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21 results on '"Guillaume Bort"'

1. Breaking photoswitch activation depth limit using ionising radiation stimuli adapted to clinical application

Author

Alban Guesdon-Vennerie, Patrick Couvreur, Fatoumia Ali, Frédéric Pouzoulet, Christophe Roulin, Immaculada Martínez-Rovira, Guillaume Bernadat, François-Xavier Legrand, Claudie Bourgaux, Cyril Lucien Mazars, Sergio Marco, Sylvain Trépout, Simona Mura, Sébastien Mériaux, and Guillaume Bort

Subjects
Science
Abstract

Triggered therapeutics are of interest but currently suffer from limited penetration depth of light sources. Here, the authors report on the development of a system, called radioswitch, that uses ionising irradiation to switch an azobenzene modified drug to an active form for deep tissue triggered therapeutic application.

Published
2022
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2. Conjugation of squalene to gemcitabine as unique approach exploiting endogenous lipoproteins for drug delivery

Author

Dunja Sobot, Simona Mura, Semen O. Yesylevskyy, Laura Dalbin, Fanny Cayre, Guillaume Bort, Julie Mougin, Didier Desmaële, Sinda Lepetre-Mouelhi, Grégory Pieters, Bohdan Andreiuk, Andrey S. Klymchenko, Jean-Louis Paul, Christophe Ramseyer, and Patrick Couvreur

Subjects
Science
Abstract

The interaction of nanoparticles with a range of biomolecules once they have been injected within the body can affect their performance. Here, the authors demonstrate that squalene nanomaterials conjugated with anticancer drugs can interact with lipoproteins and can be used to target cancer cells.

Published
2017
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3. Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI

Author

Francisco Perez-Balderas, Sander I. van Kasteren, Alaa A. A. Aljabali, Kim Wals, Sébastien Serres, Andrew Jefferson, Manuel Sarmiento Soto, Alexandre A. Khrapitchev, James R Larkin, Claire Bristow, Seung Seo Lee, Guillaume Bort, Filippo De Simone, Sandra J. Campbell, Robin P. Choudhury, Daniel C. Anthony, Nicola R. Sibson, and Benjamin G. Davis

Subjects
Science
Abstract

Iron oxide microparticles (MPIO) are better MRI contrast agents than nanoparticles, but are of limited clinical use as they are not degradable and so risk toxicity. Here the authors present an iron oxide microparticle MRI contrast agent with peptide linkers that enable degradation into non-toxic nanoparticlesin vivo.

Published
2017
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4. Quantifying nanotherapeutic penetration using a hydrogel-based microsystem as a new 3D

Author

Saba, Goodarzi, Audrey, Prunet, Fabien, Rossetti, Guillaume, Bort, Olivier, Tillement, Erika, Porcel, Sandrine, Lacombe, Ting-Di, Wu, Jean-Luc, Guerquin-Kern, Hélène, Delanoë-Ayari, François, Lux, and Charlotte, Rivière

Subjects
Microscopy, Confocal, Neoplasms, Spheroids, Cellular, Humans, Nanoparticles, Hydrogels
Abstract

The huge gap between 2D in vitro assays used for drug screening and the in vivo 3D physiological environment hampered reliable predictions for the route and accumulation of nanotherapeutics in vivo. For such nanotherapeutics, multi-cellular tumour spheroids (MCTS) are emerging as a good alternative in vitro model. However, the classical approaches to produce MCTS suffer from low yield, slow process, difficulties in MCTS manipulation and compatibility with high-magnification fluorescence optical microscopy. On the other hand, spheroid-on-chip set-ups developed so far require a practical knowledge of microfluidics difficult to transfer to a cell biology laboratory. We present here a simple yet highly flexible 3D model microsystem consisting of agarose-based microwells. Fully compatible with the multi-well plate format conventionally used in cell biology, our simple process enables the formation of hundreds of reproducible spheroids in a single pipetting. Immunostaining and fluorescence imaging including live high-resolution optical microscopy can be performed in situ, with no manipulation of spheroids. As a proof of principle of the relevance of such an in vitro platform for nanotherapeutic evaluation, this study investigates the kinetics and localisation of nanoparticles within colorectal cancer MCTS cells (HCT-116). The nanoparticles chosen are sub-5 nm ultrasmall nanoparticles made of polysiloxane and gadolinium chelates that can be visualized in MRI (AGuIX®, currently implicated in clinical trials as effective radiosensitizers for radiotherapy) and confocal microscopy after addition of Cy5.5. We show that the amount of AGuIX® nanoparticles within cells is largely different in 2D and 3D. Using our flexible agarose-based microsystems, we are able to resolve spatially and temporally the penetration and distribution of AGuIX® nanoparticles within MCTS. The nanoparticles are first found in both extracellular and intracellular space of MCTS. While the extracellular part is washed away after a few days, we evidenced intracellular localisation of AGuIX®, mainly within the lysosomal compartment, but also occasionally within mitochondria. Hence, our agarose-based microsystem appears as a promising 3D in vitro user-friendly platform for investigation of nanotherapeutic transport, ahead of in vivo studies.

Published
2021

5. Quantifying nanotherapeutic penetration using hydrogel based microsystem as a new 3D in vitro platform

Author

Olivier Tillement, Ting-Di Wu, Jean-Luc Guerquin-Kern, Sandrine Lacombe, Saba Goodarzi, Charlotte Rivière, Audrey Prunet, Hélène Delanoë-Ayari, Erika Porcel, Guillaume Bort, Fabien Rossetti, François Lux, Biophysique (BIOPHYSIQUE), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut des Sciences Moléculaires d'Orsay (ISMO), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon

Subjects
Fluorescence-lifetime imaging microscopy, Microfluidics, Biomedical Engineering, Bioengineering, 02 engineering and technology, Biochemistry, law.invention, 03 medical and health sciences, chemistry.chemical_compound, [SPI]Engineering Sciences [physics], In vivo, Confocal microscopy, law, Microsystem, [CHIM]Chemical Sciences, 030304 developmental biology, [PHYS]Physics [physics], 0303 health sciences, In vitro toxicology, Spheroid, General Chemistry, 021001 nanoscience & nanotechnology, chemistry, Agarose, 0210 nano-technology, Biomedical engineering
Abstract

International audience; Abstract The huge gap between 2D in vitro assays used for drug screening, and the in vivo 3D-physiological environment hampered reliable predictions for the route and accumulation of nanotherapeutics in vivo. For such nanotherapeutics, Multi-Cellular Tumour Spheroids (MCTS) is emerging as a good alternative in vitro model. However, the classical approaches to produce MCTS suffer from low yield, slow process, difficulties in MCTS manipulation and compatibility with high-magnification fluorescent optical microscopy. On the other hand, spheroid-on-chip set-ups developed so far require a microfluidic practical knowledge difficult to transfer to a cell biology laboratory. We present here a simple yet highly flexible 3D-model microsystem consisting of agarose-based microwells. Fully compatible with the multi-well plates format conventionally used in cell biology, our simple process enables the formation of hundreds of reproducible spheroids in a single pipetting. Immunostaining and fluorescent imaging including live high-resolution optical microscopy can be performed in-situ , with no manipulation of spheroids. As a proof-of-principle of the relevance of such in vitro platform for nanotherapeutics evaluation, this study investigates the kinetic and localization of nanoparticles within colorectal cancer MCTS cells (HCT-116). The nanoparticles chosen are sub-5 nm ultrasmall nanoparticles made of polysiloxane and gadolinium chelates that can be visualized in MRI (AGuIX ® , currently implicated in clinical trials as effective radiosensitizers for radiotherapy) and confocal microscopy after addition of Cy 5.5. We show that the amount of AGuIX ® nanoparticles within cells is largely different in 2D and 3D. Using our flexible agarose-based microsystems, we are able to resolve spatially and temporally the penetration and distribution of AGuIX ® nanoparticles within MCTS. The nanoparticles are first found in both extracellular and intracellular space of MCTS. While the extracellular part is washed away after few days, we evidenced intracellular localisation of AGuIX ® , mainly within lysosomes compartment, but also occasionally within mitochondria. Our agarose-based microsystem appears hence as a promising 3D in vitro user-friendly platform for investigation of nanotherapeutics transport, ahead of in vivo studies. Abstract Figure Graphical abstract

Published
2021

6. Correction: Quantifying nanotherapeutic penetration using a hydrogel-based microsystem as a new 3D in vitro platform

Author

Saba Goodarzi, Audrey Prunet, Fabien Rossetti, Guillaume Bort, Olivier Tillement, Erika Porcel, Sandrine Lacombe, Ting-Di Wu, Jean-Luc Guerquin-Kern, Hélène Delanoë-Ayari, François Lux, and Charlotte Rivière

Subjects
Biomedical Engineering, Bioengineering, General Chemistry, Biochemistry
Abstract

Correction for ‘Quantifying nanotherapeutic penetration using a hydrogel-based microsystem as a new 3D in vitro platform’ by Saba Goodarzi et al., Lab Chip, 2021, 21, 2495–2510, DOI: 10.1039/D1LC00192B.

Published
2022

7. AGuIX® from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine

Author

Camille Verry, Awatef Allouch, Carolyn J. Anderson, Olivier Tillement, Cyrus Chargari, Nathalie Mignet, Benoit Larrat, Marc Janier, Jacqueline Sidi-Boumedine, Kevin M. Prise, Peter Fries, Bich-Thuy Doan, Erika Porcel, Fabien Rossetti, Jacques Balosso, Marie-Caline Abadjian, Dominique Ardail, Frédéric Boschetti, Yannick Crémillieux, Alexandre Detappe, Claire Rodriguez-Lafrasse, Ross Berbeco, Marie-Thérèse Aloy, Sébastien Mériaux, Vu Long Tran, Emmanuel L. Barbier, Sandrine Lacombe, Sandrine Dufort, Matteo Martini, Andreas Müller, Eric Deutsch, Karl T. Butterworth, Emmanuelle Canet-Soulas, Géraldine Le Duc, Franck Denat, Goran Angelovski, Guillaume Bort, Céline Frochot, Jean-Luc Perfettini, Eloise Thomas, Stéphane Roux, Tristan Doussineau, Muriel Barberi-Heyob, Michael J. Evans, François Lux, Charles Truillet, Stephen J. McMahon, Penelope Bouziotis, Thomas, Noémie, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), NH TherAguix SA [Meylan], Nano-H SAS, Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CheMatech - Macrocycle Design Technologies, Max Planck Institute for Biological Cybernetics, Max-Planck-Gesellschaft, Dana-Farber Cancer Institute [Boston], Centre de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Université Paris sciences et lettres (PSL), Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Neuro-imagerie fonctionnelle et métabolique (ANTE-INSERM U836, équipe 5), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (UTINAM), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Clinic for Diagnostic and Interventional Radiology, Saarland University Medical Center, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Center for Scientific Research 'Demokritos' (NCSR), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Réactions et Génie des Procédés (LRGP), Rayonnement synchrotron et Recherche Médicale, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), University of California [San Francisco] (UC San Francisco), University of California (UC), Université de Lyon, Centre for Cancer Research and Cell Biology, Queen's University [Belfast] (QUB), PRISME (PRISME), Institut de Physique des 2 Infinis de Lyon (IP2I Lyon), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique Nucléaire de Lyon (IPNL), Institut des Sciences Moléculaires d'Orsay (ISMO), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Radiothérapie moléculaire (UMR 1030), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Curiethérapie, Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Gustave Roussy (IGR), Institut de Recherche Biomédicale des Armées (IRBA), French Military Health Service Academy, École du Val de Grâce (EVDG), Service de Santé des Armées-Service de Santé des Armées, Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), University of California [San Francisco] (UCSF), University of California, Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), NH Theraguix, Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Service Hospitalier Frédéric Joliot (SHFJ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Résonance magnétique des systèmes biologiques (RMSB), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), Paris Sciences et Lettres (PSL), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Equipe 6 : Rayonnement synchrotron et Recherche Médicale, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-[GIN] Grenoble Institut des Neurosciences, Université Paris-Sud 11 - Faculté de médecine (UP11 UFR Médecine), Ecole du Val-de-Grâce, UM Biochimie des Cancers et Biothérapies, CHU Grenoble-Institut de Biologie et Pathologie, Institut Européen des membranes (IEM), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS), Institut Galien Paris-Sud (IGPS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie et de Spectroscopie (LRMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de Mécanique et Technologie (LMT), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Institute of Computer Science VI, Université Henri Poincaré - Nancy 1 (UHP)-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS), Rhône-Alpes Research Program on Hadrontherapy, National French Hadrontherapy Centre - Etoile, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurorestoration Group, King‘s College London-Wolfson Centre for Age-related Diseases, Ciblage thérapeutique en Oncologie (EA3738), Unité Médicale d'Oncologie Moléculaire et Transfert (UMOMT), Hospices Civils de Lyon (HCL), Laboratoire des collisions atomiques et moléculaires (LCAM), Service d'oncologie-radiothérapie, Hôpital d'Instruction des Armées du Val de Grâce, Service de Santé des Armées, and European Synchrotron Radiation Facility (ESRF)

Subjects
Radiation-Sensitizing Agents, Gadolinium, medicine.medical_treatment, 02 engineering and technology, Review Article, Pharmacology, Theranostic Nanomedicine, Mice, 0302 clinical medicine, Melanoma, Brain Neoplasms, General Medicine, [CHIM.MATE]Chemical Sciences/Material chemistry, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 021001 nanoscience & nanotechnology, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Nuclear Medicine & Medical Imaging, Radiology Nuclear Medicine and imaging, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Toxicity, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 0210 nano-technology, Clinical Sciences, chemistry.chemical_element, [SDV.CAN]Life Sciences [q-bio]/Cancer, Enhanced permeability and retention effect, 03 medical and health sciences, SDG 3 - Good Health and Well-being, [SDV.CAN] Life Sciences [q-bio]/Cancer, In vivo, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, medicine, Animals, Humans, Radiology, Nuclear Medicine and imaging, [SDV.IB] Life Sciences [q-bio]/Bioengineering, business.industry, Cancer, medicine.disease, Radiation therapy, Clinical trial, chemistry, Nanoparticles, business, Forecasting
Abstract

International audience; AGuIX® are sub-5 nm nanoparticles made of a polysiloxane matrix and gadolinium chelates. This nanoparticle has been recently accepted in clinical trials in association with radiotherapy. This review will summarize the principal preclinical results that have led to first in man administration. No evidence of toxicity has been observed during regulatory toxicity tests on two animal species (rodents and monkeys). Biodistributions on different animal models have shown passive uptake in tumours due to enhanced permeability and retention effect combined with renal elimination of the nanoparticles after intravenous administration. High radiosensitizing effect has been observed with different types of irradiations in vitro and in vivo on a large number of cancer types (brain, lung, melanoma, head and neck…). The review concludes with the second generation of AGuIX nanoparticles and the first preliminary results on human.

Published
2019

8. Straightforward synthesis of PET tracer precursors used for the early diagnosis of Alzheimers disease through Suzuki–Miyaura cross-coupling reactions

Author

Maité Sylla-Iyarreta Veitía, Clotilde Ferroud, Guillaume Bort, Laboratoire de Chimie moléculaire, génie des procédés chimiques et énergétiques (CMGPCE), and Conservatoire National des Arts et Métiers [CNAM] (CNAM)

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, 010405 organic chemistry, Organic Chemistry, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [CHIM.CATA]Chemical Sciences/Catalysis, medicine.disease, 01 natural sciences, Biochemistry, Combinatorial chemistry, Coupling reaction, 0104 chemical sciences, 3. Good health, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, chemistry, Drug Discovery, medicine, Pet tracer, Alzheimer's disease, Pittsburgh compound B, 030217 neurology & neurosurgery
Abstract

In positron emission tomography [11C]PIB, Pittsburgh Compound-B, is currently the most widely used radiopharmaceutical for the early diagnosis of Alzheimer's disease. Synthetic routes for the preparation of the precursor of [11C]PIB are reported in the literature. These strategies require multiple steps and the use of protecting groups. This paper describes a simple one-step synthesis of the precursor of [11C]PIB through a Suzuki–Miyaura coupling reaction using thermal conditions or microwave activation. These methods were successfully applied to the synthesis of various 2-arylbenzothiazole and 2-pyridinylbenzothiazole compounds including [18F] precursor derivatives of PIB containing a nitro function.

Published
2013

9. Von Ein- zu Zwei-Photonen-Sonden: photoaktivierbare Reagentien, Aktuatoren und Photoschalter

Author

Guillaume Bort, Peter I. Dalko, Thibault Gallavardin, and David Ogden

Subjects
General Medicine
Abstract

Molekulare Systeme, die mit Licht “ferngesteuert” werden konnen, sind von wachsender Bedeutung in der Zellbiologie, der Physiologie und den Neurowissenschaften. Der entscheidende Aspekt hierbei ist die hohe raumliche und zeitliche Prazision, die mit Methoden der Lasermikroskopie erreicht werden kann. Das Verfahren der Zwei-Photonen-Anregung hat signifikante Vorzuge bei der Visualisierung biologischer Gewebe, allerdings ist der gezielte Entwurf intelligenter Sonden, die mit der Zellphysiologie kompatibel sind, nicht trivial. Dieser Aufsatz diskutiert die “chemischen” Herausforderungen bei der Entwicklung von Zwei-Photonen-Sonden.

Published
2013

10. OPTICAL IMAGING AND CHEMOTHERAPY

Author

Simona Mura, Patrick Couvreur, Guillaume Bort, Institut Galien Paris-Sud (IGPS), and Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)

Subjects
medicine.medical_specialty, Chemotherapy, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, business.industry, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.BA]Life Sciences [q-bio]/Animal biology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Optical imaging, [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, medicine, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [CHIM]Chemical Sciences, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Radiology, business, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2016

11. Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI

Author

Francisco, Perez-Balderas, Sander I, van Kasteren, Alaa A A, Aljabali, Kim, Wals, Sébastien, Serres, Andrew, Jefferson, Manuel, Sarmiento Soto, Alexandre A, Khrapitchev, James R, Larkin, Claire, Bristow, Seung Seo, Lee, Guillaume, Bort, Filippo, De Simone, Sandra J, Campbell, Robin P, Choudhury, Daniel C, Anthony, Nicola R, Sibson, and Benjamin G, Davis

Subjects
Male, Contrast Media, Vascular Cell Adhesion Molecule-1, Ferric Compounds, Magnetic Resonance Imaging, Antibodies, Article, Mice, RAW 264.7 Cells, Animals, Humans, Particle Size, Magnetite Nanoparticles, Peptide Hydrolases
Abstract

Ligand-conjugated microparticles of iron oxide (MPIO) have the potential to provide high sensitivity contrast for molecular magnetic resonance imaging (MRI). However, the accumulation and persistence of non-biodegradable micron-sized particles in liver and spleen precludes their clinical use and limits the translational potential of MPIO-based contrast agents. Here we show that ligand-targeted MPIO derived from multiple iron oxide nanoparticles may be coupled covalently through peptide linkers that are designed to be cleaved by intracellular macrophage proteases. The synthesized particles possess potential characteristics for targeted MRI contrast agents, including high relaxivity, unappreciable sedimentation, clearance from circulation and no overt toxicity. Importantly, we demonstrate that these particles are rapidly degraded both in vitro and in vivo, and that the targeted probes can be used for detection of inflammation in vivo using MRI. This approach provides a platform for molecular MRI contrast agents that is potentially more suitable for translation to humans., Iron oxide microparticles (MPIO) are better MRI contrast agents than nanoparticles, but are of limited clinical use as they are not degradable and so risk toxicity. Here the authors present an iron oxide microparticle MRI contrast agent with peptide linkers that enable degradation into non-toxic nanoparticles in vivo.

Published
2016

12. X-ray Photolysis To Release Ligands from Caged Reagents by an Intramolecular Antenna Sensitive to Magnetic Resonance Imaging

Author

Daniel Scherman, Morgane Petit, Clotilde Ferroud, David Ogden, Guillaume Bort, Bich-Thuy Doan, Peter I. Dalko, and Cécile Sicard

Subjects
Photolysis, Molecular Structure, medicine.diagnostic_test, X-Rays, Gadolinium, Photodissociation, X-ray, chemistry.chemical_element, Magnetic resonance imaging, General Medicine, General Chemistry, Ligands, Photochemistry, Magnetic Resonance Imaging, Catalysis, chemistry, Reagent, Intramolecular force, Radiolysis, Quinolines, medicine, Indicators and Reagents, Antenna (radio)
Published
2011

13. Gadolinium-Based Contrast Agents Targeted to Amyloid Aggregates for the Early Diagnosis of Alzheimer’s Disease by MRI

Author

Gaëlle Louin, Sébastien Ballet, Hélène Borderies, Marc Port, Clotilde Ferroud, Adel Kebsi, Guillaume Bort, Sarah Catoen, Laboratoire de transformations chimiques et pharmaceutiques (LTCP), Conservatoire National des Arts et Métiers [CNAM] (CNAM), and Laboratoire Guerbet

Subjects
Amyloid, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Gadolinium, [SDV]Life Sciences [q-bio], Contrast Media, chemistry.chemical_element, Plaque, Amyloid, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, 010402 general chemistry, 01 natural sciences, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Nuclear magnetic resonance, Alzheimer Disease, In vivo, Drug Discovery, medicine, Animals, Humans, DOTA, Chelation, Radionuclide Imaging, ComputingMilieux_MISCELLANEOUS, Pharmacology, medicine.diagnostic_test, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Magnetic resonance imaging, General Medicine, 3. Good health, 0104 chemical sciences, Early Diagnosis, chemistry, Positron emission tomography, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 030217 neurology & neurosurgery
Abstract

While important efforts were made in the development of positron emission tomography (PET) tracers for the in vivo molecular diagnosis of Alzheimer's disease, very few investigations to develop magnetic resonance imaging (MRI) probes were performed. Here, a new generation of Gd(III)-based contrast agents (CAs) is proposed to detect the amyloid β-protein (Aβ) aggregates by MRI, one of the earliest biological hallmarks of the pathology. A building block strategy was used to synthesize a library of 16 CAs to investigate structure-activity relationships (SARs) on physicochemical properties and binding affinity for the Aβ aggregates. Three types of blocks were used to modulate the CA structures: (i) the Gd(III) chelates (Gd(III)-DOTA and Gd(III)-PCTA), (ii) the biovectors (2-arylbenzothiazole, 2-arylbenzoxazole and stilbene derivatives) and (iii) the linkers (neutrals, positives and negatives with several lengths). These investigations revealed unexpected SARs and a difficulty of these probes to cross the blood-brain barrier (BBB). General insights for the development of Gd(III)-based CAs to detect the Aβ aggregates are described.

Published
2014

14. ChemInform Abstract: Straightforward Synthesis of PET Tracer Precursors Used for the Early Diagnosis of Alzheimers Disease Through Suzuki-Miyaura Cross-Coupling Reactions

Author

Guillaume Bort, Clotilde Ferroud, and Maité Sylla-Iyarreta Veitía

Subjects
Computational chemistry, Chemistry, Organic chemistry, General Medicine, Pet tracer, Coupling reaction
Abstract

A simple one-step synthesis of a Pittsburgh compound-B (PiB) precursor through Suzuki—Miyaura cross-coupling reaction using thermal conditions or microwave activation is described.

Published
2013

15. ChemInform Abstract: From One-Photon to Two-Photon Probes: 'Caged' Compounds, Actuators, and Photoswitches

Author

Peter I. Dalko, Guillaume Bort, David Ogden, and Thibault Gallavardin

Subjects
Cell physiology, Laser Microscopy, Photon, Two-photon excitation microscopy, Chemistry, Nanotechnology, General Medicine, Molecular systems, Actuator, Excitation
Abstract

Molecular systems that can be remotely controlled by light are gaining increasing importance in cell biology, physiology, and neurosciences because of the spatial and temporal precision that is achievable with laser microscopy. Two-photon excitation has significant advantages deep in biological tissues, but raises problems in the design of "smart" probes compatible with cell physiology. This Review discusses the chemical challenges in generating suitable two-photon probes.

Published
2013

16. From One-Photon to Two-Photon Probes: 'Caged' Compounds, Actuators, and Photoswitches

Author

Peter I. Dalko, Guillaume Bort, David Ogden, Thibault Gallavardin, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiologie cérébrale (LPC - UMR 8118), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Gallavardin, Thibault

Subjects
Laser Microscopy, Macrocyclic Compounds, Photon, Nanotechnology, Molecular systems, 010402 general chemistry, 01 natural sciences, Catalysis, Cell Physiological Phenomena, Absorptiometry, Photon, Two-photon excitation microscopy, [CHIM] Chemical Sciences, cell signaling, [CHIM]Chemical Sciences, Nitrobenzenes, Chelating Agents, Photons, photochemistry, 010405 organic chemistry, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, General Chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Photochemical Processes, 0104 chemical sciences, caged compounds, protecting groups, Actuator, signal transduction
Abstract

International audience; Molecular systems that can be remotely controlled by light are gaining increasing importance in cell biology, physiology, and neurosciences because of the spatial and temporal precision that is achievable with laser microscopy. Two‐photon excitation has significant advantages deep in biological tissues, but raises problems in the design of “smart” probes compatible with cell physiology. This Review discusses the chemical challenges in generating suitable two‐photon probes.

Published
2013

17. Automated radiosynthesis of the Pittsburg compound-B using a commercial synthesizer

Author

Mathieu Verdurand, Vincent Tadino, Didier Le Bars, Luc Zimmer, Frédéric Bonnefoi, and Guillaume Bort

Subjects
Methyl triflate, Aniline Compounds, medicine.diagnostic_test, Chemistry, Radiochemistry, General Medicine, Automated radiosynthesis, Thiazoles, Fully automated, Positron emission tomography, medicine, Radiology, Nuclear Medicine and imaging, Benzothiazoles, Carbon Radioisotopes, Radiopharmaceuticals
Abstract

Background The Pittsburgh compound-B ([11C]PIB) is a highly interesting radiotracer for imaging amyloid plaques in Alzheimer's disease by positron emission tomography (PET). An increasing number of PET centres schedule its transfer for clinical studies and therefore are interested in its automated synthesis. Method With the aim of flexibility, we reported the first fully automated synthesis of [11C]PIB with the coupling of two commercial synthesizers. Results [11C]PIB was prepared from 2-(4'-aminophenyl)-6-hydroxybenzothiazole by [11C]methyl triflate methylation reacting in an high-performance liquid chromatography loop and resulting in a total radiochemical yield of 13+/-15% after a synthesis time of 25 min. The specific activity of [11C]PIB was 20-60 GBq/micromol and its radiochemical purity is more than 99%. Conclusion The rapid synthesis and the automatic auto-cleaning procedure allow convenient and reproducible [11C]PIB synthesis to be performed during the same day for preclinical or clinical PET scans.

Published
2008

18. Inside Cover: X-ray Photolysis To Release Ligands from Caged Reagents by an Intramolecular Antenna Sensitive to Magnetic Resonance Imaging (Angew. Chem. Int. Ed. 41/2011)

Author

Guillaume Bort, Peter I. Dalko, Morgane Petit, Bich-Thuy Doan, David Ogden, Cécile Sicard, Daniel Scherman, and Clotilde Ferroud

Subjects
chemistry, Gadolinium, Intramolecular force, Reagent, Photodissociation, Radiolysis, X-ray, chemistry.chemical_element, General Chemistry, Antenna (radio), Photochemistry, Catalysis
Published
2011

19. Innentitelbild: X-ray Photolysis To Release Ligands from Caged Reagents by an Intramolecular Antenna Sensitive to Magnetic Resonance Imaging (Angew. Chem. 41/2011)

Author

Bich-Thuy Doan, Cécile Sicard, Daniel Scherman, Morgane Petit, Clotilde Ferroud, David Ogden, Peter I. Dalko, and Guillaume Bort

Subjects
medicine.diagnostic_test, Chemistry, Reagent, Intramolecular force, Photodissociation, X-ray, medicine, Analytical chemistry, Magnetic resonance imaging, General Medicine, Antenna (radio), Photochemistry
Published
2011

20. Evaluation of the simultaneous use of standard additions and internal standards calibration techniques for inductively coupled plasma mass spectrometry

Author

Guillaume Bort, Eric D. Salin, and Margaret Antler

Subjects
Matrix (chemical analysis), Nickel, chemistry, Molybdenum, Standard addition, Calibration, Analytical chemistry, chemistry.chemical_element, Thallium, Yttrium, Inductively coupled plasma mass spectrometry, Spectroscopy, Analytical Chemistry
Abstract

The use of internal standards combined with standard additions calibration for inductively coupled plasma mass spectrometry (ICP-MS) is discussed. Yttrium, rhodium, magnesium, cobalt, copper, nickel, silver, thallium, molybdenum and lead were analyzed in solutions of known composition with a 500 mg ml−1 Na matrix. Additionally, the Mg, Co, Y, Rh and Pb signals were used as internal standards for the other elements in the same matrix. Severe drift effects were simulated by drastically altering the liquid sample uptake rate. The signals were used to compare the results obtained using four different calibration methods: external standards, standard additions, internal standards and standard additions in combination with an internal standard. The average errors for external standards varied from 23 to 41% while the average errors for internal standards ranged from 1 to 71%. The error for standard additions was 45%. The use of standard additions with an internal standard produced an average error of 0.7–5%, suggesting that this is a powerful calibration technique.

Published
2004

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