Deconvoluting hepatic processing of carbon nanotubes

• Verfasst von: Alidori, Simone [VerfasserIn]
• Verfasst von: Riabov, Vladimir [VerfasserIn]
• Verfasst von: Kzhyshkowska, Julia [VerfasserIn]
• Titel: Deconvoluting hepatic processing of carbon nanotubes
• Verf.angabe: 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
• E-Jahr: 2016
• Jahr: 29 Jul 2016
• Umfang: 11 S.
• Fussnoten: Gesehen am 02.07.2019
• Titel Quelle: Enthalten in: Nature Communications
• Ort Quelle: [London] : Springer Nature, 2010
• Jahr Quelle: 2016
• Band/Heft Quelle: 7(2016) Artikel-Nummer 12343, 11 Seiten
• ISSN Quelle: 2041-1723
• DOI: doi:10.1038/ncomms12343
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1668350599

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.