title: Minor changes in the macrocyclic ligands but major consequences on the efficiency of gold nanoparticles designed for radiosensitization.
abstract: Many studies have been devoted to adapting the design of gold nanoparticles to efficiently exploit their promising capability to enhance the effects of radiotherapy. In particular, the addition of magnetic resonance imaging modality constitutes an attractive strategy for enhancing the selectivity of radiotherapy since it allows the determination of the most suited delay between the injection of nanoparticles and irradiation. This requires the functionalization of the gold core by an organic shell composed of thiolated gadolinium chelates. The risk of nephrogenic systemic fibrosis induced by the release of gadolinium ions should encourage the use of macrocyclic chelators which form highly stable and inert complexes with gadolinium ions. In this context, three types of gold nanoparticles (Au@DTDOTA, Au@TADOTA and Au@TADOTAGA) combining MRI, nuclear imaging and radiosensitization have been developed with different macrocyclic ligands anchored onto the gold cores. Despite similarities in size and organic shell composition, the distribution of gadolinium chelate-coated gold nanoparticles (Au@TADOTA-Gd and Au@TADOTAGA-Gd) in the tumor zone is clearly different. As a result, the intravenous injection of Au@TADOTAGA-Gd prior to the irradiation of 9L gliosarcoma bearing rats leads to the highest increase in lifespan whereas the radiophysical effects of Au@TADOTAGA-Gd and Au@TADOTA-Gd are very similar.
authors.affiliation: Institut UTINAM, UMR 6213 CNRS-UBFC, Université de Bourgogne Franche-Comté, 25030 Besançon Cedex, France. stephane.roux@univ-fcomte.fr.
authors.forename: G
authors.initials: G
authors.lastname: Laurent
authors.affiliation: Institut de Chimie Moléculaire de l'Université de Bourgogne (ICMUB), UMR 6302 CNRS-UBFC, Université de Bourgogne Franche-Comté, 21078 Dijon Cedex, France.
authors.forename: C
authors.initials: C
authors.lastname: Bernhard
authors.affiliation: Nano-H S.A.S, 2 Place de l'Europe, 38070 Saint Quentin-Fallavier, France.
authors.forename: S
authors.initials: S
authors.lastname: Dufort
authors.affiliation: Institut UTINAM, UMR 6213 CNRS-UBFC, Université de Bourgogne Franche-Comté, 25030 Besançon Cedex, France. stephane.roux@univ-fcomte.fr.
authors.forename: G
authors.initials: G
authors.lastname: Jiménez Sánchez
authors.affiliation: Institut UTINAM, UMR 6213 CNRS-UBFC, Université de Bourgogne Franche-Comté, 25030 Besançon Cedex, France. stephane.roux@univ-fcomte.fr.
authors.forename: R
authors.initials: R
authors.lastname: Bazzi
authors.affiliation: CheMatech S.A.S., 21000 Dijon, France.
authors.forename: F
authors.initials: F
authors.lastname: Boschetti
authors.affiliation: Institut de Chimie Moléculaire de l'Université de Bourgogne (ICMUB), UMR 6302 CNRS-UBFC, Université de Bourgogne Franche-Comté, 21078 Dijon Cedex, France.
authors.forename: M
authors.initials: M
authors.lastname: Moreau
authors.affiliation: Institut de Chimie Moléculaire de l'Université de Bourgogne (ICMUB), UMR 6302 CNRS-UBFC, Université de Bourgogne Franche-Comté, 21078 Dijon Cedex, France.
authors.forename: T H
authors.initials: TH
authors.lastname: Vu
authors.affiliation: Institut de Chimie Moléculaire de l'Université de Bourgogne (ICMUB), UMR 6302 CNRS-UBFC, Université de Bourgogne Franche-Comté, 21078 Dijon Cedex, France and Plateforme d'imagerie préclinique, Centre Georges-François Leclerc, 21079 Dijon Cedex, France.
authors.forename: B
authors.initials: B
authors.lastname: Collin
authors.affiliation: Plateforme d'imagerie préclinique, Centre Georges-François Leclerc, 21079 Dijon Cedex, France.
authors.forename: A
authors.initials: A
authors.lastname: Oudot
authors.affiliation: Recombinaison, réparation et cancer: de la molécule au patient, Institut Curie, UMR CNRS 3347 - Inserm U1021, 91405 Orsay, France.
authors.forename: N
authors.initials: N
authors.lastname: Herath
authors.affiliation: ID17 Biomedical Beamline, European Synchrotron Radiation Facility, 38000 Grenoble, France.
authors.forename: H
authors.initials: H
authors.lastname: Requardt
authors.affiliation: NMR Laboratory, Université de Mons, 7000 Mons, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Laurent
authors.affiliation: NMR Laboratory, Université de Mons, 7000 Mons, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Vander Elst
authors.affiliation: NMR Laboratory, Université de Mons, 7000 Mons, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Muller
authors.affiliation: Recombinaison, réparation et cancer: de la molécule au patient, Institut Curie, UMR CNRS 3347 - Inserm U1021, 91405 Orsay, France.
authors.forename: M
authors.initials: M
authors.lastname: Dutreix
authors.affiliation: Institut de Chimie Moléculaire de l'Université de Bourgogne (ICMUB), UMR 6302 CNRS-UBFC, Université de Bourgogne Franche-Comté, 21078 Dijon Cedex, France.
authors.forename: M
authors.initials: M
authors.lastname: Meyer
authors.affiliation: Plateforme d'imagerie préclinique, Centre Georges-François Leclerc, 21079 Dijon Cedex, France.
authors.forename: F
authors.initials: F
authors.lastname: Brunotte
authors.affiliation: Matériaux Ingénierie et Science, UMR 5510 CNRS-INSA, INSA de Lyon, 69621 Villeurbanne Cedex, France.
authors.forename: P
authors.initials: P
authors.lastname: Perriat
authors.affiliation: Institut Lumière Matière, UMR 5306 CNRS-UCBL, Université de Lyon, 69622 Villeurbanne Cedex, France.
authors.forename: F
authors.initials: F
authors.lastname: Lux
authors.affiliation: Institut Lumière Matière, UMR 5306 CNRS-UCBL, Université de Lyon, 69622 Villeurbanne Cedex, France.
authors.forename: O
authors.initials: O
authors.lastname: Tillement
authors.affiliation: ID17 Biomedical Beamline, European Synchrotron Radiation Facility, 38000 Grenoble, France.
authors.forename: G
authors.initials: G
authors.lastname: Le Duc
authors.affiliation: Institut de Chimie Moléculaire de l'Université de Bourgogne (ICMUB), UMR 6302 CNRS-UBFC, Université de Bourgogne Franche-Comté, 21078 Dijon Cedex, France.
authors.forename: F
authors.initials: F
authors.lastname: Denat
authors.affiliation: Institut UTINAM, UMR 6213 CNRS-UBFC, Université de Bourgogne Franche-Comté, 25030 Besançon Cedex, France. stephane.roux@univ-fcomte.fr.
authors.forename: S
authors.initials: S
authors.lastname: Roux