title: The relationship between the diameter of chemically-functionalized multi-walled carbon nanotubes and their organ biodistribution profiles in vivo.
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.
authors.affiliation: Nanomedicine Laboratory, Centre for Drug Delivery Research, UCL-School of Pharmacy, University College London, London WC1N 1AX, UK; Institute of Pharmaceutical Science, King's College London, London SE1 9NH, UK.
authors.forename: Julie T-W
authors.initials: JT
authors.lastname: Wang
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Trieste, Trieste 34127, Italy; Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca'Foscari di Venezia, Venezia 30123, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fabbro
authors.affiliation: CNRS, Institut de Biologie Moléculaire et Cellulaire, Laboratoire d'Immunopathologie et Chimie Thérapeutique, Strasbourg F-67000, France.
authors.forename: Enrica
authors.initials: E
authors.lastname: Venturelli
authors.affiliation: CNRS, Institut de Biologie Moléculaire et Cellulaire, Laboratoire d'Immunopathologie et Chimie Thérapeutique, Strasbourg F-67000, France.
authors.forename: Cécilia
authors.initials: C
authors.lastname: Ménard-Moyon
authors.affiliation: CNRS, Institut de Biologie Moléculaire et Cellulaire, Laboratoire d'Immunopathologie et Chimie Thérapeutique, Strasbourg F-67000, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Chaloin
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Trieste, Trieste 34127, Italy.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Da Ros
authors.affiliation: Nanomedicine Laboratory, Centre for Drug Delivery Research, UCL-School of Pharmacy, University College London, London WC1N 1AX, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Methven
authors.affiliation: Nanomedicine Laboratory, Centre for Drug Delivery Research, UCL-School of Pharmacy, University College London, London WC1N 1AX, UK.
authors.forename: Antonio
authors.initials: A
authors.lastname: Nunes
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK.
authors.forename: Jane K
authors.initials: JK
authors.lastname: Sosabowski
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Mather
authors.affiliation: UCB Celltech, Slough, Berkshire SL1 3WE, UK.
authors.forename: Martyn K
authors.initials: MK
authors.lastname: Robinson
authors.affiliation: Nanocyl SA, Sambreville B-5060, Belgium.
authors.forename: Julien
authors.initials: J
authors.lastname: Amadou
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Trieste, Trieste 34127, Italy. Electronic address: prato@units.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Prato
authors.affiliation: Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca'Foscari di Venezia, Venezia 30123, Italy. Electronic address: a.bianco@ibmc-cnrs.unistra.fr.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bianco
authors.affiliation: Nanomedicine Laboratory, Centre for Drug Delivery Research, UCL-School of Pharmacy, University College London, London WC1N 1AX, UK. Electronic address: kostas.kostarelos@manchester.ac.uk.
authors.forename: Kostas
authors.initials: K
authors.lastname: Kostarelos
authors.affiliation: Nanomedicine Laboratory, Centre for Drug Delivery Research, UCL-School of Pharmacy, University College London, London WC1N 1AX, UK; Institute of Pharmaceutical Science, King's College London, London SE1 9NH, UK. Electronic address: khuloud.al-jamal@kcl.ac.uk.
authors.forename: Khuloud T
authors.initials: KT
authors.lastname: Al-Jamal
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging / Q000379:methods; D016503:Drug Delivery Systems; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon / Q000737:chemistry*; D010316:Particle Size; D020349:Surface Plasmon Resonance; D014018:Tissue Distribution
chemical_list: D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D037742:Nanotubes, Carbon
keywords: Carbon nanotubes; Functionalization; Organ biodistribution; SPECT/CT