In cancer imaging, nanoparticle biodistribution is typically visualized in living subjects using ‘bulk’ imaging modalities such as magnetic resonance imaging, computerized tomography and whole-body fluorescence. Accordingly, nanoparticle influx is observed only macroscopically, and the mechanisms by which they target cancer remain elusive. Nanoparticles are assumed to accumulate via several targeting mechanisms, particularly extravasation (leakage into tumour). Here, we show that, in addition to conventional nanoparticle-uptake mechanisms, single-walled carbon nanotubes are almost exclusively taken up by a single immune cell subset, Ly-6Chi monocytes (almost 100% uptake in Ly-6Chi monocytes, below 3% in all other circulating cells), and delivered to the tumour in mice. We also demonstrate that a targeting ligand (RGD) conjugated to nanotubes significantly enhances the number of single-walled carbon nanotube-loaded monocytes reaching the tumour (P < 0.001, day 7 post-injection). The remarkable selectivity of this tumour-targeting mechanism demonstrates an advanced immune-based delivery strategy for enhancing specific tumour delivery with substantial penetration.
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This work was supported by a number of grants. B.R.S. was supported by a National Institutes of Health (NIH) 25T post-doctoral training grant and is currently supported by a K99/R00 award (K99 CA160764). S.S.G. was supported by a Center for Cancer Nanotechnology Excellence–Translation (CCNE-T)-grant (National Cancer Institute U54 CA119367) and in vivo cellular and molecular imaging (ICMIC) grant (P50 CA114747). The authors thank C. Ball for discussions related to this work. The authors acknowledge technical assistance in experiments and analysis from M. Philips, S. Tabakman, J. Rosenberg, S. Kusy, C. Nielsen, H. Dai, A-L. Koh, R. Sinclair, C. Zavaleta, J. Strommer and CytoViva.
The authors declare no competing financial interests.
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Smith, B., Ghosn, E., Rallapalli, H. et al. Selective uptake of single-walled carbon nanotubes by circulating monocytes for enhanced tumour delivery. Nature Nanotech 9, 481–487 (2014). https://doi.org/10.1038/nnano.2014.62
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