Skip to main content

Carbon Nanotube Uptake and Toxicity in the Brain

  • Protocol
  • First Online:
Book cover Carbon Nanotubes

Part of the book series: Methods in Molecular Biology ((MIMB,volume 625))

Abstract

The development of novel drug delivery systems is essential for the improvement of therapeutics for most human diseases. Currently used cellular delivery systems, such as viral vectors, liposomes, cationic lipids, and polymers, may have limited clinical efficacy because of safety issues, low gene transfer efficiency, or cytotoxicity. Carbon nanotubes (CNTs) have garnered much interest as possible biological vectors after the recent discovery of their capacity to penetrate cells. Inspite of the prominence of CNT studies in the nanotechnology literature, exploration of their application to central nervous system (CNS) therapeutics is at a very early stage. Before CNTs are used for treatment of brain and spinal cord disorders, however, several issues such as their CNS penetration and toxicity need to be addressed. Here, we discuss methods by which CNT uptake and toxicity can be assessed in animal models.

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bechmann I, Galea I, Perry VH (2007) What is the blood-brain barrier (not)? Trends Immunol 28:5-11

    Article  CAS  PubMed  Google Scholar 

  2. Muldoon LL, Soussain C, Jahnke K, Johanson C, Siegal T, Smith QR, Hall WA, Hynynen K, Senter PD, Peereboom DM, Neuwelt EA (2007) Chemotherapy delivery issues in central nervous system malignancy: a reality check. J Clin Oncol 25:2295-2305

    Article  CAS  PubMed  Google Scholar 

  3. Galea I, Bechmann I, Perry VH (2007) What is immune privilege (not)? Trends Immunol 28:12-18

    Article  CAS  PubMed  Google Scholar 

  4. Djukic M (2006) Circulating monocytes engraft in the brain, differentiate into microglia and contribute to the pathology following meningitis in mice. Brain 129:2394-2403

    Article  PubMed  Google Scholar 

  5. Jain KK (2007) Use of nanoparticles for drug delivery in glioblastoma multiforme. Expert Rev Neurother 7:363-372

    Article  CAS  PubMed  Google Scholar 

  6. Pardridge WM (2007) Drug targeting to the brain. Pharm Res 24:1733-1744

    Article  CAS  PubMed  Google Scholar 

  7. Badie B, Schartner JM (2000) Flow cytometric characterization of tumor-associated macrophages in experimental gliomas. Neuro­surgery 46: 957-961; discussion 61-62

    Google Scholar 

  8. Roggendorf W, Strupp S, Paulus W (1996) Distribution and characterization of microglia/macrophages in human brain tumors. Acta Neuropathol 92:288-293

    Article  CAS  PubMed  Google Scholar 

  9. Shinonaga M, Chang CC, Suzuki N, Sato M, Kuwabara T (1988) Immunohistological evaluation of macrophage infiltrates in brain tumors. Correlation with peritumoral edema. J Neurosurg 68:259-265

    Article  CAS  PubMed  Google Scholar 

  10. Streit WJ (1994) Cellular immune response in brain tumors. Neuropathol Appl Neurobiol 20:205-206

    CAS  PubMed  Google Scholar 

  11. Hussain SF, Yang D, Suki D, Grimm E, Heimberger A (2006) Innate immune functions of microglia isolated from human glioma patients. J Transl Med 4:15

    Article  PubMed  Google Scholar 

  12. Nickles D, Abschuetz A, Zimmer H, Kees T, Geibig R, Spiess E, Regnier-Vigouroux A (2008) End-stage dying glioma cells are engulfed by mouse microglia with a strain-dependent efficacy. J Neuroimmunol 197:10-20

    Article  CAS  PubMed  Google Scholar 

  13. Kateb B, Van Handel M, Zhang L, Bronikowski MJ, Manohara H, Badie B (2007) Internalization of MWCNTs by microglia: possible application in immunotherapy of brain tumors. Neuroimage 37(Suppl 1):S9-S17

    Article  PubMed  Google Scholar 

  14. Klumpp C, Kostarelos K, Prato M, Bianco A (2006) Functionalized carbon nanotubes as emerging nanovectors for the delivery of therapeutics. Biochim Biophys Acta 1758:404-412

    Article  CAS  PubMed  Google Scholar 

  15. Liu Z, Chen K, Davis C, Sherlock S, Cao Q, Chen X, Dai H (2008) Drug delivery with carbon nanotubes for in vivo cancer treatment. Cancer Res 68:6652-6660

    Article  CAS  PubMed  Google Scholar 

  16. Pantarotto D, Partidos CD, Hoebeke J, Brown F, Kramer E, Briand JP, Muller S, Prato M, Bianco A (2003) Immunization with peptide-functionalized carbon nanotubes enhances virus-specific neutralizing antibody responses. Chem Biol 10:961-966

    Article  CAS  PubMed  Google Scholar 

  17. Pantarotto D, Singh R, McCarthy D, Erhardt M, Briand JP, Prato M, Kostarelos K, Bianco A (2004) Functionalized carbon nanotubes for plasmid DNA gene delivery. Angew Chem Int Ed Engl 43:5242-5246

    Article  CAS  PubMed  Google Scholar 

  18. Singh R, Pantarotto D, Lacerda L, Pastorin G, Klumpp C, Prato M, Bianco A, Kostarelos K (2006) Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers. Proc Natl Acad Sci U S A 103:3357-3362

    Article  CAS  PubMed  Google Scholar 

  19. Zhang Z, Yang X, Zhang Y, Zeng B, Wang S, Zhu T, Roden RB, Chen Y, Yang R (2006) Delivery of telomerase reverse transcriptase small interfering RNA in complex with positively charged single-walled carbon nanotubes suppresses tumor growth. Clin Cancer Res 12:4933-4939

    Article  CAS  PubMed  Google Scholar 

  20. Lacerda L, Bianco A, Prato M, Kostarelos K (2006) Carbon nanotubes as nanomedicines: from toxicology to pharmacology. Adv Drug Deliv Rev 58:1460-1470

    Article  CAS  PubMed  Google Scholar 

  21. Shvedova AA, Kisin ER, Mercer R, Murray AR, Johnson VJ, Potapovich AI, Tyurina YY, Gorelik O, Arepalli S, Schwegler-Berry D, Hubbs AF, Antonini J, Evans DE, Ku BK, Ramsey D, Maynard A, Kagan VE, Castranova V, Baron P (2005) Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am J Physiol Lung Cell Mol Physiol 289:L698-L708

    Article  CAS  PubMed  Google Scholar 

  22. Nemmar A, Hoet PH, Vandervoort P, Dinsdale D, Nemery B, Hoylaerts MF (2007) Enhanced peripheral thrombogenicity after lung inflammation is mediated by platelet-leukocyte activation: role of P-selectin. J Thromb Haemost 5:1217-1226

    Article  CAS  PubMed  Google Scholar 

  23. Lam CW, James JT, McCluskey R, Hunter RL (2004) Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol Sci 77:126-134

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the American Cancer Society Research Scholar Grant (RSG-03-142-01-CNE) and James S. McDonnell Foundation. The City of Hope Flow Cytometry Core was equipped in part through funding provided by ONR N00014-02-1 0958, DOD 1435-04-03GT-73134, and NSF DBI-9970143.

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Humana Press, a part of Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Zhang, L., Alizadeh, D., Badie, B. (2010). Carbon Nanotube Uptake and Toxicity in the Brain. In: Balasubramanian, K., Burghard, M. (eds) Carbon Nanotubes. Methods in Molecular Biology, vol 625. Humana Press. https://doi.org/10.1007/978-1-60761-579-8_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-579-8_6

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60761-577-4

  • Online ISBN: 978-1-60761-579-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics