Single-walled carbon nanotubes (SWNTs) exhibit unique size, shape and physical properties1,2,3 that make them promising candidates for biological applications. Here, we investigate the biodistribution of radio-labelled SWNTs in mice by in vivo positron emission tomography (PET), ex vivo biodistribution and Raman spectroscopy. It is found that SWNTs that are functionalized with phospholipids bearing polyethylene-glycol (PEG) are surprisingly stable in vivo. The effect of PEG chain length on the biodistribution and circulation of the SWNTs is studied. Effectively PEGylated SWNTs exhibit relatively long blood circulation times and low uptake by the reticuloendothelial system (RES). Efficient targeting of integrin positive tumour in mice is achieved with SWNTs coated with PEG chains linked to an arginine–glycine–aspartic acid (RGD) peptide. A high tumour accumulation is attributed to the multivalent effect of the SWNTs. The Raman signatures of SWNTs are used to directly probe the presence of nanotubes in mice tissues and confirm the radio-label-based results.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $15.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Dresselhaus, M. & Dai, H. (eds) MRS 2004 Carbon Nanotube Special Issue (2004).
Dresselhaus, M. S., Dresselhaus, G. & Avouris, P. (eds) Carbon Nanotubes (Springer, Berlin, 2001).
Dai, H. Carbon nanotubes: opportunities and challenges. Surf. Sci. 500, 218–241 (2002).
Chen, R. J. et al. Noncovalent functionalization of carbon nanotubes for highly specific electronic biosensors. Proc. Natl Acad. Sci. USA 100, 4984–4989 (2003).
Kam, N. W. S., Jessop, T. C., Wender, P. A. & Dai, H. J. Nanotube molecular transporters: Internalization of carbon nanotube–protein conjugates into mammalian cells. J. Am. Chem. Soc. 126, 6850–6851 (2004).
Pantarotto, D., Briand, J., Prato, M. & Bianco, A. Translocation of bioactive peptides across cell membranes by carbon nanotubes. Chem. Commun. 16–17 (2004).
Bianco, A., Kostarelos, K., Partidos, C. D. & Prato, M. Biomedical applications of functionalised carbon nanotubes. Chem. Commun. 571–577 (2005).
Cherukuri, P., Bachilo, S. M., Litovsky, S. H. & Weisman, R. B. Near-infrared fluorescence microscopy of single-walled carbon nanotubes in phagocytic cells. J. Am. Chem. Soc. 126, 15638–15639 (2004).
Liu, Y. et al. Polyethylenimine-grafted multiwalled carbon nanotubes for secure noncovalent immobilization and efficient delivery of DNA. Angew. Chem. Int. Edn Engl. 44, 4782 (2005).
Kam, N. W. S., Liu, Z. & Dai, H. Functionalization of carbon nanotubes via cleavable disulfide bonds for efficient intracellular delivery of siRNA and potent gene silencing. J. Am. Chem. Soc. 127, 12492–12493 (2005).
Kam, N. W. S., O'Connell, M., Wisdom, J. A. & Dai, H. Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction. Proc. Natl Acad. Sci. USA 102, 11600–11605 (2005).
Kam, N. W. S., Liu, Z. & Dai, H. J. Carbon nanotubes as intracellular transporters for proteins and DNA: An investigation of the uptake mechanism and pathway. Angew. Chem. Int. Edn Engl. 45, 577–581 (2005).
Kam, N. W. S. & Dai, H. Carbon nanotubes as intracellular protein transporters: Generality and biological functionality. J. Am. Chem. Soc. 127, 6021–6026 (2005).
Sayes, C. M. et al. Functionalization density dependence of single-walled carbon nanotubes cytotoxicity in vitro. Toxicity Lett. 161, 135–142 (2006).
Chen, X. et al. Interfacing carbon nanotubes with living cells. J. Am. Chem. Soc. 128, 6292–6293 (2006).
Dumortier, H. et al. Functionalized carbon nanotubes are non-cytotoxic and preserve the functionality of primary immune cells. Nano Lett. 6, 1522–1528 (2006).
Wang, H. F. et al. Biodistribution of carbon single-wall carbon nanotubes in mice. J. Nanosci. Nanotechnol. 4, 1019–1024 (2004).
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).
Moghimi, S. M., Hunter, A. C. & Murray, J. C. Long-circulating and target-specific nanoparticles: Theory to practice. Pharmacol. Rev. 53, 283–318 (2001).
Moghimi, S. M., Hunter, A. C. & Murray, J. C. Nanomedicine: current status and future prospects. FASEB J. 19, 311–330 (2005).
Mizejewski, G. J. Role of integrins in cancer: Survey of expression patterns. Proc. Soc. Exp. Biol. Med. 222, 124–138 (1999).
Jin, H. & Varner, J. Integrins: Roles in cancer development and as treatment targets. Br. J. Cancer 90, 561–565 (2004).
Xiong, J. P. et al. Crystal structure of the extracellular segment of integrin αvβ3 in complex with an Arg-Gly-Asp ligand. Science 296, 151 (2002).
Cai, W. et al. Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects. Nano Lett. 6, 669–676 (2006).
Cai, W. et al. In vitro and in vivo characterization of 64Cu-labeled AbegrinTM, a humanized monoclonal antibody against integrin αvβ3 . Cancer Res. 66, 9673 (2006).
Chen, X. et al. Pegylated Arg-Gly-Asp peptide: 64Cu labeling and PET imaging of brain tumor αvβ3-integrin expression. J. Nucl. Med. 45, 1776–1783 (2004).
Heller, D. A., Baik, S., Eurell, T. E. & Strano, M. S. Single-walled carbon nanotube spectroscopy in live cells: Towards long-term labels and optical sensors. Adv. Mater. 17, 2793–2799 (2005).
Jain, R. K. Vascular and interstital barriers to delivery of therapeutic agents in tumors. Cancer Metastasis Rev. 9, 253–266 (1990).
Wu, Y. et al. MicroPET imaging of glioma integrin αvβ3 expression using 64Cu-labeled tetrameric RGD peptide. J. Nucl. Med. 46, 1707–1718 (2005).
Cai, W., Zhang, X., Wu, Y. & Chen, X. A thiol-reactive 18F-labeling agent, N-[2-(4-18F-fluorobenzamido)ethyl]maleimide (18F-FBEM), and the synthesis of RGD peptide-based tracer for PET imaging of αvβ3 integrin expression. J. Nucl. Med. 47, 1172–1180. (2006).
This work was supported in part by a Ludwig Translational Research Grant at Stanford University and NIH-NCI CCNE-TR at Stanford (H.D.), National Institute of Biomedical Imaging and Bioengineering (NIBIB) (R21 EB001785), National Cancer Institute (NCI) (R21 CA102123, P50 CA114747, U54 CA119367, R24 CA93862), Department of Defense (DOD) (W81XWH-04-1-0697, W81XWH-06-1-0665, W81XWH-06-1-0042, DAMD17-03-1-0143) and a Benedict Cassen Postdoctoral Fellowship from the Education and Research Foundation of the Society of Nuclear Medicine (to W.C.).
The authors declare no competing financial interests.
About this article
Graphene nano-ribbon based high potential and efficiency for DNA, cancer therapy and drug delivery applications
Drug Metabolism Reviews (2019)
Current Drug Metabolism (2019)
Inorganica Chimica Acta (2019)
An overview of active and passive targeting strategies to improve the nanocarriers efficiency to tumour sites
Journal of Pharmacy and Pharmacology (2019)
Inorganic Nanoparticles as Drug Delivery Systems and Their Potential Role in the Treatment of Chronic Myelogenous Leukaemia
Technology in Cancer Research & Treatment (2019)