Deconvoluting hepatic processing of carbon nanotubes Journal Article

Authors: Alidori, S.; Bowman, R. L.; Yarilin, D.; Romin, Y.; Barlas, A.; Mulvey, J. J.; Fujisawa, S.; Xu, K.; Ruggiero, A.; Riabov, V.; Thorek, D. L. J.; Ulmert, H. D. S.; Brea, E. J.; Behling, K.; Kzhyshkowska, J.; Manova-Todorova, K.; Scheinberg, D. A.; McDevitt, M. R.
Article Title: Deconvoluting hepatic processing of carbon nanotubes
Abstract: Single-wall carbon nanotubes present unique opportunities for drug delivery, but have not advanced into the clinic. Differential nanotube accretion and clearance from critical organs have been observed, but the mechanism not fully elucidated. The liver has a complex cellular composition that regulates a range of metabolic functions and coincidently accumulates most particulate drugs. Here we provide the unexpected details of hepatic processing of covalently functionalized nanotubes including receptor-mediated endocytosis, cellular trafficking and biliary elimination. Ammonium-functionalized fibrillar nanocarbon is found to preferentially localize in the fenestrated sinusoidal endothelium of the liver but not resident macrophages. Stabilin receptors mediate the endocytic clearance of nanotubes. Biocompatibility is evidenced by the absence of cell death and no immune cell infiltration. Towards clinical application of this platform, nanotubes were evaluated for the first time in non-human primates. The pharmacologic profile in cynomolgus monkeys is equivalent to what was reported in mice and suggests that nanotubes should behave similarly in humans.
Keywords: mus; protein; drug development; nanoparticle; rodent; primate; carbon; macaca fascicularis; primates; bioengineering; ammonium compound
Journal Title: Nature Communications
Volume: 7
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2016-07-01
Start Page: 12343
Language: English
DOI: 10.1038/ncomms12343
PROVIDER: scopus
PMCID: PMC4974572
PUBMED: 27468684
Notes: Article -- Export Date: 1 September 2016 -- Source: Scopus
Citation Impact
MSK Authors
  1. Michael R Mcdevitt
    131 Mcdevitt
  2. Hans David Staffan Ulmert
    52 Ulmert
  3. Afsar Barlas
    28 Barlas
  4. Simone Alidori
    11 Alidori
  5. Robert L Bowman
    35 Bowman
  6. Yevgeniy Romin
    18 Romin
  7. Dmitry Yarilin
    10 Yarilin
  8. Joseph Justin Mulvey
    13 Mulvey
  9. Ke   Xu
    8 Xu
  10. Elliott Joseph Brea
    17 Brea