Biotechnol. 21, 1166–1170 (2003).

    Article  CAS  Google Scholar 

  5. Borm, P. et al. The potential risks of nanomaterials : a review carried out for ECETOC. Part. Fibre Toxicol. 3, 11–46 (2006).

    Article  Google Scholar 

  6. Xia, T. et al. Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Lett. 6, 1794–1807 (2006).

    Article  CAS  Google Scholar 

  7. Oberdörster, G., Oberdörster, E. & Oberdörster, J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect. 113, 823–839 (2005).

    Article  Google Scholar 

  8. Holsapple, M. P. et al. Research strategies for safety evaluation of nanomaterials, Part II : Toxicological and safety evaluation of nanomaterials, current challenges and data needs. Toxicol. Sci. 88, 12–17 (2005).

    Article  CAS  Google Scholar 

  9. Geiser, M. et al. Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells. Environ. Health Perspect. 113, 1555–1560 (2005).

    Article  Google Scholar 

  10. Wörle-Knirsch, J. M., Pulskamp, K. & Krug, H. F. Oops they did it again! Carbon nanotubes hoax scientists in viability assays. Nano Lett. 6, 1261–1268 (2006).

    Article  Google Scholar 

  11. Porter, A. E. et al. Direct imaging of single-walled carbon nanotubes in cells. Nature Nanotech. 2, 713–717 (2007).

    Article  CAS  Google Scholar 

  12. Rabe, U. & Arnold, W. Acoustic microscopy by atomic force microscopy. Appl. Phys. Lett. 64, 1493–1495 (1994).

    Article  Google Scholar 

  13. Kolosov, O. V. et al. Imaging the elastic nanostructure of Ge islands by ultrasonic force microscopy. Phys. Rev. Lett. 81, 1046–1049 (1998).

    Article  CAS  Google Scholar 

  14. Martinez, N. F., Patil, S., Lozano, J. R. & Garcia, R. Enhanced compositional sensitivity in atomic force microscopy by the excitation of the first two flexural modes. Appl. Phys. Lett. 89, 153115 (2006).

    Article  Google Scholar 

  15. Sahin, O. et al. An atomic force microscope tip designed to measure time-varying nanomechanical forces. Nature Nanotech. 2, 507–514 (2007).

    Article  Google Scholar 

  16. Garcia, R., Margerle, R. & Perez, R. Nanoscale compositional mapping with gentle forces. Nature Mater. 6, 405–411 (2007).

    Article  CAS  Google Scholar 

  17. Shekhawat, G. S. & Dravid, V. P. Nanoscale imaging of buried structures via scanning near-field ultrasound holography. Science 310, 89–92 (2005).

    Article  CAS  Google Scholar 

  18. Cantrell, S. A., Cantrell, J. H. & Lillehei, P. T. Nanoscale subsurface imaging via resonant different-frequency atomic force ultrasonic microscopy. J. Appl. Phys. 101, 114324 (2007).

    Article  Google Scholar 

  19. Kreyling, W. G., Semmler-Behnke, M. & Moller, W. Health implications of nanoparticles. J. Nanopart. Res. 8, 543–562 (2006).

    Article  CAS  Google Scholar 

  20. Iijima, S. et al. Nano-aggregates of single-walled graphitic carbon nano-horns. Chem. Phys. Lett. 309, 165–170 (1999).

    Article  CAS  Google Scholar 

  21. Tuinstra, F. & Koenig, J. L. Raman spectrum of graphite. J. Chem. Phys. 53, 1126–1130 (1970).

    Article  CAS  Google Scholar 

  22. Mathews, M. J., Pimenta, M. A., Dresselhaus, G., Dresselhaus, M. S. & Endo, M. Origins of dispersive effects of the Raman D band in carbon materials. Phys. Rev. B 59, R6585–R6588 (1999).

    Article  Google Scholar 

  23. Donaldson, K. et al. Carbon nanotubes: a review of their properties in relation to pulmonary toxicology workplace safety. Toxicol. Sci. 92, 5–22 (2006).

    Article  CAS  Google Scholar 

  24. Shvedova, A. A. et al. Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am. J. Physiol. Lung Cell Mol. Physiol. 289, L698–L708 (2005).

    Article  CAS  Google Scholar 

  25. Lam, C.-W., James, J. T., McCluskey, R. & Hunter, R. L. Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol. Sci. 77, 126–134 (2004).

    Article  CAS  Google Scholar 

  26. Medina, C., Santos-Martinez, M. J., Radomski, A., Corrigan, O. I. & Radomski, M. W. Nanoparticles: pharmacological and toxicological significance. Br. J. Pharmacol. 150, 552–558 (2007).

    Article  CAS  Google Scholar 

  27. Fan, X., Tan, J., Zhang, G. & Zhang, F. Isolation of carbon nanohorn assemblies and their potential for intracellular delivery. Nanotechnology 18, 195103 (2007).

    Article  Google Scholar 

  28. Rao, G. V. et al. Efficacity of a technique for exposing the mouse lung to particles aspirated from the pharynx. J. Toxicol. Environ. Health A 66, 1441–1452 (2003).

    Article  CAS  Google Scholar 

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Acknowledgements

This research was sponsored in part by the ORNL BioEnergy Science Center. The BioEnergy Science Center is a U.S. Department of Energy Bioenergy Research Center supported by the Office of Biological and Environmental Research in the DOE Office of Science. We are indebted to W. Wang and B. Gu for help with Raman spectroscopy, M. Su and Z. Hu for help with imaging setups, D. B. Geohegan and B. Zhao of ORNL for supplying pluronic coated SWCNHs, and D. Glass for help with animal experiments. We are grateful to V. Castranova at NIOSH for training with the pharyngeal aspiration and BAL techniques. ORNL is managed by UT-Battelle, LLC, for the U.S. Department of Energy under contract DE-AC05-00OR22725.

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Authors and Affiliations

  1. Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, 37831, Tennessee, USA

    Laurene Tetard, Ali Passian, Katherine T. Venmar, Rachel M. Lynch, Brynn H. Voy & Thomas Thundat

  2. Department of Physics, University of Tennessee, Knoxville, 37996-1200, Tennessee, USA

    Laurene Tetard, Ali Passian & Thomas Thundat

  3. Materials Science & Engineering department, Northwestern University, Evanston, 60208, Illinois, USA

    Gajendra Shekhawat & Vinayak P. Dravid

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  1. Laurene Tetard
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  6. Gajendra Shekhawat
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Contributions

L.T. and K.T.V. performed the experiments under the guidance of A.P. and T.T. R.M.L. and B.H.V. prepared the samples from the mice. L.T., A.P., K.T.V., B.H.V. and T.T. wrote the manuscript. L.T., A.P. and T.T. carried out revisions of the manuscript. T.T., L.T. and A.P. conceived the experiments. G.S. and V.P.D. helped with the initial assembling of the SNFUH.

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Correspondence to Ali Passian.

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Tetard, L., Passian, A., Venmar, K. et al. Imaging nanoparticles in cells by nanomechanical holography. Nature Nanotech 3, 501–505 (2008). https://doi.org/10.1038/nnano.2008.162

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