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33 results on '"Bich-Thuy Doan"'

1. Doxorubicin (DOX) Gadolinium–Gold-Complex: A New Way to Tune Hybrid Nanorods as Theranostic Agent

Author

Memona Khan, Celia Arib, Nadia Djaker, Amadou Thierno Diallo, Jolanda Spadavecchia, Bich-Thuy Doan, Sarah Boumati, Chimie, Structures et Propriétés de Biomatériaux et d'Agents Thérapeutiques (CSPBAT), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Sorbonne Paris Nord

Subjects
Gadolinium, [SDV]Life Sciences [q-bio], Pharmaceutical Science, Nanoparticle, 02 engineering and technology, 01 natural sciences, Theranostic Nanomedicine, Mice, International Journal of Nanomedicine, Neoplasms, Drug Discovery, ComputingMilieux_MISCELLANEOUS, Original Research, Antibiotics, Antineoplastic, Nanotubes, Cell Death, General Medicine, 021001 nanoscience & nanotechnology, hyperthermia, Magnetic Resonance Imaging, Endocytosis, Nanorod, 0210 nano-technology, medicine.drug, MRI, hybrid nanorods, Biocompatibility, Photothermal Therapy, Biophysics, chemistry.chemical_element, Bioengineering, Conjugated system, 010402 general chemistry, doxorubicin, Biomaterials, Inhibitory Concentration 50, Cell Line, Tumor, medicine, [CHIM]Chemical Sciences, Animals, Humans, Chelation, Doxorubicin, Organic Chemistry, Photothermal therapy, Combinatorial chemistry, 0104 chemical sciences, MIAPaCa-2 cells, Drug Liberation, chemistry, Spectrophotometry, Ultraviolet, Gold
Abstract

Memona Khan,1 Sarah Boumati,2 Celia Arib,1 Amadou Thierno Diallo,1 Nadia Djaker,1 Bich-thuy Doan,2 Jolanda Spadavecchia1 1CNRS, UMR 7244, CSPBAT, Laboratoire de Chimie, Structures et Propriétés de Biomatériaux et d’Agents Thérapeutiques, Université Sorbonne Paris Nord, Bobigny, 93000, France; 2CNRS UMR 8060, iCLeHS, Synthèse, Electrochimie, Imagerie et Systèmes Analytiques Pour le Diagnostic SEISAD, Chimie ParisTech, Université PSL, Paris, 75231, FranceCorrespondence: Bich-thuy DoanCNRS, UMR 8060, iCLeHS, Synthèse, Electrochimie, Imagerie et Systèmes Analytiques Pour le Diagnostic SEISAD, Chimie ParisTech, PSL University, 11 Rue Pierre et Marie Curie, Paris Cedex 05, Paris, 75231, FranceEmail bich-thuy.doan@chimieparistech.psl.euJolanda SpadavecchiaCNRS, UMR 7244, CSPBAT, Laboratoire de Chimie, Structures et Propriétés de Biomatériaux et d’Agents Thérapeutiques, Sorbonne Paris Nord University, 1 rue chablis, Bobigny, 93000, FranceEmail jolanda.spadavecchia@gmail.comIntroduction: In this paper, we have designed and formulated, a novel synthesis of doxorubicin (DOX) loaded bimetallic gold nanorods in which gold salt (HAuCl4) is chelated with anthracycline (DOX), diacid polyethylene-glycol (PEG-COOH) and gadolinium salt (GdCl3 * 6 H2O) to form DOX IN-Gd-AuNRs compared with DOX ON-Gd-AuNRs in which the drug was grafted onto the bimetallic pegylated nanoparticle surface by electrostatic adsorption.Material and Method: The physical and chemical evaluation was performed by spectroscopic analytical techniques (Raman spectroscopy, UV-Visible and transmission electron microscopy (TEM)). Magnetic features at 7T were also measured. Photothermal abilities were assessed. Cytotoxicity studies on MIA PaCa-2, human pancreatic carcinoma and TIB-75 hepatocytes cell lines were carried out to evaluate their biocompatibility and showed a 320 fold higher efficiency for DOX after encapsulation.Results: Exhaustive physicochemical characterization studies were conducted showing a mid size of 20 to 40 nm diameters obtained with low polydispersity, efficient synthesis using seed mediated synthesis with chelation reaction with high scale-up, long duration stability, specific doxorubicin release with acidic pH, strong photothermal abilities at 808 nm in the NIR transparency window, strong magnetic r1 relaxivities for positive MRI, well adapted for image guided therapy and therapeutical purpose in biological tissues.Conclusion: In this paper, we have developed a novel theranostic nanoparticle composed of gadolinium complexes to gold ions, with a PEG biopolymer matrix conjugated with antitumoral doxorubicin, providing multifunctional therapeutic features. Particularly, these nano conjugates enhanced the cytotoxicity toward tumoral MIAPaCa-2 cells by a factor of 320 compared to doxorubicin alone. Moreover, MRI T1 features at 7T enables interesting positive contrast for bioimaging and their adapted size for potential passive targeting to tumors by Enhanced Permeability Retention. Given these encouraging antitumoral and imaging properties, this bimetallic theranostic nanomaterial system represents a veritable promise as a therapeutic entity in the field of medicinal applications.Keywords: hybrid nanorods, doxorubicin, MRI, MIAPaCa-2 cells, hyperthermia

Published
2021

2. Properties and bioeffects of magneto–near infrared nanoparticles on cancer diagnosis and treatment

Author

Thi My Nhung Hoang, Ke Son Phan, Thi Dieu Thuy Ung, Hai Doan Do, Hong Nam Pham, Thuc Quang Bui, Phuong Thu Ha, Thi Thu Trang Mai, Bich Thuy Doan, and Thi Thu Huong Le

Subjects
Biocompatibility, Chemistry, Spheroid, Nanoparticle, General Chemistry, Catalysis, Quantum dot, Drug delivery, Materials Chemistry, Zeta potential, medicine, Doxorubicin, Biomedical engineering, Superparamagnetism, medicine.drug
Abstract

In this study, a multifunctional drug delivery nanosystem Fe3O4–CdTe–alginate (FAQ) was prepared by coating Fe3O4 nanoparticles and CdTe quantum dots (QDs) simultaneously with alginate. High luminescent CdTe QDs can help label the cells for diagnostics while the superparamagnetic Fe3O4 component endows the abilities of hyperthermia and magnetic targeting to the system for cancer treatment. Besides, polymeric alginate provides biocompatibility and high stability (Zeta potential of −49.1 mV) and makes it possible to encapsulate cancer drug Doxorubicin (Dox) in the system. The fluorescence spectra of blank FAQ and FAQ loading Dox (FAQD) were analysed and compared to those of pure CdTe or Dox to confirm the formation of the nanosystems. Next, the samples were applied to in vitro treatment with several human cell lines (Hep-G2, LU-1, RD and Vero cell lines) and showed positive results with low IC50 values for these cells and exhibited higher impact of apoptosis induction and MCF7 spheroid growth delay compared to pure Dox. In particular, FAQ and FAQD have high values of r2 and show contrast increment in the MRI images. The results indicate that FAQ and FAQD can serve as excellent candidates for both cancer therapy and diagnostics.

Published
2020

3. Synthesis, Characterization and Evaluation of Peptide Nanostructures for Biomedical Applications

Author

Fanny d’Orlyé, Anne Varenne, Bich-Thuy Doan, Marie Pinvidic, Camille Lescot, Laura Trapiella-Alfonso, Institute of Chemistry for Life and Health Sciences (iCLeHS), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
biomedical applications, Biocompatibility, flow chemistry, Drug Compounding, [SDV]Life Sciences [q-bio], nanotheranostics, Pharmaceutical Science, Biocompatible Materials, Nanotechnology, Peptide, Review, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Analytical Chemistry, chemistry.chemical_compound, QD241-441, peptide synthesis, Drug Discovery, Peptide synthesis, Animals, Humans, [CHIM]Chemical Sciences, Tissue Distribution, Amino Acid Sequence, Particle Size, Physical and Theoretical Chemistry, Solid-Phase Synthesis Techniques, chemistry.chemical_classification, Drug Carriers, Organic Chemistry, Flow chemistry, 021001 nanoscience & nanotechnology, Nanostructures, 0104 chemical sciences, Amino acid, Characterization (materials science), chemistry, Chemistry (miscellaneous), peptide self-assembly, Molecular Medicine, Surface modification, Nanomedicine, physicochemical and biological characterization, Peptides, 0210 nano-technology
Abstract

International audience; There is a challenging need for the development of new alternative nanostructures that can allow the coupling and/or encapsulation of therapeutic/diagnostic molecules while reducing their toxicity and improving their circulation and in-vivo targeting. Among the new materials using natural building blocks, peptides have attracted significant interest because of their simple structure, relative chemical and physical stability, diversity of sequences and forms, their easy functionalization with (bio)molecules and the possibility of synthesizing them in large quantities. A number of them have the ability to self-assemble into nanotubes, -spheres, -vesicles or -rods under mild conditions, which opens up new applications in biology and nanomedicine due to their intrinsic biocompatibility and biodegradability as well as their surface chemical reactivity via amino- and carboxyl groups. In order to obtain nanostructures suitable for biomedical applications, the structure, size, shape and surface chemistry of these nanoplatforms must be optimized. These properties depend directly on the nature and sequence of the amino acids that constitute them. It is therefore essential to control the order in which the amino acids are introduced during the synthesis of short peptide chains and to evaluate their in-vitro and in-vivo physico-chemical properties before testing them for biomedical applications. This review therefore focuses on the synthesis, functionalization and characterization of peptide sequences that can self-assemble to form nanostructures. The synthesis in batch or with new continuous flow and microflow techniques will be described and compared in terms of amino acids sequence, purification processes, functionalization or encapsulation of targeting ligands, imaging probes as well as therapeutic molecules. Their chemical and biological characterization will be presented to evaluate their purity, toxicity, biocompatibility and biodistribution, and some therapeutic properties in vitro and in vivo. Finally, their main applications in the biomedical field will be presented so as to highlight their importance and advantages over classical nanostructures.

Published
2021

4. Development of Theranostic Cationic Liposomes Designed for Image-Guided Delivery of Nucleic Acid

Author

Johanne Seguin, Bich-Thuy Doan, Tawba Korichi, Corinne Marie, Hai Doan Do, Nathalie Mignet, Aude Michel, Hélène Dhotel, Christine Ménager, and Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Sonication, Pharmaceutical Science, lcsh:RS1-441, 02 engineering and technology, Gene delivery, magnetic cationic liposome, 030226 pharmacology & pharmacy, Article, lcsh:Pharmacy and materia medica, 03 medical and health sciences, 0302 clinical medicine, nucleic acid delivery, [CHIM]Chemical Sciences, Cationic liposome, Liposome, Chemistry, Transfection, 021001 nanoscience & nanotechnology, equipment and supplies, magnetic targeting, Drug delivery, Magnetofection, Biophysics, Magnetic nanoparticles, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 0210 nano-technology, human activities, magnetofection, MRI
Abstract

Cationic liposomes have been considered as potential vectors for gene delivery thanks to their ability to transfect cells with high efficiency. Recently, the combination of diagnostic agent and therapeutic agents in the same particle to form a theranostic system has been reported. Magnetic liposomes are one of these examples. Due to the magnetic nanoparticles encapsulated in the liposomes, they can act as a drug delivery system and, at the same time, a magnetic resonance imaging contrast enhancement agent or hyperthermia. In this work, nucleic acid delivery systems based on magnetic cationic liposomes (MCLs) were developed. Two different techniques, reverse phase evaporation and cosolvent sonication, were employed for liposome preparation. Both strategies produced MCLs of less than 200 nm with highly positive charge. Enhancement of their transverse and longitudinal relaxivities r2and r1 was obtained with both kinds of magnetic liposomes compared to free magnetic nanoparticles. Moreover, these MCLs showed high capacity to form complexes and transfect CT-26 cells using the antibiotic-free pFAR4-luc plasmid. The transfection enhancement with magnetofection was also carried out in CT26 cells. These results suggested that our MCLs could be a promising candidate for image-guided gene therapy.

Published
2020
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5. Mucoadhesive thermosensitive hydrogel for the intra-tumoral delivery of immunomodulatory agents, in vivo evidence of adhesion by means of non-invasive imaging techniques

Author

Cyrille Richard, Claude Capron, Nathalie Mignet, Christelle Lesieur, Johanne Seguin, Chantal Al Sabbagh, Bich-Thuy Doan, Robert Malafosse, Vincent Boudy, Katia Lemdani, Unité de Pharmacologie Chimique et Génétique (UPCG - UMR_S 640/UMR 8151), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-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 Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-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 Galien Paris-Sud (IGPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS), Unité de pharmacologie chimique et génétique et d'imagerie (UPCGI - UMR 8151 / UMR_S 1022 ), 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), Laboratoire épidémiologie et oncogénèse des tumeurs digestives, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Agence Générale des Equipements et Produits de Santé [Paris] (AGEPS), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), 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), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, 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), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-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)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
medicine.medical_treatment, [SDV]Life Sciences [q-bio], Pharmaceutical Science, 02 engineering and technology, CD8-Positive T-Lymphocytes, 030226 pharmacology & pharmacy, Mice, Drug Delivery Systems, 0302 clinical medicine, Bone Marrow, Neoplasms, Cytotoxic T cell, ComputingMilieux_MISCELLANEOUS, Mice, Inbred BALB C, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Optical Imaging, Adhesiveness, Hydrogels, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 021001 nanoscience & nanotechnology, 3. Good health, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Rheology, 0210 nano-technology, Adjuvant, Agonist, medicine.drug_class, [SDV.CAN]Life Sciences [q-bio]/Cancer, Poloxamer, 03 medical and health sciences, Immune system, In vivo, Cell Line, Tumor, medicine, Animals, Immunologic Factors, [CHIM]Chemical Sciences, Mucins, Granulocyte-Macrophage Colony-Stimulating Factor, Dendritic Cells, Mycobacterium tuberculosis, Colony-stimulating factor, In vitro, [CHIM.POLY]Chemical Sciences/Polymers, NIH 3T3 Cells, Cancer research, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, CD8
Abstract

Intratumoral injection of biocompatible gels is increasingly used for the sustained delivery of drugs and vaccines to enhance the anti-cancer immune response. Granulocyte-macrophage colony stimulating factor (GM-CSF) has become an attractive adjuvant thanks to its ability to boost the antitumor immune response by inducing proliferation, maturation and migration of the dendritic-cells (DCs) and the differentiation of lymphocytes. Killed Mycobacteria, such as Heat-killed Mycobacterium tuberculosis (HKMT) have been used in several studies as TLR-2 agonist to increase maturation of DCs. In this study, we designed a mucoadhesive thermosensitive formulation for the local delivery of GM-CSF and HKMT in order to enhance DCs activation and improve the local antitumor immune response. This formulation was selected based on its elastic and mucoadhesive properties obtained thanks to rheological studies. More importantly, intratumoral residence time of the labelled gel and protein were evidenced by means of MRI and non invasive in vivo optical imaging. Then, the efficacy of the combination of immunomodulators loaded thermogel was demonstated in vitro and in vivo. The selected thermogel exhibits rheological properties which confer a good elasticity and increased residence time of the immunostimulatory agents in the tumor, thus increasing the recruitment of DCs and T cytotoxic CD8+ lymphocytes.

Published
2019

6. In vitro distinction between proinflammatory and antiinflammatory macrophages with gadolinium-liposomes and ultrasmall superparamagnetic iron oxide particles at 3.0T

Author

Nathalie Mignet, Bernard E. Van Beers, Benjamin Leporq, Joao Piraquive, Jing Hong Wan, Wassef Khaled, Bich-Thuy Doan, Philippe Garteiser, Simon A. Lambert, Sophie Lotersztajn, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), RMN et optique : De la mesure au biomarqueur, 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-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), IRM Physiologique et Moléculaire de l'Abdomen, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Service d'imagerie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-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), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Beaujon-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Beaujon, 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 de la Recherche Agronomique (INRA), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), 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)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Service d'imagerie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris, Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Beaujon, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and 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)

Subjects
[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Gadolinium, [SDV]Life Sciences [q-bio], Contrast Media, chemistry.chemical_element, Inflammation, Endocytosis, Ferric Compounds, 030218 nuclear medicine & medical imaging, Proinflammatory cytokine, Flow cytometry, law.invention, Mice, 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0302 clinical medicine, Phagocytosis, Confocal microscopy, law, medicine, Animals, [CHIM]Chemical Sciences, Radiology, Nuclear Medicine and imaging, Magnetite Nanoparticles, ComputingMilieux_MISCELLANEOUS, Liposome, Microscopy, Confocal, medicine.diagnostic_test, Macrophages, Dextrans, Quantitative susceptibility mapping, Magnetic Resonance Imaging, Molecular biology, Phenotype, RAW 264.7 Cells, [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, chemistry, Liposomes, [SDV.IB]Life Sciences [q-bio]/Bioengineering, medicine.symptom, [CHIM.OTHE]Chemical Sciences/Other, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing
Abstract

BACKGROUND Inflammation involves a heterogeneous macrophage population, for which there is no readily available MR assessment method. PURPOSE To assess the feasibility of distinguishing proinflammatory M1 and antiinflammatory M2 macrophages at MRI enhanced with gadolinium liposomes or ultrasmall superparamagnetic iron oxide particles. STUDY TYPE In vitro. SPECIMEN We employed cultured RAW macrophages. M0 macrophages were polarized with lipopolysaccharide (LPS) or interleukin-4 (IL-4), resulting in M1 or M2 macrophages. The macrophages were incubated with gadolinium (±rhodamine) liposomes or iron oxide particles and cell pellets were prepared for MRI. FIELD STRENGTH/SEQUENCE Transverse relaxation rates and quantitative susceptibility were obtained at 3.0T with multiecho turbo spin echo and spoiled gradient echo sequences. ASSESSMENT MRI results were compared with confocal microscopy, flow cytometry, and expression of endocytosis, M1 and M2 genes. STATISTICAL TESTS Mann-Whitney and Kruskal-Wallis tests were performed. RESULTS Higher transverse relaxation rates and susceptibility were observed in M1 than in M2 and M0 macrophages (P < 0.01 both with liposomes and USPIO) and significantly different susceptibility in M2 and M0 macrophages (P < 0.01 both with liposomes and USPIO). These MRI results were confirmed at confocal microscopy and flow cytometry. LPS macrophages displayed M1 gene expression, whereas IL-4 macrophages showed M2 polarization and lower endocytosis gene expression rates. DATA CONCLUSION These in vitro results show that it is feasible to distinguish between proinflammatory M1 and antiinflammatory M2 macrophages according to their level of contrast agent uptake at MRI. LEVEL OF EVIDENCE 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1166-1173.

Published
2019

7. Design and Synthesis of Gold-Gadolinium-Core-Shell Nanoparticles as contrast agent: a Smart Way to Future Nanomaterials for Nanomedicine Applications

Author

Memona Khan, Frederik Tielens, Jolanda Spadavecchia, Fatima Aouidat, Sarah Boumati, Bich-Thuy Doan, Chemistry, Centre National de la Recherche Scientifique (CNRS), Chimie, Structures et Propriétés de Biomatériaux et d'Agents Thérapeutiques (CSPBAT), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 13 (UP13)-Institut Galilée-Université Sorbonne Paris Cité (USPC), and Savarin, Philippe

Subjects
Polymers, Gadolinium, Pharmaceutical Science, Nanoparticle, Contrast Media, Metal Nanoparticles, 02 engineering and technology, 01 natural sciences, Nanomaterials, International Journal of Nanomedicine, Drug Discovery, [CHIM] Chemical Sciences, Tissue Distribution, ComputingMilieux_MISCELLANEOUS, Original Research, Mice, Inbred BALB C, Cell Death, General Medicine, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, theoretical study, Magnetic Resonance Imaging, Nanomedicine, Colloidal gold, relaxivity, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 0210 nano-technology, MRI, Biodistribution, Materials science, Biocompatibility, Cell Survival, Biophysics, chemistry.chemical_element, Bioengineering, Nanotechnology, Gd-gold complex, 010402 general chemistry, Biomaterials, Animals, [CHIM]Chemical Sciences, biodistribution, [CHIM.MATE] Chemical Sciences/Material chemistry, Organic Chemistry, 0104 chemical sciences, Drug Liberation, Kinetics, [CHIM.POLY]Chemical Sciences/Polymers, chemistry, Gold, Nanoconjugates
Abstract

Fatima Aouidat,1 Sarah Boumati,2 Memona Khan,1 Frederik Tielens,3 Bich-Thuy Doan,2 Jolanda Spadavecchia1 1CNRS, UMR 7244, CSPBAT, Laboratory of Chemistry, Structures and Properties of Biomaterials And Therapeutic Agents University Paris 13, Sorbonne Paris Cité, Bobigny, France; 2UTCBS – Chimie ParisTech – University Paris Descartes - CNRS UMR 8258 – INSERM U1022 Equipe “Synthesis, Electrochemistry, Imaging and Analytical Systems for Diagnostics” SEISAD, Paris, France; 3General Chemistry (ALGC), Vrije University of Brussel (Free University Brussels-VUB), Brussel, BelgiumCorrespondence: Jolanda Spadavecchia Email jolanda.spadavecchia@univ-paris13.frIntroduction: The development of biopolymers for the synthesis of Gd(III) nanoparticles, as therapeutics, could play a key role in nanomedicine. Biocompatible polymers are not only used for complex monovalent biomolecules, but also for the realization of multivalent active targeting materials as diagnostic and/or therapeutic hybrid nanoparticles. In this article, it was reported for the first time, a novel synthesis of Gd(III)–biopolymer–Au(III) complex, acting as a key ingredient of core-shell gold nanoparticles (Gd(@AuNPs).Material and methods: The physical and chemical evaluation was carried out by spectroscopic analytical techniques (Raman spectroscopy, UV-visible and TEM). The theoretical characterization by DFT (density functional theory) analysis was carried out under specific conditions to investigate the interaction between the Au and the Gd precursors, during the first nucleation step. Magnetic features with relaxivity measurements at 7T were also performed as well as cytotoxicity studies on hepatocyte cell lines for biocompatibility studies. The in vivo detailed dynamic biodistribution studies in mice to characterize the potential applications for biology as MRI contrast agents were then achieved.Results: Physical–chemical evaluation confirms the successful design and reaction supposed. Viabilities of TIB-75 (hepatocytes) cells were evaluated using Alamar blue cytotoxic tests with increasing concentrations of nanoparticles. In vivo biodistribution studies were then accomplished to assess the kinetic behavior of the nanoparticles in mice and characterize their stealthiness property after intravenous injection.Conclusion: We demonstrated that Gd@AuNPs have some advantages to display hepatocytes in the liver. Particularly, these nanoconjugates give a good cellular uptake of several quantities of Gd@NPs into cells, while preserving a T1 contrast inside cells that provide a robust in vivo detection using T1-weighted MR images. These results will strengthen the role of gadolinium as complex to gold in order to tune Gd(@AuNPs) as an innovative diagnostic agent in the field of nanomedicine.Keywords: Gd-gold complex, theoretical study, MRI, relaxivity, biodistribution

Published
2019

8. Advances on non-invasive physically triggered nucleic acid delivery from nanocarriers

Author

Yohann Corvis, Brice Martin Couillaud, Nathalie Mignet, Hai Doan Do, Bich-Thuy Doan, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL), CCSD, Accord Elsevier, and 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 Cité (UPCité)

Subjects
Light, Endosome, Magnetic, Exogenous trigger, Pharmaceutical Science, 02 engineering and technology, Gene delivery, 03 medical and health sciences, Nucleic Acids, Nucleic acid delivery, Ultrasound, Animals, Humans, 030304 developmental biology, [SDV.IB] Life Sciences [q-bio]/Bioengineering, 0303 health sciences, [CHIM.MATE] Chemical Sciences/Material chemistry, Chemistry, Non invasive, Gene Transfer Techniques, Transfection, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, Cold Temperature, Magnetic Fields, Ultrasonic Waves, Target site, Biophysics, Nucleic acid, Nanoparticles, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Delivery system, Nanocarriers, 0210 nano-technology, Cold-shock
Abstract

International audience; Nucleic acids (NAs) have been considered as promising therapeutic agents for various types of diseases. However, their clinical applications still face many limitations due to their charge, high molecular weight, instability in biological environment and low levels of transfection. To overcome these drawbacks, therapeutic NAs should be carried in a stable nanocarrier, which can be viral or non-viral vectors, and released at specific target site. Various controllable gene release strategies are currently being evaluated with interesting results. Endogenous stimuli-responsive systems, for example pH-, redox reaction-, enzymatic-triggered approaches have been widely studied based on the physiological differences between pathological and normal tissues. Meanwhile, exogenous triggered release strategies require the use of externally non-invasive physical triggering signals such as light, heat, magnetic field and ultrasound. Compared to internal triggered strategies, external triggered gene release is time and site specifically controllable through active management of outside stimuli. The signal induces changes in the stability of the delivery system or some specific reactions which lead to endosomal escape and/or gene release. In the present review, the mechanisms and examples of exogenous triggered gene release approaches are detailed. Challenges and perspectives of such gene delivery systems are also discussed.

Published
2019
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9. 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

10. Gadolinium and Platinum in Tandem:Real-time Multi-Modal Monitoring of Drug Delivery by MRI and Fluorescence Imaging

Author

Ga Lai Law, René M. Botnar, Chi-Fai Chan, Sara Lacerda, Cyrille Richard, Grégory Ramniceanu, Ka-Leung Wong, Bich-Thuy Doan, Bethany I. Harriss, Alkystis Phinikaridou, Nicholas J. Long, Ka-Lok Ho, Hongguang Li, Rongfeng Lan, Wai Sum Lo, Hong Kong Baptist University (HKBU), Imperial College London, King‘s College London, 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)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), The Hong Kong Polytechnic University [Hong Kong] (POLYU), The Royal Society, LEGOUPIL, Laëtitia, and 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)

Subjects
Fluorescence-lifetime imaging microscopy, MRI contrast agent, Gadolinium, [SDV]Life Sciences [q-bio], Biomedical Engineering, Medicine (miscellaneous), chemistry.chemical_element, cisplatin, multi-modal, 010402 general chemistry, 01 natural sciences, 03 medical and health sciences, Nuclear magnetic resonance, fluorescence imaging, medicine, Therapy efficacy, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), 030304 developmental biology, Cisplatin, 0303 health sciences, Chemistry, Prodrug, 3. Good health, 0104 chemical sciences, Clearance time, [SDV] Life Sciences [q-bio], Drug delivery, drug delivery, prodrug, Biotechnology, medicine.drug, Biomedical engineering, Research Paper, MRI
Abstract

International audience; A novel dual-imaging cisplatin-carrying molecular cargo capable of performing simultaneous optical and MR imaging is reported herein. This long-lasting MRI contrast agent (r1 relaxivity of 23.4 mM-1s-1 at 3T, 25 oC) is a photo-activated cisplatin prodrug (PtGdL) which enables real-time monitoring of anti-cancer efficacy. PtGdL is a model for monitoring the drug delivery and anti-cancer efficacy by MRI with a much longer retention time (24 hours) in several organs such as renal cortex and spleen than GdDOTA and its motif control GdL. Upon complete release of cisplatin, all PtGdL is converted to GdL enabling subsequent MRI analyses of therapy efficacy within its reasonably short clearance time of 4 hours. There is also responsive fluorescence enhancement for monitoring by photon-excitation.

Published
2017

11. Mechanostereoselective One-Pot Synthesis of Functionalized Head-to-Head Cyclodextrin [3]Rotaxanes and Their Application as Magnetic Resonance Imaging Contrast Agents

Author

Célia S. Bonnet, Éva Tóth, Matthieu Sollogoub, Mickaël Ménand, Guillaume Vives, Jérémy Scelle, Jean Wilfried Fredy, Grégory Ramniceanu, Bernold Hasenknopf, Bich-Thuy Doan, Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-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)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), 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)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Parisien de Chimie Moléculaire ( IPCM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -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 Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), 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 ), 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 d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and ANR-16-CE09-0018,RotaxImage,Imagerie et diagnostic avec des polyrotaxanes(2016)

Subjects
chemistry.chemical_classification, medicine.diagnostic_test, Cyclodextrin, 010405 organic chemistry, Stereochemistry, Chemistry, Head to head, MRI contrast agent, Gadolinium, Organic Chemistry, One-pot synthesis, chemistry.chemical_element, Magnetic resonance imaging, 010402 general chemistry, [ CHIM ] Chemical Sciences, 01 natural sciences, Biochemistry, Combinatorial chemistry, Cycloaddition, 0104 chemical sciences, In vivo, medicine, [CHIM]Chemical Sciences, Physical and Theoretical Chemistry
Abstract

International audience; A versatile, five-component, one-pot synthesis of cyclodextrin (CD) [3]rotaxanes using copper-catalyzed azide–alkyne cycloaddition has been developed. Head-to-head [3]rotaxanes of α-CD selectively functionalized by one or two gadolinium 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid monoamide complexes were obtained mechanostereoselectively. The magnetic resonance imaging efficiency, expressed by the longitudinal proton relaxivity of the rotaxanes, was significantly improved as compared to the functionalized CD. In vitro and in vivo preclinical studies showed a higher contrast and retention in the kidney than gadolinium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex, demonstrating the potential of these rotaxanes as MRI contrast agent.

Published
2017

12. Lipidic spherulites as magnetic resonance imaging contrast agents

Author

Bich-Thuy Doan, C.A. Cuenod, Michel Bessodes, Nathalie Mignet, Sylvie Crauste-Manciet, Lauriane Jugé, Daniel Scherman, Claudie Bourgaux, Denis Brossard, and Hélène Dhotel

Subjects
medicine.diagnostic_test, Chemistry, media_common.quotation_subject, Magnetic resonance imaging, General Chemistry, Catalysis, Light scattering, Magnetic field, Paramagnetism, Nuclear magnetic resonance, Spherulite, Microscopy, Materials Chemistry, medicine, Contrast (vision), Macromolecule, media_common
Abstract

Magnetic resonance imaging is an excellent technique to achieve anatomical details and highly resolved images. The search for efficient contrast agents to increase the signal to background ratio led us to evaluate paramagnetic spherulites as potential Magnetic Resonance Imaging (MRI) contrast agents. Spherulites are supramolecular assemblies, made of lipidic concentric multilayers, able to encapsulate with high efficiency soluble macromolecules. Despite their highly interesting structure, spherulites have never been proposed as imaging agents. We proposed here three approaches to render spherulites paramagnetic: encapsulating a soluble contrastophore, inserting a lipidic contrastophore derivative or grafting a soluble contrastophore at the surface of the spherulites. Following similar strategies, liposomes were prepared for comparison. The conservation of the spherulite structure, throughout these three strategies, was shown by cryoelectron microscopy and small angle light scattering. The effect of the paramagnetic spherulites was studied by magnetic resonance imaging at different magnetic fields. The results showed that insertion of a contrastophore lipidic derivative into spherulite bilayers and grafting a contrastophore at the surface of the spherulites were the two strategies which led to the highest MRI contrast improvement.

Published
2014

14. Delayed hepatic uptake of multi-phosphonic acid poly(ethylene glycol) coated iron oxide measured by real-time Magnetic Resonance Imaging

Author

Grégory Ramniceanu, Jean-François Berret, Bich-Thuy Doan, C. Vezignol, Nathalie Mignet, Cédric Loubat, Alain Graillot, 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)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Specific polymers, CNRS UMR 7057 - Laboratoire Matières et Systèmes Complexes (MSC) (MSC), Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), Laboratoire de Recherche en Informatique (LRI), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), 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 Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Recherche en Informatique ( LRI ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Matière et Systèmes Complexes ( MSC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier ( ICGM ICMMM ), and Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
T-2 CONTRAST, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, General Chemical Engineering, Iron oxide, Nanoparticle, FOS: Physical sciences, Protein Corona, CELLULAR UPTAKE, 02 engineering and technology, Polyethylene glycol, engineering.material, 010402 general chemistry, 01 natural sciences, [SPI.MAT]Engineering Sciences [physics]/Materials, chemistry.chemical_compound, Coating, POLYETHYLENE-GLYCOL, PEG ratio, BIOMEDICAL APPLICATIONS, NANOPARTICLES, Physics - Biological Physics, IN-VIVO, chemistry.chemical_classification, [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], Biomolecules (q-bio.BM), General Chemistry, Polymer, 021001 nanoscience & nanotechnology, 0104 chemical sciences, SURFACE-CHARGE, Quantitative Biology - Biomolecules, chemistry, Biological Physics (physics.bio-ph), FOS: Biological sciences, engineering, [ PHYS.COND.CM-SCM ] Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft], CONTRAST AGENTS, 0210 nano-technology, Ethylene glycol, [PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft], PROTEIN CORONA, Nuclear chemistry, MRI
Abstract

We report on the synthesis, characterization, stability and pharmacokinetics of novel iron based contrast agents for magnetic resonance imaging (MRI). Statistical copolymers combining multiple phosphonic acid groups and poly(ethylene glycol) (PEG) were synthesized and used as coating agents for 10 nm iron oxide nanocrystals. In vitro, protein corona and stability assays show that phosphonic acid PEG copolymers outperform all other coating types examined, including low molecular weight anionic ligands and polymers. In vivo, the particle pharmacokinetics is investigated by monitoring the MRI signal intensity from mouse liver, spleen and arteries as a function of the time, between one minute and seven days after injection. Iron oxide particles coated with multi-phosphonic acid PEG polymers are shown to have a blood circulation lifetime of 250 minutes, i.e. 10 to 50 times greater than that of recently published PEGylated probes and benchmarks. The clearance from the liver takes in average 2 to 3 days and is independent of the core size, coating and particle stability. By comparing identical core particles with different coatings, we are able to determine the optimum conditions for stealth MRI probes., Comment: 19 pages 8 figures, RSC Advances, 2016

Published
2016
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15. 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

16. Perfluorooctyl Bromide Polymeric Capsules as Dual Contrast Agents for Ultrasonography and Magnetic Resonance Imaging

Author

Olivier Lucidarme, Jean-Claude Beloeil, Michèle Ourévitch, Nicolas Tsapis, Mathieu Santin, Nicolas Taulier, Bich Thuy Doan, Elias Fattal, Erol Kurtisovski, Belfor Galaz, Romain Berti, Emilia Pisani, S. Lori Bridal, Wladimir Urbach, and Brigitte Gillet

Subjects
Materials science, medicine.diagnostic_test, business.industry, Ultrasound, Second-harmonic imaging microscopy, Capsule, Magnetic resonance imaging, Condensed Matter Physics, Nanocapsules, Electronic, Optical and Magnetic Materials, Biomaterials, chemistry.chemical_compound, chemistry, In vivo, Bromide, Electrochemistry, medicine, business, Bolus (radiation therapy), Biomedical engineering
Abstract

Polymeric capsules with a thick shell made of biodegradable and biocompatible polymer and a liquid core of perfluorooctyl bromide (PFOB) were evaluated for stability as well as for ultrasound and magnetic resonance imaging (MRI) contrast enhancement. The method of preparation allows the mean capsule diameter to be regulated between 70nm and 25 μm and the capsule thickness-to-radius ratio from 0.25 to 0.54. Capsule diameter remains stable at 37 °C in phosphate buffer for at least 4 and 6 h for nanocapsules and microcapsules, respectively. The in vitro ultrasound signal-to-noise ratio (SNR) was measured from 40 to 60 MHz for 6 μm and 150 nm capsules: the SNR increases with capsule concentration up to 20-25 mg mL -1 , and then reaches a plateau that depends on capsule diameter (13.5 ± 1.5 dB for 6 μm and 6 ± 2 dB for the 150 nm capsules). The ultrasound SNR is stable for up to 20 min for microcapsules and for several hours for nanocapsules. For nanocapsules, the thinner the shell, the larger the SNR and the more compressible the capsules. Nanocapsule suspensions imaged in vitro with a commercial ultrasound imaging system (normal and tissue harmonic imaging modes, 7-14 MHz probe) were detected down to concentrations of 12.5 mg mL -1 . Injections of nanocapsules (200 μg ml -1 ) in mice in vivo reveal that the initial bolus passage presents significant ultrasound enhancement of the blood pool during hepatic imaging (7-14 MHz probe, tissue harmonic imaging mode). 19 F-MRI images were obtained in vitro at 9.4T using spin-echo and gradient echo sequences and allow detecting nanocapsules in suspension (50 mg mL -1 ). In conclusion, these results show initial feasibility for development of these capsules toward a dual-modality contrast agent.

Published
2008

17. Noncovalent Functionalization of Carbon Nanotubes with Amphiphilic Gd3+ Chelates: Toward Powerful T1 and T2 MRI Contrast Agents

Author

Jean-Claude Beloeil, Michel Bessodes, Éva Tóth, Daniel Scherman, Bich-Thuy Doan, and Cyrille Richard

Subjects
Materials science, Gadolinium, Inorganic chemistry, Contrast Media, chemistry.chemical_element, Bioengineering, 02 engineering and technology, Carbon nanotube, 010402 general chemistry, 01 natural sciences, law.invention, chemistry.chemical_compound, Nuclear magnetic resonance, law, Amphiphile, General Materials Science, Chelation, Chelating Agents, Aqueous solution, Nanotubes, Carbon, Mechanical Engineering, Relaxation (NMR), General Chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Magnetic Resonance Imaging, 0104 chemical sciences, chemistry, Surface modification, Stearic acid, 0210 nano-technology
Abstract

An amphiphilic gadolinium (III) chelate (GdL) was synthesized from commercially available stearic acid. Aqueous solutions of the complex at different concentrations (from 1 mM to 1 microM) were prepared and adsorbed on multiwalled carbon nanotubes. The resulting suspensions were stable for several days and have been characterized with regard to magnetic resonance imaging (MRI) contrast agent applications. Longitudinal water proton relaxivities, r1, have been measured at 20, 300, and 500 MHz. The r1 values show a strong dependence on the GdL concentration, particularly at low field. The relaxivities decrease with increasing field as it is predicted by the Solomon-Bloembergen-Morgan theory. Transverse water proton relaxation times, T2, have also been measured and are practically independent of both the frequency and the GdL concentration. An in vivo feasibility MRI study has been performed at 300 MHz in mice. A negative contrast could be well observed after injection of a suspension of functionalized nanotubes into the muscle of the leg of the mouse.

Published
2007

18. Preparation and Evaluation of Multiple Nanoemulsions Containing Gadolinium (III) Chelate as a Potential Magnetic Resonance Imaging (MRI) Contrast Agent

Author

Daniel Scherman, Yohann Corvis, Sylvie Crauste-Manciet, Philippe Espeau, Nathalie Mignet, Denis Brossard, Estelle Sigward, Johanne Seguin, Kadri Kindsiko, Bich-Thuy Doan, 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), and 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)

Subjects
Gadolinium DTPA, Materials science, RELAXIVITY, Gadolinium, MRI contrast agent, Chemistry, Pharmaceutical, Ultrafiltration, Pharmaceutical Science, chemistry.chemical_element, Contrast Media, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, DIFFERENTIAL SCANNING CALORIMETRY, DOUBLE EMULSIONS, Differential scanning calorimetry, Nuclear magnetic resonance, medicine, Pharmacology (medical), Chelation, SURFACTANTS, FORMULATION, Chelating Agents, Pharmacology, RELEASE, DRUG-DELIVERY SYSTEMS, medicine.diagnostic_test, Organic Chemistry, Magnetic resonance imaging, IN-VITRO, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 021001 nanoscience & nanotechnology, Magnetic Resonance Imaging, 0104 chemical sciences, Thermogravimetry, [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, chemistry, Positive contrast, ENHANCED MRI, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Molecular Medicine, Nanoparticles, DTPA, Emulsions, 0210 nano-technology, Biotechnology, Biomedical engineering
Abstract

International audience; The objective was to develop, characterize and assess the potentiality of W-1/O/W-2 self-emulsifying multiple nanoemulsions to enhance signal/noise ratio for Magnetic Resonance Imaging (MRI). For this purpose, a new formulation, was designed for encapsulation efficiency and stability. Various methods were used to characterize encapsulation efficiency ,in particular calorimetric methods (Differential Scanning Calorimetry (DSC), thermogravimetry analysis) and ultrafiltration. MRI in vitro relaxivities were assessed on loaded DTPA-Gd multiple nanoemulsions. Characterization of the formulation, in particular of encapsulation efficiency was a challenge due to interactions found with ultrafiltration method. Thanks to the specifically developed DSC protocol, we were able to confirm the formation of multiple nanoemulsions, differentiate loaded from unloaded nanoemulsions and measure the encapsulation efficiency which was found to be quite high with a 68% of drug loaded. Relaxivity studies showed that the self-emulsifying W/O/W nanoemulsions were positive contrast agents, exhibiting higher relaxivities than those of the DTPA-Gd solution taken as a reference. New self-emulsifying multiple nanoemulsions that were able to load satisfactory amounts of contrasting agent were successfully developed as potential MRI contrasting agents. A specific DSC protocol was needed to be developed to characterize these complex systems as it would be useful to develop these self-formation formulations.

Published
2015

19. Gadolinium-Doped Persistent Nanophosphors as Versatile Tool for Multimodal In Vivo Imaging

Author

Thomas Maldiney, Michel Bessodes, Daniel Scherman, Bich-Thuy Doan, Cyrille Richard, Damien Alloyeau, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), 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 Cité (UPCité), Université Paris Descartes - Paris 5 (UPD5), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL), Laboratoire Matériaux et Phénomènes Quantiques (MPQ (UMR_7162)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), ORANGE, Colette, Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)

Subjects
[PHYS.PHYS.PHYS-OPTICS] Physics [physics]/Physics [physics]/Optics [physics.optics], Materials science, LUMINESCENCE NANOPARTICLES, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Gadolinium, chemistry.chemical_element, Nanoprobe, Nanoparticle, Nanotechnology, 02 engineering and technology, [SPI.MAT] Engineering Sciences [physics]/Materials, 010402 general chemistry, 01 natural sciences, [SPI.MAT]Engineering Sciences [physics]/Materials, Biomaterials, DELIVERY, Persistent luminescence, MAGNETIC-RESONANCE, Electrochemistry, medicine, OXIDE NANOPARTICLES, [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], medicine.diagnostic_test, UNIFORM, Magnetic resonance imaging, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 0104 chemical sciences, Electronic, Optical and Magnetic Materials, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, chemistry, Nanocrystal, CELLS, CONTRAST AGENTS, Nanocarriers, 0210 nano-technology, Preclinical imaging
Abstract

International audience; Recent breakthroughs in the rational development of multifunctional nanocarriers have highlightened the advantage of combining the complementary forces of several imaging modalities into one single nanotool fully dedicated to the biomedical field and diagnosis applications. A novel multimodal optical-magnetic resonance imaging nanoprobe is introduced. Designed on the basis of a spinel zinc gallate structure doped with trivalent chromium and gadolinium, this nanocrystal bears the ability to serve as both a highly sensitive persistent luminescence nanoprobe for optical imaging, and a negative contrast agent for highly resolved magnetic resonance imaging (MRI). Additional proof is given that surface coverage can be modified in order to obtain stealth nanoparticles highly suitable for real-time in vivo application in mice, showing delayed reticulo-endothelial uptake and longer circulation time after systemic injection.

Published
2015

20. Single-cell detection by gradient echo 9.4 T MRI: a parametric study

Author

Brigitte Gillet, Claire Wilhelm, P. Smirnov, Florence Gazeau, Jean-Claude Beloeil, Bich-Thuy Doan, Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), 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)-Institut de Chimie du CNRS (INC), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Orléans (UO), and Centre National de la Recherche Scientifique (CNRS)

Subjects
Time Factors, Proton, Cell Survival, Cells, Iron, Dephasing, Ferric Compounds, 030218 nuclear medicine & medical imaging, Magnetics, 03 medical and health sciences, chemistry.chemical_compound, Magnetization, 0302 clinical medicine, Nuclear magnetic resonance, In vivo, medicine, Humans, Radiology, Nuclear Medicine and imaging, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Chemistry, Magnetic resonance imaging, equipment and supplies, Magnetic Resonance Imaging, Magnetic field, Spin echo, human activities, Iron oxide nanoparticles, HeLa Cells
Abstract

International audience; Recent studies have shown that cell migration can be monitored in vivo by magnetic resonance imaging after intracellular contrast agent incorporation. This is due to the dephasing effect on proton magnetization of the local magnetic field created by a labelled cell. Anionic iron oxide nanoparticles (AMNP) are among the most efficient and non-toxic contrast agents to be spontaneously taken up by a wide variety of cells. Here we measured the iron load and magnetization of HeLa turnout cells labelled with AMNP, as a function of the external magnetic field. High-resolution gradient echo 9.4T MRI detected individual labelled cells, whereas spin echo sequences were poorly sensitive. We then conducted a systematic study in order to determine the gradient echo sequence parameters (echo time, cell magnetization and resolution) most suitable for in vivo identification of single cells.

Published
2006

21. Use of magnetic resonance spectroscopy for the investigation of the CO2 dissolved in champagne and sparkling wines: a nondestructive and unintrusive method

Author

Gérard Liger-Belair, Jean-Marc Nuzillard, Philippe Jeandet, Jean-Claude Beloeil, Gwennhael Autret, Bich-Thuy Doan, Anne Dubois de Montreynaud, and Maryline Parmentier

Subjects
Wine, business.product_category, Chemistry, Relaxation (NMR), Analytical chemistry, Imaging spectrometer, 02 engineering and technology, Nuclear magnetic resonance spectroscopy, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, Biochemistry, 0104 chemical sciences, Analytical Chemistry, Matrix (chemical analysis), CO2 content, Bottle, Environmental Chemistry, 0210 nano-technology, business, Spectroscopy
Abstract

It is demonstrated in this paper that an imaging spectrometer with the 13 C Magnetic Resonance Spectroscopy (MRS) technique is an original unintrusive and nondestructive method, perfectly adapted to determine the amount of CO2 dissolved in a closed bottle of Champagne or Sparkling wine as well as the self-diffusion of CO2 in this matrix. Two Champagnes and one Sparkling wine were analyzed on a 7 T imaging spectrometer. It was necessary to use an imaging spectrometer with a large available bore to insert the bottle, localize the measurement and carry out 1 H and 13 C spectroscopy with a good sensitivity. In the 13 C spectra, CO2 and alcohol signals are well separated. By use of the quantity of ethanol acting as an internal reference, it was possible to deduce the CO 2 concentration. We determined the relaxation parameter T1 of CO2. Thanks to diffusion spectroscopy, the diffusion rate of the CO 2 in the closed bottle was also calculated. The method can easily be extended to study the CO2 content in closed bottles of other sparkling drinks, like beers, sodas, and fizzy waters. © 2004 Elsevier B.V. All rights reserved.

Published
2005

22. Follow-up by one- and two-dimensional NMR of plasma from pigs with ischemia-induced acute liver failure treated with a bioartificial liver

Author

Stephan Mahler, Jacques D. de Certaines, David Tréhout, Bruno Clément, Bich-Thuy Doan, Jeanne Desbois, Yannick Mallédant, Jean-Claude Beloeil, Benjamin Frémond, Mireille Desille, and Jean-Pierre Campion

Subjects
medicine.medical_specialty, business.industry, Encephalopathy, Bioartificial liver device, medicine.disease, law.invention, Cerebral edema, Glutamine, chemistry.chemical_compound, Endocrinology, Fulminant hepatic failure, chemistry, law, Internal medicine, Blood plasma, medicine, Molecular Medicine, Choline, Radiology, Nuclear Medicine and imaging, business, Hepatic encephalopathy, Spectroscopy
Abstract

Hepatic encephalopathy may occur following acute hepatic failure (AHF), which results in the release of toxic compounds from the injured liver. These compounds, which induce cerebral edema, are not well characterized, yet. The aim of this study was to evaluate the potential interest of NMR spectroscopy in the follow-up of different plasma compounds in pigs with ischemia-induced fulminant hepatic failure treated or not with a bioartificial liver (BAL), which has been previously shown to improve the neurological status of the animals. Qualitative analysis of pig plasma was achieved by one-dimensional-(1)H CPMG, two-dimensional homonuclear (1)H-(1)H TOCSY CPMG and heteronuclear (1)H-(13)C HSQC sequences. Semi-quantitative analysis of selected plasma metabolites along the disease evolution was carried out on pigs with ischemia-induced AHF treated with the BAL containing alginate beads with or without hepatocytes. A quantitative longitudinal follow-up was performed on characteristic metabolites via a one-dimensional CPMG sequence, including choline, glutamine, N-acetyl-glucosamine (NAG), pyruvate and trimethylamine-N-oxide (TMAO). The concentrations of choline and TMAO increased from the beginning to the end in animals treated with the BAL containing alginate beads without hepatocytes. Treatment of pigs with BAL containing hepatocytes resulted in an improvement of survival, the plasma concentrations of choline and TMAO being decreased in three out of five animals. Thus, NMR spectroscopy is a useful approach for the identification of toxic compounds which are involved in hepatic encephalopathy associated with AHF. These compounds can be cleared by a BAL resulting in the improvement of survival and neurological parameters of the animals.

Published
2002

23. Analysis of polyaromatics in crude gas oil mixtures: a new strategy using 1H 2D n.m.r

Author

B. Gillet, B. Blondel, Bich-Thuy Doan, and J.-C. Beloeil

Subjects
Anthracene, Resolution (mass spectrometry), business.industry, General Chemical Engineering, Organic Chemistry, Analytical chemistry, Energy Engineering and Power Technology, Benzothiophene, Phenanthrene, chemistry.chemical_compound, Fuel Technology, Petroleum product, chemistry, Molecule, business, Two-dimensional nuclear magnetic resonance spectroscopy, Naphthalene
Abstract

A new method for analysing complex mixtures, 1H 2D n.m.r., was used to determine polyaromatics in crude gas oil mixtures. 2D NMR overcomes the lack of resolution due to crowded 1D spectra and provides structural information. In particular, TOCSY (total correlation spectroscopy) 2D n.m.r. is well suited to polyaromatics because these molecules give specific 2D fingerprints which can be easily recognized. These patterns were selected and analysed in two ways: (1) specific fingerprint recognition using a pure compound library; (2) using the mixing time τm of the TOCSY sequence. Variation of τm gives a change in cross-peak intensities. The intensity variation curves are characteristic of spin systems and hence of the structures of compounds. Alkylated substitutions were also studied. The compounds were quantified. This strategy was used to analyse crude gas oils and measure the contents of separated alkylated naphthalene isomers, biphenyls, anthracene, phenanthrene and benzothiophene.

Published
1995

25. In vivo 2D 1H NMR of mdx mouse muscle and myoblast cells during fusion: Evidence for a characteristic signal of long chain fatty acids

Author

G. Berenger, B. Barbere, Jean-Claude Beloeil, A. Sebille, Bich-Thuy Doan, S. Morin, Jeanine Koenig, C. Verre-Serrie, M. Peres, and Brigitte Gillet

Subjects
Aging, mdx mouse, Magnetic Resonance Spectroscopy, Hindlimb, Cell Fusion, Mice, Mice, Neurologic Mutants, In vivo, medicine, Animals, Myocyte, Myopathy, Cells, Cultured, Genetics (clinical), chemistry.chemical_classification, Chemistry, Muscles, Fatty Acids, Fatty acid, Muscular Dystrophy, Animal, Cell biology, Mice, Inbred C57BL, Neurology, Biochemistry, Pediatrics, Perinatology and Child Health, Proton NMR, Neurology (clinical), medicine.symptom, Long chain, Hydrogen
Abstract

We have previously demonstrated that 2D 1H NMR is suitable for studying cerebral metabolism. The same technique was used to study the hind leg muscle of normal (C57BL10) and dystrophic (mdx) mice. The results were compared to preliminary results for cultured muscle cells to determine the origin of fatty acid signals.

Published
1993

26. Detection of enzymatic activity by PARACEST MRI: a general approach to target a large variety of enzymes

Author

Bernard Badet, Thomas Chauvin, Fanny Noury, Éva Tóth, Bich-Thuy Doan, Jean-Claude Beloeil, Michèle Bernier, Hervé Meudal, Philippe Durand, 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)-Institut de Chimie du CNRS (INC), Institut de Chimie des Substances Naturelles (ICSN), and Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)

Subjects
Lanthanide, PARACEST, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 010402 general chemistry, Cleavage (embryo), 01 natural sciences, Catalysis, Nuclear magnetic resonance, Organometallic Compounds, Chelation, lanthanides, Ytterbium, Nuclear Magnetic Resonance, Biomolecular, chemistry.chemical_classification, 010405 organic chemistry, Chemistry, Chemical exchange, Substrate (chemistry), General Medicine, General Chemistry, beta-Galactosidase, 0104 chemical sciences, Enzymes, Enzyme Activation, imaging agents, Enzyme, Saturation transfer, proton exchange, Molecular Probes, Biophysics, Molecular imaging, saturation transfer
Abstract

International audience; We report a new family of molecular imaging probes that offer the possibility of specific PARACEST (paramagnetic chemical exchange saturation transfer) MRI detection of a large variety of enzymatic activities. The probes are based on a lanthanide complex coupled to an enzyme-specific substrate through a self-immolative spacer. Upon enzymatic cleavage of the substrate, the spacer is spontaneously eliminated, thereby resulting in a remarkable change in the PARACEST properties of the Ln3+ chelate. This new type of contrast agent opens up new perspectives in molecular magnetic resonance imaging.

Published
2008

27. Chronic exposure to glufosinate-ammonium induces spatial memory impairments, hippocampal MRI modifications and glutamine synthetase activation in mice

Author

André-Guilhem Calas, William Même, Olivier Richard, Sandra Même, Wim E. Crusio, Bich-Thuy Doan, Jacques Pichon, Thierry Gefflaut, Céline Montécot, Jean-Claude Beloeil, Laboratoire de Neurobiologie, Université d'Orléans (UO), 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)-Institut de Chimie du CNRS (INC), Synthèse et étude de systèmes à intêret biologique (SEESIB), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Neurosciences cognitives (NC), Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), Université d'Orléans (UO)-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 Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Time Factors, Hippocampus, Spatial learning, Hippocampal formation, Toxicology, Mice, chemistry.chemical_compound, 0302 clinical medicine, Glutamate homeostasis, Neurotransmitter, 0303 health sciences, Behavior, Animal, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Aminobutyrates, General Neuroscience, Glutamate receptor, Magnetic Resonance Imaging, 3. Good health, medicine.anatomical_structure, Biochemistry, MRI, medicine.medical_specialty, Central nervous system, Biology, Glufosinate-ammonium, Glutamine synthetase, Chronic pesticide intoxication, 03 medical and health sciences, Glutamate-Ammonia Ligase, Internal medicine, medicine, Animals, Memory disorder, Maze Learning, 030304 developmental biology, Analysis of Variance, Memory Disorders, Chi-Square Distribution, Dose-Response Relationship, Drug, medicine.disease, Enzyme Activation, Mice, Inbred C57BL, Endocrinology, chemistry, Space Perception, Exploratory Behavior, 030217 neurology & neurosurgery
Abstract

International audience; Glufosinate-ammonium (GLA), the active compound of a worldwide-used herbicide, acts by inhibiting the plant glutamine synthetase (GS) leading to a lethal accumulation of ammonia. GS plays a pivotal role in the mammalian brain where it allows neurotransmitter glutamate recycling within astroglia. Clinical studies report that an acute GLA ingestion induces convulsions and memory impairment in humans. Toxicological studies performed at doses used for herbicidal activity showed that GLA is probably harmless at short or medium range periods. However, effects of low doses of GLA on chronically exposed subjects are not known. In our study, C57BL/6J mice were treated during 10 weeks three times a week with 2.5, 5 and 10 mg/kg of GLA. Effects of this chronic treatment were assessed at behavioral, structural and metabolic levels by using tests of spatial memory, locomotor activity and anxiety, hippocampal magnetic resonance imaging (MRI) texture analysis, and hippocampal GS activity assay, respectively. Chronic GLA treatments have effects neither on anxiety nor on locomotor activity of mice but at 5 and 10 mg/kg induce (1) mild memory impairments, (2) a modification of hippocampal texture and (3) a significant increase in hippocampal GS activity. It is suggested that these modifications may be causally linked one to another. Since glutamate is the main neurotransmitter in hippocampus where it plays a crucial role in spatial memory, hippocampal MRI texture and spatial memory alterations might be the consequences of hippocampal glutamate homeostasis modification revealed by increased GS activity in hippocampus. The present study provides the first data that show cerebral alterations after chronic exposure to GLA.

Published
2008

28. In vivo MRI assessment of a novel GdIII-based contrast agent designed for high magnetic field applications

Author

William Même, Jean-Claude Beloeil, Paulo Loureiro de Sousa, Carlos F. G. C. Geraldes, M. I. M. Prata, Lothar Helm, Ana C. Santos, Andre E. Merbach, Bich-Thuy Doan, João Bruno Livramento, Éva Tóth, 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)-Institut de Chimie du CNRS (INC), Laboratoire de Chimie Inorganique et Bioinorganique (LCIB), Ecole Polytechnique Fédérale de Lausanne (EPFL), Laboratoire de Neurobiologie, Université d'Orléans (UO), Laboratoire de Chimie Inorganique et Bioinorganique, laboratoire de Neurobiologie, Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centro de Fisica Computacional, University of Coimbra, Université de Coimbra, Instituto de Investigaçao das Pescas e do Mar, and Instituto Nacional de Pesquisas da Amazônia (INPA)

Subjects
Male, gamma imaging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Gadolinium, Inner sphere electron transfer, Kidney, 01 natural sciences, 030218 nuclear medicine & medical imaging, MESH: Magnetic Resonance Imaging, Mice, 0302 clinical medicine, Nuclear magnetic resonance, magnetic resonance imaging, Tissue Distribution, Whole Body Imaging, MESH: Animals, MESH: Organ Specificity, g imaging, high magnetic field, medicine.diagnostic_test, Chemistry, Relaxation (NMR), Brain, in vivo, Organ Specificity, MESH: Image Enhancement, pharmacokinetics, Biodistribution, Metabolic Clearance Rate, chemistry.chemical_element, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 010402 general chemistry, 03 medical and health sciences, MESH: Brain, Pharmacokinetics, MESH: Whole Body Imaging, In vivo, medicine, Animals, Radiology, Nuclear Medicine and imaging, contrast agents, MESH: Tissue Distribution, biodistribution, MESH: Mice, MESH: Metabolic Clearance Rate, Magnetic resonance imaging, MESH: Kidney, Image Enhancement, In vitro, MESH: Male, 0104 chemical sciences, gadolinium, MESH: Gadolinium
Abstract

International audience; Gd(3)L is a trinuclear Gd(3+) complex of intermediate size, designed for contrast agent applications in high field magnetic resonance imaging (H(12)L is based on a trimethylbenzene core bearing three methylene-diethylenetriamine- N,N,N'',N''-tetraacetate moieties). Thanks to its appropriate size, the presence of two inner sphere water molecules and a fast water exchange, Gd(3)L has remarkable proton relaxivities at high magnetic field (r(1) = 10.2 vs 3.0 mM(-1) s(-1) for GdDOTA at 9.4 T, 37 degrees C, in H(2)O). Here we report an in vivo MRI feasibility study, complemented with dynamic gamma scintigraphic imaging and biodistribution experiments using the (153)Sm-enriched analog. MRI experiments were performed at 9.4 T in mice with Gd(3)L and the commercial contrast agent gadolinium(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (GdDOTA). Gd(3)L was well tolerated by the animals at the dose of 8 micromol Gd kg(-1) body weight. Dynamic contrast enhanced (DCE) images showed considerably higher signal enhancement in the kidney medulla and cortex after Gd(3)L injection than after GdDOTA injection at an identical dose. The relaxation rates, DeltaR(1), were calculated from the IR TrueFISP data. During the excretory phase, the DeltaR(1) for various tissues was similar for Gd(3)L and GdDOTA, when the latter was injected at a three-fold higher dose (24 vs 8 micromol Gd kg(-1) body weight). These results point to an approximately three times higher in vivo relaxivity (per Gd) for Gd(3)L relative to GdDOTA, thus the ratio of the relaxivities of the two compounds determined in vitro is retained under in vivo conditions. They also indicate that the two inner sphere water molecules per Gd in Gd(3)L are not substantially replaced by endogenous anions or other donor groups under physiological conditions. Gd(3)L has a pharmacokinetics typical of small, hydrophilic complexes, involving fast renal clearance and no retention in the blood pool. The dynamic gamma scintigraphic studies and the biodistribution experiments performed in Wistar rats with (153)Sm-enriched (*)Sm(3)L are also indicative of a fast elimination via the kidneys.

Published
2008

29. Study of a potential inhibitor of acetylcholinesterase using UV spectrophotometry, NMR spectroscopy and molecular modeling

Author

Nello Ronzani, Isabelle Correia, Nicole Platzer, Jean-Claude Beloeil, Bich-Thuy Doan, Service de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, 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)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut de Chimie des Substances Naturelles (ICSN), and Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)

Subjects
[PHYS]Physics [physics], Molecular model, 010405 organic chemistry, medicine.drug_class, Stereochemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Nuclear magnetic resonance spectroscopy, 010402 general chemistry, 01 natural sciences, Acetylcholinesterase, 0104 chemical sciences, Hydrophobic effect, chemistry.chemical_compound, chemistry, Acetylcholinesterase inhibitor, Docking (molecular), Acridine, medicine, Pyridinium, Physical and Theoretical Chemistry, ComputingMilieux_MISCELLANEOUS
Abstract

1-[6-(Acridine-9-carbonyloxy)hexyl]pyridinium chloride (1) was synthesized and studied as a potential inhibitor of acetylcholinesterase (AChE), which is frequently involved in Alzheimer's disease. UV spectrophotometry showed that 1 is a reversible and competitive inhibitor of AChE (Ki ≈ 2 × 10−7 M). NMR (TrNOESY) showed that 1, bonded to AChE, maintains an extended form that allows hydrophobic interactions to occur between the aliphatic chain and the deep and narrow gorge of AchE and favors interactions between the acridine group and the catalytic and anionic subsites situated at the bottom of the gorge, and also between the pyridinium ring and the peripheral site. A more detailed picture of the structure of the complex was obtained by combining NMR structural data and molecular modeling (docking, dynamics simulation and energy calculations). Copyright © 2006 John Wiley & Sons, Ltd.

Published
2006

30. Study of inclusion complexes of acridine with β- and (2,6-di- O -methyl)-β-cyclodextrin by use of solubility diagrams and NMR spectroscopy

Author

Isabelle Correia, Nicole Platzer, Nello Ronzani, Bich-Thuy Doan, Nabil Bezzenine, Jean-Claude Beloeil, Université Pierre et Marie Curie - Paris 6 (UPMC), 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)-Institut de Chimie du CNRS (INC), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
chemistry.chemical_classification, Molecular model, Cyclodextrin, Stereochemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Substituent, 02 engineering and technology, Nuclear magnetic resonance spectroscopy, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, 0104 chemical sciences, chemistry.chemical_compound, chemistry, Docking (molecular), Computational chemistry, Acridine, Proton NMR, [CHIM]Chemical Sciences, Physical and Theoretical Chemistry, Solubility, 0210 nano-technology, ComputingMilieux_MISCELLANEOUS
Abstract

Previous molecular modeling studies, in our laboratory, have shown that some esters of type RCOO(CH2)nC5H5N+Cl− are potentially active against Alzheimer's disease. We have also demonstrated that acridine, which has strong anticholinesterase activity appears to be a suitable R substituent. The main obstacle to the possible pharmaceutical application of these compounds is their limited solubility in water, which is due to the poor aqueous solubility of acridine itself (0.26 mM). Inclusion complexation with cyclodextrins may overcome this problem. Solubility diagrams and NMR spectroscopy were used to study the inclusion of acridine (Acr) within β-cyclodextrin (βCD) and heptakis(2,6-di-O-methyl)cyclomaltoheptose (DMβCD). A 1:1 complex was formed for the Acr–βCD system and both 1:1 and 2:1 complexes for the Acr–DMβCD system (apparent Ka 215 ± 20 and 1150 ± 100 M−1, respectively). Data from 1H NMR studies corrected the assignment of the acridine H1, H8 and H4, H5 protons in D2O, which have been erroneously assigned in previous publications. 1H spin–lattice relaxation times T1 measured with selective, non-selective and null inversion characterize the dynamics of the inclusion complexes. Geometric features of the host–guest inclusion complexes were inferred from intermolecular dipolar interactions obtained by 2D adiabatic off-resonance ROESY experiments. A more detailed picture of the structure of the inclusion complexes was obtained by combining NMR structural data and molecular modeling (docking, dynamics under NMR constraints and energy calculations). Copyright © 2002 John Wiley & Sons, Ltd.

Published
2002

31. Chemical modifications of the vasoconstrictor peptide angiotensin II by nitrogen oxides (NO, HNO2, HOONO)--evaluation by mass spectrometry

Author

Laurent Serani, Claire Ducrocq, Didier Payen, Maryvonne Dendane, Bich-Thuy Doan, Abdelhak Karim, Brigitte Gillet, Alain Carayon, Bhupesh C. Das, Nadia Bouchemal-Chibani, and Olivier Laprévote

Subjects
Magnetic Resonance Spectroscopy, Arginine, Stereochemistry, Biochemistry, Mass Spectrometry, Rats, Sprague-Dawley, Residue (chemistry), chemistry.chemical_compound, Nitration, Animals, Humans, Vasoconstrictor Agents, Tyrosine, Reactive nitrogen species, Nitrates, Molecular Structure, Chemistry, Superoxide, Angiotensin II, Oxidants, Rats, Molecular Weight, Vasoconstriction, Nitrogen Oxides, Peroxynitrite
Abstract

Nitric oxide (NO) and angiotensin II are natural regulators of blood pressure. Under aerobic conditions, NO is transformed into its higher oxides (N2O4, NO2, NO/NO2 or N2O3) and oxoperoxonitrate (currently named peroxynitrite) by coupling with superoxide. Previous studies have shown that these reactive nitrogen species should be involved in vivo in the transformation of cysteine and tyrosine into the corresponding nitrosothiol and 3-nitrotyrosine. In the present study, attention has been focused on the relative reactivities of HNO2, peroxynitrite, and NO in the presence of dioxygen, towards the arginine and tyrosine residues of the peptide angiotensin II. Nitration of the tyrosine residue is clearly the main reaction with peroxynitrite. By contrast, besides 20 % of nitration of the tyrosine residue, NO in the presence of dioxygen leads to nitrosation reactions with the arginine residue similar to those observed with HNO2 at pH 5, possibly through the intermediate N2O3 reactive species. Angiotensin II is converted for the most part to peptides having lost either a terminal amine function or the whole guanido group, leading respectively to citrulline-containing angiotensin II or to a diene derivative. Identification established mainly by tandem mass spectrometry of peptidic by-products allows us to propose a cascade of nitrosations of all the amine functions of the arginine residue. Further in vivo studies show that transformations of the arginine residue in angiotensin II do not alter its vasoconstrictive properties, whereas nitration of the tyrosine residue totally inhibits them.

Published
1998

32. 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

33. 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

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