title: Selective uptake of single-walled carbon nanotubes by circulating monocytes for enhanced tumour delivery.
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.
authors.affiliation: 1] Molecular Imaging Program at Stanford, The James H Clark Center, Stanford University, Stanford, California 94305, USA [2] Department of Radiology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Bryan Ronain
authors.initials: BR
authors.lastname: Smith
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Eliver Eid Bou
authors.initials: EE
authors.lastname: Ghosn
authors.affiliation: Molecular Imaging Program at Stanford, The James H Clark Center, Stanford University, Stanford, California 94305, USA.
authors.forename: Harikrishna
authors.initials: H
authors.lastname: Rallapalli
authors.affiliation: 1] Molecular Imaging Program at Stanford, The James H Clark Center, Stanford University, Stanford, California 94305, USA [2].
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Prescher
authors.affiliation: 1] Molecular Imaging Program at Stanford, The James H Clark Center, Stanford University, Stanford, California 94305, USA [2] Department of Radiology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Larson
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Leonore A
authors.initials: LA
authors.lastname: Herzenberg
authors.affiliation: 1] Molecular Imaging Program at Stanford, The James H Clark Center, Stanford University, Stanford, California 94305, USA [2] Department of Radiology, Stanford University School of Medicine, Stanford, California 94305, USA [3] Department of Bioengineering and Department of Materials Science & Engineering, Stanford University, Stanford, California 94305, USA.
authors.forename: Sanjiv Sam
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D051379:Mice; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D037742:Nanotubes, Carbon; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy
chemical_list: D037742:Nanotubes, Carbon
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