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. Lastly, the pharmacologic profile in cynomolgus monkeys is equivalent to what was reported in mice and suggests that nanotubes should behave similarly in humans.
- Authors:
-
[9]
- Memorial Sloan-Kettering Cancer Center, New York, NY (United States). Dept. of Radiology
- Memorial Sloan-Kettering Cancer Center, New York, NY (United States). Dept. of Molecular Pharmacology and Chemistry
- Memorial Sloan-Kettering Cancer Center, New York, NY (United States). Molecular Cytology Core Facility
- Papworth Hospital NHS Foundation Trust, Cambridge (United Kingdom). Dept. of Radiology
- Ruprecht-Karls Univ. of Heidelberg, Mannheim (Germany). Inst. of Transfusion Medicine and Immunology; Tomsk State Univ., Tomsk (Russia). Lab. for Translational Cellular and Molecular Biomedicine
- Johns Hopkins Univ., Baltimore, MD (United States). Department of Radiology and Radiological Sciences
- Ruprecht-Karls Univ. of Heidelberg, Mannheim (Germany). Inst. of Transfusion Medicine and Immunology; Tomsk State Univ., Tomsk (Russia). Lab. for Translational Cellular and Molecular Biomedicine; Red Cross Blood Service Baden-Wurttemberg-Hessen, Mannheim (Germany)
- Memorial Sloan-Kettering Cancer Center, New York, NY (United States). Dept. of Molecular Pharmacology and Chemistry; Weill Cornell Medical College, New York, NY (United States). Dept. of Pharmacology
- Memorial Sloan-Kettering Cancer Center, New York, NY (United States). Dept. of Radiology; Weill Cornell Medical College, New York, NY (United States). Dept. of Medicine
- Publication Date:
- Research Org.:
- Sloan-Kettering Inst. For Cancer Research, Inc. (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); CMINT; Commonwealth Foundation for Cancer Research; Center for Experimental Therapeutics of Memorial Sloan-Kettering Cancer Center
- OSTI Identifier:
- 1326670
- Grant/Contract Number:
- SC0002456; GM07739; R21 CA128406; R01 CA166078; R24 CA83084; R01 CA55349; R25T CA046945; P30 CA008748; P01 CA33049; F31 CA167863
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Communications
- Additional Journal Information:
- Journal Volume: 7; Journal ID: ISSN 2041-1723
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 77 NANOSCIENCE AND NANOTECHNOLOGY; nanotube
Citation Formats
Alidori, Simone, Bowman, Robert L., Yarilin, Dmitry, Romin, Yevgeniy, Barlas, Afsar, Mulvey, J. Justin, Fujisawa, Sho, Xu, Ke, Ruggiero, Alessandro, Riabov, Vladimir, Thorek, Daniel L. J., Ulmert, Hans David S., Brea, Elliott J., Behling, Katja, Kzhyshkowska, Julia, Manova-Todorova, Katia, Scheinberg, David A., and McDevitt, Michael R. Deconvoluting hepatic processing of carbon nanotubes. United States: N. p., 2016.
Web. doi:10.1038/ncomms12343.
Alidori, Simone, Bowman, Robert L., Yarilin, Dmitry, Romin, Yevgeniy, Barlas, Afsar, Mulvey, J. Justin, Fujisawa, Sho, Xu, Ke, Ruggiero, Alessandro, Riabov, Vladimir, Thorek, Daniel L. J., Ulmert, Hans David S., Brea, Elliott J., Behling, Katja, Kzhyshkowska, Julia, Manova-Todorova, Katia, Scheinberg, David A., & McDevitt, Michael R. Deconvoluting hepatic processing of carbon nanotubes. United States. https://doi.org/10.1038/ncomms12343
Alidori, Simone, Bowman, Robert L., Yarilin, Dmitry, Romin, Yevgeniy, Barlas, Afsar, Mulvey, J. Justin, Fujisawa, Sho, Xu, Ke, Ruggiero, Alessandro, Riabov, Vladimir, Thorek, Daniel L. J., Ulmert, Hans David S., Brea, Elliott J., Behling, Katja, Kzhyshkowska, Julia, Manova-Todorova, Katia, Scheinberg, David A., and McDevitt, Michael R. Fri .
"Deconvoluting hepatic processing of carbon nanotubes". United States. https://doi.org/10.1038/ncomms12343. https://www.osti.gov/servlets/purl/1326670.
@article{osti_1326670,
title = {Deconvoluting hepatic processing of carbon nanotubes},
author = {Alidori, Simone and Bowman, Robert L. and Yarilin, Dmitry and Romin, Yevgeniy and Barlas, Afsar and Mulvey, J. Justin and Fujisawa, Sho and Xu, Ke and Ruggiero, Alessandro and Riabov, Vladimir and Thorek, Daniel L. J. and Ulmert, Hans David S. and Brea, Elliott J. and Behling, Katja and Kzhyshkowska, Julia and Manova-Todorova, Katia and Scheinberg, David A. and McDevitt, Michael R.},
abstractNote = {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. Lastly, the pharmacologic profile in cynomolgus monkeys is equivalent to what was reported in mice and suggests that nanotubes should behave similarly in humans.},
doi = {10.1038/ncomms12343},
journal = {Nature Communications},
number = ,
volume = 7,
place = {United States},
year = {Fri Jul 29 00:00:00 EDT 2016},
month = {Fri Jul 29 00:00:00 EDT 2016}
}
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journal, March 2010
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journal, November 2002
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Stabilin-1, a homeostatic scavenger receptor with multiple functions
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Targeted fibrillar nanocarbon RNAi treatment of acute kidney injury
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- Alidori, Simone; Akhavein, Nima; Thorek, Daniel L. J.
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A remarkable permeability of canalicular tight junctions might facilitate retrograde, non-viral gene delivery to the liver via the bile duct
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- Gut, Vol. 54, Issue 10
Targeting endothelial cells by gene therapy
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PET Imaging of Soluble Yttrium-86-Labeled Carbon Nanotubes in Mice
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- McDevitt, Michael R.; Chattopadhyay, Debjit; Jaggi, Jaspreet S.
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Fibrillous Carbon Nanotube: An Unexpected Journey
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- McDevitt, Michael R.; Scheinberg, David A.
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The Three-Dimensional Microanatomy of the Liver
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- Motta, Pietro M.
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text, January 2012
- N., Harris, Edward; Jian, Liu,; Sandhya, Gopalakrishnan,
- The University of North Carolina at Chapel Hill University Libraries
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journal, April 2008
- Lacerda, Lara; Ali-Boucetta, Hanene; Herrero, Maria A.
- Nanomedicine, Vol. 3, Issue 2
Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats
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- Longmire, Michelle; Choyke, Peter L.; Kobayashi, Hisataka
- Nanomedicine, Vol. 3, Issue 5
Distribution and clearance of PEG-single-walled carbon nanotube cancer drug delivery vehicles in mice
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Carbon Nanotubes: Potential Benefits and Risks of Nanotechnology in Nuclear Medicine
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The Dual Role of the Liver in Nanomedicine as an Actor in the Elimination of Nanostructures or a Therapeutic Target
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- Baboci, Lorena; Capolla, Sara; Di Cintio, Federica
- Journal of Oncology, Vol. 2020