Deconvoluting hepatic processing of carbon nanotubes

Simone Alidori, Robert L. Bowman, Dmitry Yarilin, Yevgeniy Romin, Afsar Barlas, J. Justin Mulvey, Sho Fujisawa, Ke Xu, Alessandro Ruggiero, Vladimir Riabov, Daniel L.J. Thorek, Hans David S. Ulmert, Elliott J. Brea, Katja Behling, Julia Kzhyshkowska, Katia Manova-Todorova, David A. Scheinberg, Michael R. McDevitt

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number12343
JournalNature communications
Volume7
DOIs
StatePublished - Jul 29 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    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. (2016). Deconvoluting hepatic processing of carbon nanotubes. Nature communications, 7, [12343]. https://doi.org/10.1038/ncomms12343