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Title: Carbon nanotubes exhibit fibrillar pharmacology in primates

Nanomedicine rests at the nexus of medicine, bioengineering, and biology with great potential for improving health through innovation and development of new drugs and devices. Carbon nanotubes are an example of a fibrillar nanomaterial poised to translate into medical practice. The leading candidate material in this class is ammonium-functionalized carbon nanotubes (fCNT) that exhibits unexpected pharmacological behavior in vivo with important biotechnology applications. Here, we provide a multi-organ evaluation of the distribution, uptake and processing of fCNT in nonhuman primates using quantitative whole body positron emission tomography (PET), compartmental modeling of pharmacokinetic data, serum biomarkers and ex vivo pathology investigation. Kidney and liver are the two major organ systems that accumulate and excrete [ 86Y]fCNT in nonhuman primates and accumulation is cell specific as described by compartmental modeling analyses of the quantitative PET data. A serial two-compartment model explains renal processing of tracer-labeled fCNT; hepatic data fits a parallel two-compartment model. These modeling data also reveal significant elimination of the injected activity (>99.8%) from the primate within 3 days (t 1/2 = 11.9 hours). Thus, these favorable results in nonhuman primates provide important insight to the fate of fCNT in vivo and pave the way to further engineering design considerationsmore » for sophisticated nanomedicines to aid late stage development and clinical use in man.« less
Authors:
 [1] ;  [2] ;  [3] ;  [1] ;  [1] ;  [4] ;  [5] ; ORCiD logo [6]
  1. Memorial Sloan Kettering Cancer Center, New York City, NY (United States). Dept. of Radiology
  2. Johns Hopkins Univ., Baltimore, MD (United States). Dept. of Radiology and Radiological Sciences
  3. Memorial Sloan Kettering Cancer Center, New York City, NY (United States). Dept. of Medical Physics
  4. Memorial Sloan Kettering Cancer Center, Rockefeller Univ., Weill Cornell Medicine, New York City, NY (United States). Tri-Institutional Lab. of Comparative Pathology
  5. Memorial Sloan Kettering Cancer Center, New York City, NY (United States). Molecular Pharmacology Program; Weill Cornell Medicine, New York City, NY (United States). Dept. of Pharmacology and Dept. of Medicine
  6. Memorial Sloan Kettering Cancer Center, New York City, NY (United States). Dept. of Radiology; Weill Cornell Medicine, New York City, NY (United States). Dept. of Radiology
Publication Date:
Grant/Contract Number:
SC0002456; GM07739; R21 CA128406; R01 CA166078; R01 CA55349; R25T CA046945; R24 CA83084; P30 CA008748; P01 CA33049; F31 CA167863
Type:
Published Article
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 12; Journal Issue: 8; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Research Org:
Memorial Sloan Kettering Cancer Center, New York City, NY (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); Cornell Univ., Ithaca, NY (United States); City Univ. (CUNY), NY (United States); National Institutes of Health (NIH)
Country of Publication:
United States
Language:
English
Subject:
77 NANOSCIENCE AND NANOTECHNOLOGY; 62 RADIOLOGY AND NUCLEAR MEDICINE; 59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
1377131
Alternate Identifier(s):
OSTI ID: 1430211

Alidori, Simone, Thorek, Daniel L. J., Beattie, Bradley J., Ulmert, David, Almeida, Bryan Aristega, Monette, Sebastien, Scheinberg, David A., and McDevitt, Michael R.. Carbon nanotubes exhibit fibrillar pharmacology in primates. United States: N. p., Web. doi:10.1371/journal.pone.0183902.
Alidori, Simone, Thorek, Daniel L. J., Beattie, Bradley J., Ulmert, David, Almeida, Bryan Aristega, Monette, Sebastien, Scheinberg, David A., & McDevitt, Michael R.. Carbon nanotubes exhibit fibrillar pharmacology in primates. United States. doi:10.1371/journal.pone.0183902.
Alidori, Simone, Thorek, Daniel L. J., Beattie, Bradley J., Ulmert, David, Almeida, Bryan Aristega, Monette, Sebastien, Scheinberg, David A., and McDevitt, Michael R.. 2017. "Carbon nanotubes exhibit fibrillar pharmacology in primates". United States. doi:10.1371/journal.pone.0183902.
@article{osti_1377131,
title = {Carbon nanotubes exhibit fibrillar pharmacology in primates},
author = {Alidori, Simone and Thorek, Daniel L. J. and Beattie, Bradley J. and Ulmert, David and Almeida, Bryan Aristega and Monette, Sebastien and Scheinberg, David A. and McDevitt, Michael R.},
abstractNote = {Nanomedicine rests at the nexus of medicine, bioengineering, and biology with great potential for improving health through innovation and development of new drugs and devices. Carbon nanotubes are an example of a fibrillar nanomaterial poised to translate into medical practice. The leading candidate material in this class is ammonium-functionalized carbon nanotubes (fCNT) that exhibits unexpected pharmacological behavior in vivo with important biotechnology applications. Here, we provide a multi-organ evaluation of the distribution, uptake and processing of fCNT in nonhuman primates using quantitative whole body positron emission tomography (PET), compartmental modeling of pharmacokinetic data, serum biomarkers and ex vivo pathology investigation. Kidney and liver are the two major organ systems that accumulate and excrete [86Y]fCNT in nonhuman primates and accumulation is cell specific as described by compartmental modeling analyses of the quantitative PET data. A serial two-compartment model explains renal processing of tracer-labeled fCNT; hepatic data fits a parallel two-compartment model. These modeling data also reveal significant elimination of the injected activity (>99.8%) from the primate within 3 days (t1/2 = 11.9 hours). Thus, these favorable results in nonhuman primates provide important insight to the fate of fCNT in vivo and pave the way to further engineering design considerations for sophisticated nanomedicines to aid late stage development and clinical use in man.},
doi = {10.1371/journal.pone.0183902},
journal = {PLoS ONE},
number = 8,
volume = 12,
place = {United States},
year = {2017},
month = {8}
}