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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References
Nel, A., Xia, T., Madler, L. & Li, N. Toxic potential of materials at the nanolevel. Science 311, 622–627 (2006).
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).
Stone, V. & Donaldson, K. Signs of stress. Nature Nanotech. 1, 23–24 (2006).
Colvin, V. L. The potential environmental impact of engineered nanomaterials. Nature Biotechnol. 21, 1166–1170 (2003).
Borm, P. et al. The potential risks of nanomaterials : a review carried out for ECETOC. Part. Fibre Toxicol. 3, 11–46 (2006).
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).
Oberdörster, G., Oberdörster, E. & Oberdörster, J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect. 113, 823–839 (2005).
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).
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).
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).
Porter, A. E. et al. Direct imaging of single-walled carbon nanotubes in cells. Nature Nanotech. 2, 713–717 (2007).
Rabe, U. & Arnold, W. Acoustic microscopy by atomic force microscopy. Appl. Phys. Lett. 64, 1493–1495 (1994).
Kolosov, O. V. et al. Imaging the elastic nanostructure of Ge islands by ultrasonic force microscopy. Phys. Rev. Lett. 81, 1046–1049 (1998).
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).
Sahin, O. et al. An atomic force microscope tip designed to measure time-varying nanomechanical forces. Nature Nanotech. 2, 507–514 (2007).
Garcia, R., Margerle, R. & Perez, R. Nanoscale compositional mapping with gentle forces. Nature Mater. 6, 405–411 (2007).
Shekhawat, G. S. & Dravid, V. P. Nanoscale imaging of buried structures via scanning near-field ultrasound holography. Science 310, 89–92 (2005).
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).
Kreyling, W. G., Semmler-Behnke, M. & Moller, W. Health implications of nanoparticles. J. Nanopart. Res. 8, 543–562 (2006).
Iijima, S. et al. Nano-aggregates of single-walled graphitic carbon nano-horns. Chem. Phys. Lett. 309, 165–170 (1999).
Tuinstra, F. & Koenig, J. L. Raman spectrum of graphite. J. Chem. Phys. 53, 1126–1130 (1970).
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).
Donaldson, K. et al. Carbon nanotubes: a review of their properties in relation to pulmonary toxicology workplace safety. Toxicol. Sci. 92, 5–22 (2006).
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).
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).
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).
Fan, X., Tan, J., Zhang, G. & Zhang, F. Isolation of carbon nanohorn assemblies and their potential for intracellular delivery. Nanotechnology 18, 195103 (2007).
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).
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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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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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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DOI: https://doi.org/10.1038/nnano.2008.162
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