Selective uptake of single-walled carbon nanotubes by circulating monocytes for enhanced tumour delivery

Nat Nanotechnol. 2014 Jun;9(6):481-7. doi: 10.1038/nnano.2014.62. Epub 2014 Apr 13.

Abstract

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-6C(hi) monocytes (almost 100% uptake in Ly-6C(hi) 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Drug Delivery Systems / methods*
  • Mice
  • Monocytes / metabolism*
  • Monocytes / pathology
  • Nanotubes, Carbon*
  • Neoplasms, Experimental* / metabolism
  • Neoplasms, Experimental* / pathology
  • Neoplasms, Experimental* / therapy

Substances

  • Nanotubes, Carbon