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 and Michael R. McDevitt ()
Additional contact information
Simone Alidori: Memorial Sloan-Kettering Cancer Center
Robert L. Bowman: Memorial Sloan-Kettering Cancer Center
Dmitry Yarilin: Molecular Cytology Core Facility, Memorial Sloan-Kettering Cancer Center
Yevgeniy Romin: Molecular Cytology Core Facility, Memorial Sloan-Kettering Cancer Center
Afsar Barlas: Molecular Cytology Core Facility, Memorial Sloan-Kettering Cancer Center
J. Justin Mulvey: Memorial Sloan-Kettering Cancer Center
Sho Fujisawa: Molecular Cytology Core Facility, Memorial Sloan-Kettering Cancer Center
Ke Xu: Molecular Cytology Core Facility, Memorial Sloan-Kettering Cancer Center
Alessandro Ruggiero: Papworth Hospital NHS Foundation Trust, Cambridge University Health Partners
Vladimir Riabov: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Ruprecht-Karls University of Heidelberg
Daniel L. J. Thorek: Johns Hopkins School of Medicine
Hans David S. Ulmert: Memorial Sloan-Kettering Cancer Center
Elliott J. Brea: Memorial Sloan-Kettering Cancer Center
Katja Behling: Memorial Sloan-Kettering Cancer Center
Julia Kzhyshkowska: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Ruprecht-Karls University of Heidelberg
Katia Manova-Todorova: Molecular Cytology Core Facility, Memorial Sloan-Kettering Cancer Center
David A. Scheinberg: Memorial Sloan-Kettering Cancer Center
Michael R. McDevitt: Memorial Sloan-Kettering Cancer Center

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12343

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