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Mass spectrometry imaging reveals the sub-organ distribution of carbon nanomaterials

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Abstract

Label and label-free methods to image carbon-based nanomaterials exist. However, label-based approaches are limited by the risk of tag detachment over time, and label-free spectroscopic methods have slow imaging speeds, weak photoluminescence signals and strong backgrounds. Here, we present a label-free mass spectrometry imaging method to detect carbon nanotubes, graphene oxide and carbon nanodots in mice. The large molecular weights of nanoparticles are difficult to detect using conventional mass spectrometers, but our method overcomes this problem by using the intrinsic carbon cluster fingerprint signal of the nanomaterials. We mapped and quantified the sub-organ distribution of the nanomaterials in mice. Our results showed that most carbon nanotubes and nanodots were found in the outer parenchyma of the kidney, and all three materials were seen in the red pulp of the spleen. The highest concentrations of nanotubes in the spleen were found within the marginal zone.

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Figure 1: LDI MS imaging of CNMs in mouse tissue sections.
Figure 2: Sub-organ biodistribution of CNTs in mouse spleen tissue.
Figure 3: Quantification of CNMs in organs by LDI MS.
Figure 4: Quantification of CNTs in mouse spleen tissue section.
Figure 5: LDI MS imaging of drug-loaded CNTs in mouse tumour.
Figure 6: LDI MS imaging of MoS2 nanosheets in mouse lung tissue section.

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References

  1. Jariwala, D., Sangwan, V. K., Lauhon, L. J., Marks, T. J. & Hersam, M. C. Carbon nanomaterials for electronics, optoelectronics, photovoltaics, and sensing. Chem. Soc. Rev. 42, 2824–2860 (2013).

    Article  CAS  Google Scholar 

  2. Allen, M. J., Tung, V. C. & Kaner, R. B. Honeycomb carbon: a review of graphene. Chem. Rev. 110, 132–145 (2010).

    Article  CAS  Google Scholar 

  3. Miyako, E. et al. Carbon nanotube–liposome supramolecular nanotrains for intelligent molecular-transport systems. Nature Commun. 3, 1226 (2012).

    Article  Google Scholar 

  4. Cai, D. et al. Highly efficient molecular delivery into mammalian cells using carbon nanotube spearing. Nature Methods 2, 449–454 (2005).

    Article  CAS  Google Scholar 

  5. Baker, S. N. & Baker, G. A. Luminescent carbon nanodots: emergent nanolights. Angew. Chem. Int. Ed. 49, 6726–6744 (2010).

    Article  CAS  Google Scholar 

  6. Abarrategi, A. et al. Multiwall carbon nanotube scaffolds for tissue engineering purposes. Biomaterials 29, 94–102 (2008).

    Article  CAS  Google Scholar 

  7. Yang, X., Ren, J., Qu, K. & Qu, X. Using graphene oxide high near-infrared absorbance for photothermal treatment of Alzheimer's disease. Adv. Mater. 24, 1722–1728 (2012).

    Article  Google Scholar 

  8. Srikanth, M. & Kessler, J. A. Nanotechnology-novel therapeutics for CNS disorders. Nature Rev. Neurol. 8, 307–318 (2012).

    Article  CAS  Google Scholar 

  9. Kostarelos, K., Bianco, A. & Prato, M. Promises, facts and challenges for carbon nanotubes in imaging and therapeutics. Nature Nanotech. 4, 626–633 (2009).

    Article  Google Scholar 

  10. Hu, X. & Zhou, Q. Health and ecosystem risks of graphene. Chem. Rev. 113, 3815–3835 (2013).

    Article  CAS  Google Scholar 

  11. Mao, H. Y. et al. Graphene: promises, facts, opportunities, and challenges in nanomedicine. Chem. Rev. 113, 3407–3424 (2013).

    Article  CAS  Google Scholar 

  12. Schipper, M. L. et al. A pilot toxicology study of single-walled carbon nanotubes in a small sample of mice. Nature Nanotech. 3, 216–221 (2008).

    Article  CAS  Google Scholar 

  13. Georgin, D. et al. Preparation of 14C-labeled multiwalled carbon nanotubes for biodistribution investigations. J. Am. Chem. Soc. 131, 14658–14659 (2009).

    Article  CAS  Google Scholar 

  14. Yang, S. et al. Biodistribution of pristine single-walled carbon nanotubes in vivo. J. Phys. Chem. C 111, 17761–17764 (2007).

    Article  CAS  Google Scholar 

  15. Singh, R. et al. Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers. Proc. Natl Acad. Sci. USA 103, 3357–3362 (2006).

    Article  CAS  Google Scholar 

  16. Huang, X. L. et al. Effect of injection routes on the biodistribution, clearance, and tumor uptake of carbon dots. ACS Nano 7, 5684–5693 (2013).

    Article  CAS  Google Scholar 

  17. Liu, Z. et al. Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy. Proc. Natl Acad. Sci. USA 105, 1410–1415 (2008).

    Article  CAS  Google Scholar 

  18. Leeuw, T. K. et al. Single-walled carbon nanotubes in the intact organism—near-IR imaging and biocompatibility studies in Drosophila. Nano Lett. 7, 2650–2654 (2007).

    Article  CAS  Google Scholar 

  19. Welsher, K., Sherlock, S. P. & Dai, H. Deep-tissue anatomical imaging of mice using carbon nanotube fluorophores in the second near-infrared window. Proc. Natl Acad. Sci. USA 108, 8943–8948 (2011).

    Article  CAS  Google Scholar 

  20. Avti, P. K. et al. Detection, mapping, and quantification of single walled carbon nanotubes in histological specimens with photoacoustic microscopy. PLoS ONE 7, e35064 (2012).

    Article  CAS  Google Scholar 

  21. Zhang, H. F., Maslov, K., Stoica, G. & Wang, L. V. Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging. Nature Biotechnol. 24, 848–851 (2006).

    Article  CAS  Google Scholar 

  22. Tong, L. et al. Label-free imaging of semiconducting and metallic carbon nanotubes in cells and mice using transient absorption microscopy. Nature Nanotech. 7, 56–61 (2012).

    Article  CAS  Google Scholar 

  23. Berry, K. A. Z. et al. MALDI imaging of lipid biochemistry in tissues by mass spectrometry. Chem. Rev. 111, 6491–6512 (2011).

    Article  Google Scholar 

  24. Cornett, D. S., Reyzer, M. L., Chaurand, P. & Caprioli, R. M. MALDI imaging mass spectrometry: molecular snapshots of biochemical systems. Nature Methods 4, 828–833 (2007).

    Article  CAS  Google Scholar 

  25. Chughtai, K. & Heeren, R. M. A. Mass spectrometric imaging for biomedical tissue analysis. Chem. Rev. 110, 3237–3277 (2010).

    Article  CAS  Google Scholar 

  26. Ellis, S. R., Bruinen, A. L. & Heeren, R. M. A critical evaluation of the current state-of-the-art in quantitative imaging mass spectrometry. Anal. Bioanal. Chem. 406, 1275–1289 (2014).

    Article  CAS  Google Scholar 

  27. Yan, B. et al. Multiplexed imaging of nanoparticles in tissues using laser desorption/ionization mass spectrometry. J. Am. Chem. Soc. 135, 12564–12567 (2013).

    Article  CAS  Google Scholar 

  28. Zhu, Z-J., Ghosh, P. S., Miranda, O. R., Vachet, R. W. & Rotello, V. M. Multiplexed screening of cellular uptake of gold nanoparticles using laser desorption/ionization mass spectrometry. J. Am. Chem. Soc. 130, 14139–14143 (2008).

    Article  CAS  Google Scholar 

  29. Orden, A. V. & Saykally, R. J. Small carbon clusters: spectroscopy, structure, and energetics. Chem. Rev. 98, 2313–2357 (1998).

    Article  Google Scholar 

  30. Belau, L. et al. Ionization thresholds of small carbon clusters: tunable VUV experiments and theory. J. Am. Chem. Soc. 129, 10229–10243 (2007).

    Article  CAS  Google Scholar 

  31. Chen, S. et al. Carbon nanodots as a matrix for the analysis of low-molecular-weight molecules in both positive- and negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and quantification of glucose and uric acid in real samples. Anal. Chem. 85, 6646–6652 (2013).

    Article  CAS  Google Scholar 

  32. Liu, J. H., Yang, S. T., Wang, H. F. & Liu, Y. F. Advances in biodistribution study and tracing methodology of carbon nanotubes. J. Nanosci. Nanotechnol. 10, 8469–8481 (2010).

    Article  CAS  Google Scholar 

  33. Zhang, X. et al. Distribution and biocompatibility studies of graphene oxide in mice after intravenous administration. Carbon 49, 986–995 (2011).

    Article  CAS  Google Scholar 

  34. Tao, H. et al. In vivo NIR fluorescence imaging, biodistribution, and toxicology of photoluminescent carbon dots produced from carbon nanotubes and graphite. Small 8, 281–290 (2011).

    Article  Google Scholar 

  35. Lacerda, L. et al. Tissue histology and physiology following intravenous administration of different types of functionalized multiwalled carbon nanotubes. Nanomedicine 3, 149–161 (2008).

    Article  CAS  Google Scholar 

  36. Choi, H. S. et al. Renal clearance of quantum dots. Nature Biotechnol. 25, 1165–1170 (2007).

    Article  CAS  Google Scholar 

  37. Longmire, M., Choyke, P. L. & Kobayashi, H. Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. Nanomedicine 3, 703–717 (2008).

    Article  CAS  Google Scholar 

  38. Zhou, C. et al. Near-infrared emitting radioactive gold nanoparticles with molecular pharmacokinetics. Angew. Chem. Int. Ed. 51, 10118–10122 (2012).

    Article  CAS  Google Scholar 

  39. Mebius, R. E. & Kraal, G. Structure and function of the spleen. Nature Rev. Immunol. 5, 606–616 (2005).

    Article  CAS  Google Scholar 

  40. Szájli, E., Fehér, T. & Medzihradszky, K. F. Investigating the quantitative nature of MALDI-TOF MS. Mol. Cell. Proteomics 7, 2410–2418 (2008).

    Article  Google Scholar 

  41. Duncan, M. W., Roder, H. & Hunsucker, S. W. Quantitative matrix-assisted laser desorption/ionization mass spectrometry. Brief. Funct. Genomic Proteomic 7, 355–370 (2008).

    Article  CAS  Google Scholar 

  42. Pirman, D. A., Reich, R. F., Kiss, A., Heeren, R. M. & Yost, R. A. Quantitative MALDI tandem mass spectrometric imaging of cocaine from brain tissue with a deuterated internal standard. Anal. Chem. 85, 1081–1089 (2013).

    Article  CAS  Google Scholar 

  43. Liu, J-H. et al. Effect of size and dose on the biodistribution of graphene oxide in mice. Nanomedicine 7, 1801–1812 (2012).

    Article  CAS  Google Scholar 

  44. Almeida, J. P. M., Chen, A. L., Foster, A. & Drezek, R. In vivo biodistribution of nanoparticles. Nanomedicine 6, 815–835 (2011).

    Article  CAS  Google Scholar 

  45. Koeniger, S. L. et al. A quantitation method for mass spectrometry imaging. Rapid Commun. Mass Spectrom. 25, 503–510 (2011).

    Article  CAS  Google Scholar 

  46. Lagarrigue, M. et al. Localization and in situ absolute quantification of chlordecone in the mouse liver by MALDI imaging. Anal. Chem. 86, 5775–5783 (2014).

    Article  CAS  Google Scholar 

  47. Edelson-Averbukh, M., Pipkorn, R. & Lehmann, W. D. Phosphate group-driven fragmentation of multiply charged phosphopeptide anions. Improved recognition of peptides phosphorylated at serine, threonine, or tyrosine by negative ion electrospray tandem mass spectrometry. Anal. Chem. 78, 1249–1256 (2006).

    Article  CAS  Google Scholar 

  48. Kauppila, T. J., Kotiaho, T., Kostiainen, R. & Bruins, A. P. Negative ion-atmospheric pressure photoionization-mass spectrometry. J. Am. Soc. Mass Spectrom. 15, 203–211 (2004).

    Article  CAS  Google Scholar 

  49. National Research Council Guide for the Care and Use of Laboratory Animals: Eighth Edition (The National Academies Press, 2011).

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Acknowledgements

This work was supported by grants from the National Natural Sciences Foundation of China (grants 21127901, 21321003, 21175139, 21305144 and 21205123) and the Chinese Academy of Sciences. A.B-T. acknowledges support from ‘The Ohio State University Start-up Funds’. The authors thank R. Graham Cooks and A. Tao for discussions.

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Authors and Affiliations

Authors

Contributions

Z.X.N. and S.M.C. conceived and designed the experiments. S.M.C. performed the experiments. C.Q.X., H.H.L. and Q.H. helped with animal care. S.M.C. and Q.Q.W. analysed the data. Q.Q.W. and H.H.L. contributed to cell culture. J.H. helped with TEM analysis. S.M.C., A.B-T. and Z.X.N. co-wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to Zongxiu Nie.

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The authors declare no competing financial interests.

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Chen, S., Xiong, C., Liu, H. et al. Mass spectrometry imaging reveals the sub-organ distribution of carbon nanomaterials. Nature Nanotech 10, 176–182 (2015). https://doi.org/10.1038/nnano.2014.282

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