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In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice


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.

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Figure 1: Water-soluble carbon nanotubes functionalized with PEG, radio labels and RGD peptide.
Figure 2: Functionalization-dependent biodistribution and blood circulation of intravenously injected SWNTs in mice bearing the U87MG human glioblastoma tumour.
Figure 3: Biodistribution and retained activity of 64Cu -labelled SWNTs in mice.
Figure 4: Targeting of integrin αvβ3-positive U87MG tumour in mice by RGD-functionalized SWNTs.
Figure 5: Detecting nanotubes in mice tissues using characteristic Raman signatures of SWNTs.


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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.).

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H.D., X.C., Z.L. and W.C. conceived and designed the experiments. Z.L, W.C, X.C., L.H., N.N. K.C. and X.S. performed the experiments. H.D., Z.L., W.C. and X.C. co-wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Xiaoyuan Chen or Hongjie Dai.

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The authors declare no competing financial interests.

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Liu, Z., Cai, W., He, L. et al. In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. Nature Nanotech 2, 47–52 (2007).

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