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The relationship between the diameter of chemically-functionalized multi-walled carbon nanotubes and their organ biodistribution profiles in vivo
Authors:Julie T-W. Wang,Chiara Fabbro,Enrica Venturelli,Cé  cilia Mé  nard-Moyon,Olivier Chaloin,Tatiana Da Ros,Laura Methven,Antonio Nunes,Jane K. Sosabowski,Stephen J. Mather,Martyn K. Robinson,Julien Amadou,Maurizio Prato,Alberto Bianco,Kostas Kostarelos,Khuloud T. Al-Jamal
Affiliation:1. Nanomedicine Laboratory, Centre for Drug Delivery Research, UCL-School of Pharmacy, University College London, London WC1N 1AX, UK;2. Institute of Pharmaceutical Science, King''s College London, London SE1 9NH, UK;3. Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Trieste, Trieste 34127, Italy;4. Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca''Foscari di Venezia, Venezia 30123, Italy;5. CNRS, Institut de Biologie Moléculaire et Cellulaire, Laboratoire d''Immunopathologie et Chimie Thérapeutique, Strasbourg F-67000, France;6. Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK;g UCB Celltech, Slough, Berkshire SL1 3WE, UK;h Nanocyl SA, Sambreville B-5060, Belgium
Abstract:
Carbon nanotubes (CNTs) exhibit unique properties which have led to their applications in the biomedical field as novel delivery systems for diagnosis and therapy purposes. We have previously reported that the degree of functionalization of CNTs is a key factor determining their biological behaviour. The present study broadens the spectrum by investigating the impact of the diameter of CNTs using two series of multi-walled CNTs (MWNTs) with distinct differences in their diameters. Both MWNTs were doubly functionalized by 1,3-dipolar cycloaddition and amidation reactions, allowing the appended functional groups to be further conjugated with radionuclide chelating moieties and antibodies or antibody fragments. All constructs possessed comparable degree of functionalization and were characterized by thermogravimetric analysis, transmission electron microscopy, gel electrophoresis and surface plasmon resonance. The MWNT conjugates were radio-labelled with indium-111, which thereby enabled in vivo single photon emission computed tomography/computed tomography (SPECT/CT) imaging and organ biodistribution study using γ-scintigraphy. The narrow MWNTs (average diameter: 9.2 nm) demonstrated enhanced tissue affinity including non-reticular endothelial tissues compared to the wider MWNTs (average diameter: 39.5 nm). The results indicate that the higher aspect ratio of narrow MWNTs may be beneficial for their future biological applications due to higher tissue accumulation.
Keywords:Carbon nanotubes   Functionalization   SPECT/CT   Organ biodistribution
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