Author: "Bich-Thuy Doan" - Searchworks@Jio Institute Digital Library Search Results

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1. Combination of thermal ablation by focused ultrasound, pFAR4-IL-12 transfection and lipidic adjuvant provide a distal immune response

Author: Hai Doan Do, Corinne Marie, Stéphanie Bessoles, Hélène Dhotel, Johanne Seguin, Benoit Larrat, Bich-Thuy Doan, Daniel Scherman, Virginie Escriou, Salima Hacein-Bey-Abina, and Nathalie Mignet
Subjects: gene delivery, cancer, transfection, immunotherapy, toll-like receptor 2-agonists, combined therapy, therapeutic ultrasound, Internal medicine, RC31-1245
Abstract: Aim: Gene-based immunotherapy against cancer is limited by low gene transfer efficiency. In the literature, interleukin-12 (IL-12) encoding plasmid associated with sonoporation has been shown to enhance antitumoral activity. Moreover, non-viral carriers and high-frequency ultrasound have both been shown to promote immune response activation. Here, IL-12 encoding plasmid, non-viral carrier stimulating the immune response and focused ultrasound were combined in order to improve the antitumoral efficiency. Methods: In order to enhance a gene-based antitumoral immune response, home-made lipids Toll-like receptor 2 (TLR2) agonists and plasmid free of antibiotic resistance version 4 (pFAR4), a mini-plasmid, encoding the IL-12 cytokine were combined with high-intensity focused ultrasound (HIFU). The lipid composition and the combination conditions were selected following in vitro and in vivo preliminary studies. The expression of IL-12 from our plasmid construct was measured in vitro and in vivo. The combination strategy was evaluated in mice bearing colon carcinoma cells (CT26) tumors following their weight, tumor volume, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) levels in the serum and produced by splenocytes exposed to CT26 tumor cells. Results: Lipid-mediated cell transfection and intratumoral injection into CT26 tumor mice using pFAR4-IL-12 led to the secretion of the IL-12 cytokine into cell supernatant and mice sera, respectively. Conditions of thermal deposition using HIFU were optimized. The plasmid encoding pFAR4-IL-12 or TLR2 agonist alone had no impact on tumor growth compared with control mice, whereas the complete treatment consisting of pFAR4-IL-12, TLR2 lipid agonist, and HIFU limited tumor growth. Moreover, only the complete treatment increased significantly mice survival and provided an abscopal effect on a metastatic CT26 model. Conclusions: The HIFU condition was highly efficient to stop tumor growth. The combined therapy was the most efficient in terms of IL-12 and IFN-γ production and mice survival. The study showed the feasibility and the limits of this combined therapy which has the potential to be improved.
Published: 2022
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2. Synthesis, Characterization and Evaluation of Peptide Nanostructures for Biomedical Applications

Author: Fanny d’Orlyé, Laura Trapiella-Alfonso, Camille Lescot, Marie Pinvidic, Bich-Thuy Doan, and Anne Varenne
Subjects: peptide synthesis, flow chemistry, peptide self-assembly, physicochemical and biological characterization, biomedical applications, nanotheranostics, Organic chemistry, QD241-441
Abstract: 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
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3. Development of Theranostic Cationic Liposomes Designed for Image-Guided Delivery of Nucleic Acid

Author: Hai Doan Do, Christine Ménager, Aude Michel, Johanne Seguin, Tawba Korichi, Hélène Dhotel, Corinne Marie, Bich-Thuy Doan, and Nathalie Mignet
Subjects: magnetic cationic liposome, nucleic acid delivery, magnetofection, MRI, magnetic targeting, Pharmacy and materia medica, RS1-441
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 r2 and 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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4. Both functional LTbeta receptor and TNF receptor 2 are required for the development of experimental cerebral malaria.

Author: Dieudonnée Togbe, Paulo Loureiro de Sousa, Mathilde Fauconnier, Victorine Boissay, Lizette Fick, Stefanie Scheu, Klaus Pfeffer, Robert Menard, Georges E Grau, Bich-Thuy Doan, Jean Claude Beloeil, Laurent Renia, Anna M Hansen, Helen J Ball, Nicholas H Hunt, Bernhard Ryffel, and Valerie F J Quesniaux
Subjects: Medicine, Science
Abstract: BackgroundTNF-related lymphotoxin alpha (LTalpha) is essential for the development of Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM). The pathway involved has been attributed to TNFR2. Here we show a second arm of LTalpha-signaling essential for ECM development through LTbeta-R, receptor of LTalpha1beta2 heterotrimer.Methodology/principal findingsLTbetaR deficient mice did not develop the neurological signs seen in PbA induced ECM but died at three weeks with high parasitaemia and severe anemia like LTalphabeta deficient mice. Resistance of LTalphabeta or LTbetaR deficient mice correlated with unaltered cerebral microcirculation and absence of ischemia, as documented by magnetic resonance imaging and angiography, associated with lack of microvascular obstruction, while wild-type mice developed distinct microvascular pathology. Recruitment and activation of perforin(+) CD8(+) T cells, and their ICAM-1 expression were clearly attenuated in the brain of resistant mice. An essential contribution of LIGHT, another LTbetaR ligand, could be excluded, as LIGHT deficient mice rapidly succumbed to ECM.Conclusions/significanceLTbetaR expressed on radioresistant resident stromal, probably endothelial cells, rather than hematopoietic cells, are essential for the development of ECM, as assessed by hematopoietic reconstitution experiment. Therefore, the data suggest that both functional LTbetaR and TNFR2 signaling are required and non-redundant for the development of microvascular pathology resulting in fatal ECM.
Published: 2008
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5. Chan-Vese based method to segment mouse brain MRI images: Application to cerebral malformation analysis in Trisomy 21.

Author: Ahmad Almhdie, Patricia Lopes-Pereira, Sandra Meme, Caroline Colombier, Veronique Brault, Frederic Szeremeta, Bich-Thuy Doan, Roger Lédée, Rachid Harba, Yann Herault, Jean-Claude Beloeil, and Christophe Léger
Published: 2009

6. 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

7. 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

8. Design and Synthesis of Gold-Gadolinium-Core-Shell Nanoparticles as Contrast Agent: a Smart Way to Future Nanomaterials for Nanomedicine Applications [Retraction]

Author: Fatima Aouidat, Sarah Boumati, Memona Khan, Frederik Tielens, Bich-Thuy Doan, and Jolanda Spadavecchia
Subjects: Biomaterials, International Journal of Nanomedicine, Organic Chemistry, Drug Discovery, Biophysics, Pharmaceutical Science, Bioengineering, General Medicine
Abstract: Aouidat F, Boumati S, Khan M, Tielens F, Doan BT, Spadavecchia J. Int J Nanomedicine. 2019;14:9309–9324. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. The authors raised concerns regarding errors that had been made during the calculation of the size of the nanostructures shown in Figure 2. The sizes reported in the histograms of Figure 2; a1, a2 and a3 were incorrect due to miscalculations that occurred during analysis of the gold core and polymer shells of the spherical nanostructures represented in TEM images of Figure 2A. The authors provided the editor with data from the original study and requested to remove the incorrect histograms and replace them. However, the Editor determined that this part of the article was integral to the study and the admission of these errors, because of the miscalculation, meant the data was unreliable and would not accept the correction proposed by the authors. The Editor requested for the article to be retracted and the authors were notified but do not agree with this decision. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.
Published: 2022

9. 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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10. 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

11. 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

12. 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

13. 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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14. 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

15. In Vivo Evaluation of Magnetic Targeting in Mice Colon Tumors with Ultra-Magnetic Liposomes Monitored by MRI

Author: Bich-Thuy Doan, Caroline J. Thébault, Claire Beauvineau, Johanne Seguin, Christian Girard, Grégory Ramniceanu, Nathalie Mignet, Christine Ménager, Aude Michel, 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), PHysicochimie des Electrolytes et Nanosystèmes InterfaciauX (PHENIX), Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), HAL-SU, Gestionnaire, 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 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)-ESPCI ParisTech-Université Pierre et Marie Curie - Paris 6 (UPMC), Chimie, Modélisation et Imagerie pour la Biologie [Orsay], Université Paris-Sud - Paris 11 (UP11)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'élaboration de matériaux et d'études structurales (CEMES), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-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), Liquides Ioniques et Interfaces Chargées (LI2C), 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 Pierre et Marie Curie - Paris 6 (UPMC)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cancer Research, Cell Survival, Magnetic nanoparticle, Image analysis method, [SDV.CAN]Life Sciences [q-bio]/Cancer, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Magnetics, Mice, Magnetic targeting, 0302 clinical medicine, In vivo, Cell Line, Tumor, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Medicine, Distribution (pharmacology), Animals, Radiology, Nuclear Medicine and imaging, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Magnetite Nanoparticles, ComputingMilieux_MISCELLANEOUS, Liposome, Mice, Inbred BALB C, Tumor, medicine.diagnostic_test, business.industry, Cancer, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Oncology, Liver, Drug delivery, Colonic Neoplasms, Liposomes, NIH 3T3 Cells, Female, Nanocarriers, business, Ex vivo, Biomedical engineering, MRI
Abstract: International audience; PurposeThe development of theranostic nanocarriers as an innovative therapy against cancer has been improved by targeting properties in order to optimize the drug delivery to safely achieve its desired therapeutic effect. The aim of this paper is to evaluate the magnetic targeting (MT) efficiency of ultra-magnetic liposomes (UML) into CT26 murine colon tumor by magnetic resonance imaging (MRI).ProceduresDynamic susceptibility contrast MRI was applied to assess the bloodstream circulation time. A novel semi-quantitative method called %I0.25, based on the intensity distribution in T2*-weighted MRI images was developed to compare the accumulation of T2 contrast agent in tumors with or without MT. To evaluate the efficiency of magnetic targeting, the percentage of pixels under the intensity value I0.25 (I0.25 = 0.25(Imax − Imin)) was calculated on the intensity distribution histogram.ResultsThis innovative method of processing MRI images showed the MT efficiency by a %I0.25 that was significantly higher in tumors using MT compared to passive accumulation, from 15.3 to 28.6 %. This methodology was validated by ex vivo methods with an iron concentration that is 3-fold higher in tumors using MT.ConclusionsWe have developed a method that allows a semi-quantitative evaluation of targeting efficiency in tumors, which could be applied to different T2 contrast agents.
Published: 2018

16. Clickable-Zwitterionic Copolymer Capped-Quantum Dots for in Vivo Fluorescence Tumor Imaging

Author: Anne Varenne, Christian Girard, Laura Trapiella-Alfonso, Edward Oujagir, Ludovic Leleu, Mariana Tasso, Nicolas Lequeux, Juliette Grimaldi, Thomas Pons, Bich-Thuy Doan, Johanne Seguin, Fanny d’Orlyé, Laboratoire de Physique et d'Etude des Matériaux (LPEM), Université Pierre et Marie Curie - Paris 6 (UPMC)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS), 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), Université Paris Descartes - Paris 5 (UPD5), ESPCI ParisTech-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Soft Matter Laboratory, Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas [La Plata] (INIFTA), Facultad de Ciencias Exactas [La Plata], Universidad Nacional de la Plata [Argentine] (UNLP)-Universidad Nacional de la Plata [Argentine] (UNLP)-Facultad de Ciencias Exactas [La Plata], Universidad Nacional de la Plata [Argentine] (UNLP)-Universidad Nacional de la Plata [Argentine] (UNLP), Georgia Tech - CNRS [Metz] (UMI2958), Ecole Nationale Supérieure des Arts et Metiers Metz-SUPELEC-Georgia Institute of Technology [Atlanta]-Georgia Institute of Technology [Lorraine, France]-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Laboratoire de Physique et d'Etude des Matériaux (UMR 8213) (LPEM), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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), Georgia Tech Lorraine [Metz], Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Ecole Supérieure d'Electricité - SUPELEC (FRANCE)-Georgia Institute of Technology [Atlanta]-CentraleSupélec-Ecole Nationale Supérieure des Arts et Metiers Metz-Centre National de la Recherche Scientifique (CNRS)
Subjects: Materials science, Biocompatibility, NEAR INFRARRED QUANTUM DOTS, Nanoprobe, Nanotechnology, 02 engineering and technology, INGENIERÍAS Y TECNOLOGÍAS, 010402 general chemistry, 01 natural sciences, CAPILLARY ELECTROPHORESIS, In vivo, OPTICAL IMAGING, Ingeniería de los Materiales, Neoplasms, Quantum Dots, Copolymer, Humans, General Materials Science, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, ComputingMilieux_MISCELLANEOUS, CANCER DIAGNOSIS, Optical Imaging, 021001 nanoscience & nanotechnology, Fluorescence, ZWITTERIONIC COPOLYMERS, 0104 chemical sciences, Characterization (materials science), Quantum dot, Click chemistry, CLICK CHEMISTRY, 0210 nano-technology, Peptides, RGD PEPTIDE
Abstract: In the last decades, fluorescent quantum dots (QDs) have appeared as high-performance biological fluorescent nanoprobes and have been explored for a variety of biomedical optical imaging applications. However, many central challenges still exist concerning the control of the surface chemistry to ensure high biocompatibility, low toxicity, antifouling, and specific active targeting properties. Regarding in vivo applications, circulation time and clearance of the nanoprobe are also key parameters to control the design and characterization of new optical imaging agents. Herein, the complete design and characterization of a peptide-near-infrared-QD-based nanoprobe for biomedical optical imaging is presented from the synthesis of the QDs and the zwitterionic-azide copolymer ligand, enabling a bio-orthogonal coupling, till the final in vivo test through all the characterization steps. The developed nanoprobes show high fluorescence emission, controlled grafting rate, low toxicity, in vitro active specific targeting, and in vivo long circulating blood time. This is, to our knowledge, the first report characterizing the in vivo circulation kinetics and tumor accumulation of targeted zwitterionic QDs. Fil: Trapiella Alfonso, Laura. Centre National de la Recherche Scientifique; Francia. Sorbonne Universite; Francia. Inserm; Francia. Université Paris Descartes; Francia. PSL Research University; Francia Fil: Pons, Thomas. Sorbonne Universite; Francia. Centre National de la Recherche Scientifique; Francia. PSL Research University; Francia Fil: Lequeux, Nicolas. Sorbonne Universite; Francia. PSL Research University; Francia. Centre National de la Recherche Scientifique; Francia Fil: Leleu, Ludovic. Université Paris Descartes; Francia. PSL Research University; Francia. Inserm; Francia. Centre National de la Recherche Scientifique; Francia Fil: Grimaldi, Juliette. Université Paris Descartes; Francia. PSL Research University; Francia. Centre National de la Recherche Scientifique; Francia. Inserm; Francia Fil: Tasso, Mariana Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Oujagir, Edward. Université Paris Descartes; Francia. Inserm; Francia. Centre National de la Recherche Scientifique; Francia Fil: Seguin, Johanne. Université Paris Descartes; Francia. Centre National de la Recherche Scientifique; Francia. Inserm; Francia Fil: d’Orlye, Fanny. Inserm; Francia. Centre National de la Recherche Scientifique; Francia. PSL Research University; Francia. Université Paris Descartes; Francia Fil: Girard, Christian. Inserm; Francia. PSL Research University; Francia. Centre National de la Recherche Scientifique; Francia. Université Paris Descartes; Francia Fil: Doan, Bich Thuy. PSL Research University; Francia. Inserm; Francia. Centre National de la Recherche Scientifique; Francia. Université Paris Descartes; Francia Fil: Varenne, Anne. PSL Research University; Francia. Inserm; Francia. Université Paris Descartes; Francia. Centre National de la Recherche Scientifique; Francia
Published: 2018

17. 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

18. 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

19. 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

20. INCREASED SENSITIVITY FOR MEDICAL IMAGING USING NON-IONIZING NANOMEDICINE AS CONTRAST AGENTS

Author: Nathalie Mignet, Bich-Thuy Doan, and Cyrille Richard
Subjects: Chemistry, media_common.quotation_subject, Medical imaging, Contrast (vision), Nanomedicine, Sensitivity (control systems), Non-ionizing radiation, Biomedical engineering, media_common
Published: 2016

21. 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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22. 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

23. MRI methodological development of intervertebral disc degeneration: a rabbit in vivo study at 9.4 T

Author: Frédéric Szeremeta, Fanny Noury, Jean-Claude Beloeil, Joël Mispelter, Bich-Thuy Doan, Sandra Même, Ingénierie de la vectorisation particulaire, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Interdisciplinaire de Recherche Ions Lasers (CIRIL), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur les Ions, les MAtériaux et la Photonique (CIMAP - UMR 6252), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Imagerie intégrative de la molécule à l'organisme, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Biophysique moléculaire, Institut Curie [Paris], 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), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-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 Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: musculoskeletal diseases, Materials science, Biomedical Engineering, Biophysics, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Degeneration (medical), 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Nuclear magnetic resonance, Lumbar, In vivo, Image Processing, Computer-Assisted, medicine, Animals, Effective diffusion coefficient, Radiology, Nuclear Medicine and imaging, medicine.diagnostic_test, Phantoms, Imaging, Rabbit (nuclear engineering), Intervertebral disc, Magnetic resonance imaging, musculoskeletal system, Magnetic Resonance Imaging, Disc height, Disease Models, Animal, medicine.anatomical_structure, Female, Rabbits, Intervertebral Disc Displacement, 030217 neurology & neurosurgery
Abstract: International audience; Intervertebral disc (IVD) degeneration is a complex process characterized by biochemical and structural changes in both the nucleus pulposus and the anulus fibrosus. In this study, we were able to obtain in vivo magnetic resonance (MR) images of the rabbit spine, with several MR imaging (MRI) contrasts (rho, T(1) and T(2)). We quantified several parameters (T(2), apparent diffusion coefficient, disc height and area) to differentiate between healthy and degenerative IVDs and to characterize the degeneration process. To our knowledge, there has not been any previous in vivo study of rabbit IVDs at high-field MRI (9.4 T). A custom radio frequency (RF) coil for 9.4 T was designed to match rabbit IVD morphology, to study the degeneration in vivo on a model of human lumbar disease. Our new probe, a custom half-birdcage-type coil, obtains the necessary exploration depth while meeting the requirements for signal homogeneity and sensitivity of the study. This design addresses some of the difficulties with constructing RF coils at high field strengths.
Published: 2008

24. 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

25. 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

26. Distinction between pro and anti-inflammatory macrophages using MRI relaxometry and quantitative susceptibility mapping

Author: Wassef Khaled, Benjamin Leporq, Wan, J. H., Philippe Garteiser, Lambert, Simon A., Nathalie Mignet, Bich-Thuy DOAN, Simona Manta, Sophie Lotersztajn, Bernard e. van Beers, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-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)), 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), Université Paris Descartes - Paris 5 (UPD5), Unité de pharmacologie chimique et génétique et d'imagerie (UPCGI - UMR 8151 / UMR_S 1022 ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), 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 Paris Descartes - Paris 5 (UPD5)-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), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)
Subjects: [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2015

27. Multimodal RM and Optic Imaging using ultramagnetic liposomes to monitor a cancer therapy

Author: Caroline Thébault, Grégory Ramniceanu, Johanne Seguin, Aude Michel, Claire Beauvineau, Christian Girard, Nathalie Mignet, Christine Ménager, 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), 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), PHysicochimie des Electrolytes et Nanosystèmes InterfaciauX (PHENIX), Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), LabEx MiChem, 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 sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Duchange, Nathalie, 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 ), PHysicochimie des Electrolytes et Nanosystèmes InterfaciauX ( PHENIX ), and Université Pierre et Marie Curie - Paris 6 ( UPMC ) -ESPCI ParisTech-Centre National de la Recherche Scientifique ( CNRS )
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, optical imaging, magnetic resonance imaging, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, nano medicine, equipment and supplies, human activities
Abstract: Congrès sous l’égide de la Société Française de Génie Biologique et Médical (SFGBM); National audience; Magnetic liposomes present an opportunity for the development of theranostic systems. Ultra-magnetic liposomes (UML) are highly loaded with ultra-small particles of iron oxide (USPIO) and can accumulate in a biological area thanks to a magnet. The incorporation of a fluorophore such as cyanine 5.5 in the formulation of the UML forms a bimodal imaging agent (MRI and optic) to monitor the magnetic accumulation in the tumor. The addition of an antitumoral drug into the UML combined with the application of High Intensity Focused Ultrasounds (HIFU) in the tumor can be used for a specific release of the drug in the region of interest.
Published: 2015

28. 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

29. 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

30. Phosphonate PEG Copolymers to control the USPIO stealthiness

Author: Gregory Ramniceanu, Bich-Thuy Doan, Camille Vezignol, Alain Graillot, Quentin Crouzet, Cedric Loubat, Nathalie Mignet, Jean-Francois Berret, Duchange, Nathalie, 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), Specific polymers, Unité de pharmacologie chimique et génétique et d'imagerie (UPCGI - UMR 8151 / UMR_S 1022 ), Université Paris Descartes - Paris 5 (UPD5)-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)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC), 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), Matière et Systèmes Complexes (MSC), Université Paris Diderot - Paris 7 (UPD7) - 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), and Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, Nanomedicine, Contrast agents USPIO, polymer coating, [SDV.IB]Life Sciences [q-bio]/Bioengineering, PEG, Magnetic Resonance Imaging
Abstract: Congrès sous l’égide de la Société Française de Génie Biologique et Médical (SFGBM); National audience; For nanomedicine applications, there is a need to design advanced and cost-effective coatings, resistant to protein adsorption leading to increased biodistribution in vivo. In this study, phosphonate poly(ethylene glycol) copolymers were synthesized and used to coat 6nm and 13nm iron oxide particle. In vitro, PEGylated particles exhibit exceptional stability and low cellular uptake, of the order of 100 femtograms of iron per cell. In vivo, we developed an in vivo Dynamic Susceptibility Weighted MRI (7T) protocol to monitor the hepatic capture and clearance of the particles injected to mice as a function of the time. PEGylated coat of molecular weight 2000 gmol-1 show a 2hrs delay to liver uptake as compared to the commercially available USPIO Cliavist, indicating a direct correlation between the surface properties of the contrast agents and their stealthiness.
Published: 2015

31. 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

32. Impaired voluntary running capacity of creatine kinase-deficient mice

Author: Patrick Lechêne, Renée Ventura-Clapier, Vladimir Veksler, Dominique Fortin, Jacqueline Hoerter, Xavier Bigard, Philippe Mateo, Bich Thuy Doan, Iman Momken, and Nathalie Koulmann
Subjects: Gene isoform, 0303 health sciences, medicine.medical_specialty, biology, Physiology, Stimulation, Anatomy, Peripheral blood mononuclear cell, Isozyme, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Myosin, biology.protein, medicine, Creatine kinase, Dobutamine, medicine.symptom, 030217 neurology & neurosurgery, 030304 developmental biology, Muscle contraction, medicine.drug
Abstract: The creatine kinase system (CK) is important for energy delivery in skeletal and cardiac muscles. The two main isoforms of this enzyme, cytosolic MM-CK and mitochondrial mi-CK, are expressed in a developmental and muscle-type specific manner. Mice deficient in one or both of these isoforms are viable and fertile but exhibit profound functional, metabolic and structural muscle remodelling that primarily affects fast skeletal muscles, which show an increased contribution of oxidative metabolism to contractile function. However, the consequences of these alterations in terms of physical capabilities have not yet been characterized. Consequently, we compared the voluntary exercise capacity of 9-month-old male wild-type (WT), M-CK knockout (M-CK(-/-)), and M-CK and mi-CK double knockout (CK(-/-)) mice, using cages equipped with running wheels. Exercise performance, calculated by total distance covered and by work done during the training period, was more than 10-fold lower in CK(-/-) mice than controls, with M-CK(-/-) mice exhibiting intermediate performance. Similarly, the mean distance run per activation was lower in M-CK(-/-) and even lower in CK(-/-) mice. However, the maximal running speed (V(max)) was lower only for CK(-/-) mice. This was accompanied by severe skeletal muscle mass decrease in CK(-/-) mice, with signs of histological damage that included enlarged interstitial areas, aggregations of mononuclear cells in the interstitium, heterogeneity of myofibre size and the presence of very small fibres. No overt sign of cardiac dysfunction was observed by magnetic resonance imaging during dobutamine stimulation. These results show that metabolic failure induced by CK deficiency profoundly affects the ability of mice to engage in chronic bouts of endurance running exercise and that this decrease in performance is also associated with muscle wasting.
Published: 2005

33. 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

34. In-vivo high resolution three-dimensional MRI studies of rat joints at 7 T

Author: P. Faure, Jean-Claude Beloeil, and Bich-Thuy Doan
Subjects: Pathology, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Cartilage, Rat model, High resolution, Arthritis, Magnetic resonance imaging, Mri studies, medicine.disease, medicine.anatomical_structure, In vivo, Rheumatoid arthritis, medicine, Molecular Medicine, Radiology, Nuclear Medicine and imaging, business, Nuclear medicine, Spectroscopy
Abstract: It is important to obtain high resolution images of joints for the study of disease, especially in rodent experimental models. We optimized 1H magnetic resonance imaging three-dimensional sequences at 7 T, with lipid signal suppression, and T1 and T2 measurements for in-vivo experiments on rat joints, in order to assess the effectiveness of high-field MRI. The method was validated by applying it to the early diagnosis of arthritis. We studied the progress of rheumatoid arthritis in an arthritic rat model. We observed the rats' knees for 21 days after inducing arthritis. The images acquired over one hour had a high resolution of 1.75 × 10−3 mm3, (105 × 105 × 145 μm3) which allowed us to spot the early stages of joint degeneration, such as bone erosion, and to observe an apparent ‘MRI’ loss of cartilage thickness, attributed to dehydration of the cartilage tissue. The MR images obtained during the early stages of rheumatoid arthritis enabled us to study joint changes accurately before any histological signs of attack were visible. Copyright © 2003 John Wiley & Sons, Ltd.
Published: 2003

35. 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

36. Prevention of rt-PA induced blood–brain barrier component degradation by the poly(ADP-ribose)polymerase inhibitor PJ34 after ischemic stroke in mice

Author: Frédéric Szeremeta, Niamh Slane, Marie Garraud, Isabelle Margaill, Bérard Coqueran, Catherine Marchand-Leroux, Michel Plotkine, Mélanie Kuntz, Clémentine Lesbats, Vincent Berezowski, Virginie Beray-Berthat, Daniel Scherman, Fei Teng, Cyrielle Bedfert, Bich-Thuy Doan, Bruno Palmier, Johan Hachani, Pharmacologie de la circulation cérébrale (EA 4475), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), 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), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA), 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 Descartes - Paris 5 (UPD5)-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)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL), and 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)
Subjects: Poly ADP ribose polymerase, [SDV]Life Sciences [q-bio], Ischemia, Pharmacology, Poly(ADP-ribose) Polymerase Inhibitors, Blood–brain barrier, Poly (ADP-Ribose) Polymerase Inhibitor, Brain Ischemia, Functional deficits, PARP, 03 medical and health sciences, Mice, 0302 clinical medicine, Developmental Neuroscience, N-dimethylamino)acetamide hydrochloride, PJ34, medicine, Animals, rt-PA, Stroke, 030304 developmental biology, Poly(ADP-ribose)polymerase (PARP), 6-dihydrophenanthridin-2-yl)-(N, 0303 health sciences, business.industry, Hemorrhagic transformation, Brain, N-(6-Oxo-5, Poly(ADP-ribose)polymerase, Phenanthrenes, Cerebral ischemia, medicine.disease, Molecular biology, In vitro, 3. Good health, Disease Models, Animal, medicine.anatomical_structure, Neurology, Blood-Brain Barrier, Tissue Plasminogen Activator, Recombinant tissue plasminogen activator (rt-PA), Toxicity, PARP inhibitor, recombinant tissue plasminogen activator, business, 030217 neurology & neurosurgery
Abstract: International audience; Recombinant tissue plasminogen activator (rt-PA) is the only pharmacological treatment approved for thrombolysis in patients suffering from ischemic stroke, but its administration aggravates the risk of hemorrhagic transformations. Experimental data demonstrated that rt-PA increases the activity of poly(ADP-ribose)polymerase (PARP). The aim of the present study was to investigate whether PJ34, a potent (PARP) inhibitor, protects the blood-brain barrier components from rt-PA toxicity. In our mouse model of cerebral ischemia, administration of rt-PA (10 mg/kg, i.v.) 6h after ischemia aggravated the post-ischemic degradation of ZO-1, claudin-5 and VE-cadherin, increased the hemorrhagic transformations (assessed by brain hemoglobin content and magnetic resonance imaging). Furthermore, rt-PA also aggravated ischemia-induced functional deficits. Combining PJ34 with rt-PA preserved the expression of ZO-1, claudin-5 and VE-cadherin, reduced the hemorrhagic transformations and improved the sensorimotor performances. In vitro studies also demonstrated that PJ34 crosses the blood-brain barrier and may thus exert its protective effect by acting on endothelial and/or parenchymal cells. Thus, co-treatment with a PARP inhibitor seems to be a promising strategy to reduce rt-PA-induced vascular toxicity after stroke.
Published: 2013

37. Evaluation of Nonradiative Clinical Imaging Techniques for the Longitudinal Assessment of Tumour Growth in Murine CT26 Colon Carcinoma

Author: Guy G. Chabot, Daniel Scherman, Heldmuth Latorre Ossa, Mickael Tanter, Lauriane Jugé, Johanne Seguin, Bich-Thuy Doan, Nathalie Mignet, and Jean-Luc Gennisson
Subjects: Pathology, medicine.medical_specialty, Noninvasive imaging, Article Subject, medicine.diagnostic_test, business.industry, Ultrasound, Magnetic resonance imaging, Histology, Text mining, Colon carcinoma, Cancer cell, Medicine, Radiology, Nuclear Medicine and imaging, Clinical imaging, Nuclear medicine, business, Research Article
Abstract: Background and Objectives. To determine the most appropriate technique for tumour followup in experimental therapeutics, we compared ultrasound (US) and magnetic resonance imaging (MRI) to characterize ectopic and orthotopic colon carcinoma models. Methods. CT26 tumours were implanted subcutaneously (s.c.) in Balb/c mice for the ectopic model or into the caecum for the orthotopic model. Tumours were evaluated by histology, spectrofluorescence, MRI, and US. Results. Histology of CT26 tumour showed homogeneously dispersed cancer cells and blood vessels. The visualization of the vascular network using labelled albumin showed that CT26 tumours were highly vascularized and disorganized. MRI allowed high-resolution and accurate 3D tumour measurements and provided additional anatomical and functional information. Noninvasive US imaging allowed good delineation of tumours despite an hypoechogenic signal. Monitoring of tumour growth with US could be accomplished as early as 5 days after implantation with a shorter acquisition time (Conclusion. MRI and US afforded excellent noninvasive imaging techniques to accurately follow tumour growth of ectopic and orthotopic CT26 tumours. These two techniques can be appropriately used for tumour treatment followup, with a preference for US imaging, due to its short acquisition time and simplicity of use.
Published: 2013

38. General Principles of MRI

Author: Sandra Même, Bich-Thuy Doan, and Jean-Claude Beloeil
Subjects: Materials science, Nuclear magnetic resonance, Interventional magnetic resonance imaging, Dynamic contrast-enhanced MRI, Magnetic resonance spectroscopic imaging
Published: 2013

39. 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

40. Identification of Polyaromatic Spin Systems of Complex Mixtures by TOCSY, Using Specific Time Dependence during Isotropic Mixing

Author: Bich-Thuy Doan, B. Blondel, J.-C. Beloeil, and B. Gillet
Subjects: Chemical physics, Chemistry, Specific time, Isotropy, General Engineering, Analytical chemistry, Pulse sequence, Analyse qualitative, Mixing (physics), Spin-½
Published: 1995

41. Colon tumor growth and antivascular treatment in mice: complementary assessment with MR elastography and diffusion-weighted MR imaging

Author: Bernard E. Van Beers, Lauriane Jugé, Daniel Scherman, Johanne Seguin, Nathalie Mignet, Ralph Sinkus, Valérie Vilgrain, Valérie Paradis, Bich-Thuy Doan, Miguel Albuquerque, Benoit Larrat, and Guy G. Chabot
Subjects: medicine.medical_specialty, Microcirculation, Neovascularization, Elasticity Imaging Techniques, Mice, Stilbenes, medicine, Animals, Radiology, Nuclear Medicine and imaging, Tumor growth, skin and connective tissue diseases, Diffusion-Weighted MR Imaging, Mice, Inbred BALB C, medicine.diagnostic_test, Neovascularization, Pathologic, business.industry, Mr imaging, Diffusion Magnetic Resonance Imaging, Tumor vascularity, Colonic Neoplasms, Female, sense organs, Radiology, Elastography, medicine.symptom, business
Abstract: To investigate the potential value of magnetic resonance (MR) elastography and diffusion-weighted (DW) MR imaging in the detection of microstructural changes of murine colon tumors during growth and antivascular treatment.The study was approved by the regional ethics committee for animal care. Sixty Balb-C mice, bearing ectopic and orthotopic colon tumors, were monitored for 3 weeks with high-resolution T2-weighted MR imaging, three-dimensional steady-state MR elastography, and DW MR imaging at 7 T. The same imaging protocol was performed 24 hours after injection of combretastatin A4 phosphate (CA4P) in 12 mice. The absolute value of the complex shear modulus (|G*|) and the apparent diffusion coefficient (ADC) were measured in the viable zones of tumors and compared with microvessel density (MVD), cellularity, and micronecrosis by using the Pearson correlation coefficient.During tumor growth, |G*| increase was correlated with MVD (r = 0.70 [P = .08] and r = 0.78 [P = .002], for both the ectopic and orthotopic models, respectively). Moreover, the ectopic tumors displayed decreased ADC, which correlated with increased cellularity (r = 0.77, P = .04), whereas no changes in ADC and cellularity were observed in orthotopic tumors. After CA4P administration, |G*| decreased in the ectopic model (P.0001), similar to the MVD evolution (P = .03), whereas no significant changes in |G*| (P = .7) and MVD (P = .6) were observed in the orthotopic model. ADC increased in both models (P = .047 and P = .01 for the ectopic and the orthotopic models, respectively) in relation to increased micronecrosis.Imaging of mechanical properties and diffusivity provide complementary information during tumor growth and regression that are respectively linked to vascularity and tumor cell alterations, including cellularity and micronecrosis.
Published: 2012

42. 2D NMR studies on muscle and cerebral metabolism in vivo

Author: C. Verre-Sebrie, J. C. Beloeil, O. Fedeli, B. Barrere, B. Gillet, J. Seylaz, M. Peres, J. Koenig, Bich-Thuy Doan, A. Sebille, and S. Morin
Subjects: Central nervous system, Cerebral metabolism, Anatomy, Hypoxia (medical), Biology, medicine.disease, Biochemistry, Molecular biology, Pathophysiology, Gastrocnemius muscle, medicine.anatomical_structure, In vivo, medicine, Muscular dystrophy, medicine.symptom
Abstract: Les recents developpements de la spectroscopie 1 H 2D in vivo ont rendu possible l'observation directe, in situ de metabolites generalement mal resolus par RMN ID. Nous presentons ici des applications de cette technique a des experiences de suivi metabolique lors de processus physiologiques et physiopathologiques, sur le cerveau de rat (hyperglycemie et hypoxie) et a l'etude comparative, sur le muscle, de la nature des chaines lipidiques entre souris normale et dystrophique
Published: 1994

43. 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

44. 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

45. Etude par IRM de l'impact de l'ingestion chronique d'un herbicide sur le système nerveux central chez la souris

Author: Sandra Même, André-Guilhem Calas, Céline Montécot, Olivier Richard, Thierry Gefflaut, Bich-Thuy DOAN, William Même, Jacques Pichon, Jean-Claude Beloeil, 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 Neurobiologie, Université d'Orléans (UO), 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), 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 Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: stomatognathic diseases, InformationSystems_MODELSANDPRINCIPLES, ComputingMilieux_THECOMPUTINGPROFESSION, GeneralLiterature_INTRODUCTORYANDSURVEY, ComputingMilieux_COMPUTERSANDEDUCATION
Abstract: Communication orale
Published: 2008

46. 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

47. 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

48. In vivo cellular imaging of lymphocyte trafficking by MRI : a tumor model approach to cell-based anticancer therapy

Author: Béhazine Combadière, Olivier Clément, Christophe Combadière, Alexandre Boissonnas, Elise Lavergne, Bich-Thuy Doan, Brigitte Gillet, Florence Gazeau, P. Smirnov, Maïté Lewin, Laboratoire de Recherche en Imagerie, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Matière et Systèmes Complexes (MSC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Immunologie cellulaire et tissulaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie des Substances Naturelles (ICSN), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pathology, medicine.medical_specialty, Lymphoma, Lymphocyte, Contrast Media, Spleen, Biology, Immunotherapy, Adoptive, Cell therapy, Mice, Immune system, In vivo, Cell Line, Tumor, Image Interpretation, Computer-Assisted, medicine, Splenocyte, Animals, Radiology, Nuclear Medicine and imaging, in vivo cellular imaging, Lymphocytes, [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], superparamagnetic iron oxide nanoparticles, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], Image Enhancement, lymphocyte trafficking, Magnetic Resonance Imaging, Mice, Inbred C57BL, medicine.anatomical_structure, Lymphocyte Transfusion, Feasibility Studies, Female, cell therapy, Ex vivo, Cell based, MRI
Abstract: The aim of this study was to demonstrate the feasibility of in vivo cell tracking to monitor anticancer cell therapy by means of a high-resolution noninvasive MRI method. Ovalbumin-specific splenocytes (OT-1) labeled with anionic -Fe2O3 superparamagnetic iron oxide (SPIO) nanoparticles were adoptively transferred into C57BL/6 mice with growing ovalbumin-expressing tumors. OT-1 cells were tracked in vivo by 7 T MRI 24, 48, and 72 hr after they were injected. The results showed significant negative enhancement of the spleen at 24 hr, and of the tumor at 48 and 72 hr, after labeled cell injection. This suggests that the lymphocytes initially homed toward the spleen and were then recruited by the tumor. The presence of labeled cells was confirmed in ex vivo by 9.4 T microimaging of tumors and magnetic sorting of spleen cells. These results confirm that MR tracking of lymphocytes is feasible in vivo. This high-resolution imaging method could be used to improve the monitoring of immune cell therapy. Magn Reson Med 56:498 –508, 2006.
Published: 2006

49. 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

50. Magnetic resonance imaging of Klebsiella pneumoniae-induced pneumonia in mice

Author: Philippe J. Sansonetti, Bich-Thuy Doan, Régis Tournebize, Marie-Agnès Dillies, Jean-Claude Beloeil, Sabine Maurin, Pathogénie Microbienne Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Puces à ADN (Plate-Forme 2) (PF2), Institut Pasteur [Paris], Histotechnologie et Pathologie, Institut Pasteur [Paris] (IP)-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 Pasteur [Paris] (IP)
Subjects: Klebsiella pneumoniae, Immunology, Virulence, Inflammation, Biology, Microbiology, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Mice, 0302 clinical medicine, In vivo, Virology, medicine, Pneumonia, Bacterial, Animals, Pathogen, Lung, 030304 developmental biology, 0303 health sciences, Mice, Inbred BALB C, medicine.diagnostic_test, Magnetic resonance imaging, biology.organism_classification, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Pneumonia, Female, medicine.symptom, Preclinical imaging
Abstract: Summary In vivo imaging of small animals is a rapidly developing field. However, the potential of global imaging of infectious processes in animal models remains poorly explored. We used magnetic resonance imaging (MRI) to follow the development and regression of inflammatory lesions caused by infection by Klebsiella pneumoniae in mouse lungs. A virulent strain caused an intense inflammation within 2 days in the whole lungs, while an avirulent strain did not show significant changes. Mice infected with the virulent strain and subsequently treated with antibiotics presented a severe inflammation localized mainly in the left lung that disappeared after a week. The lesions observed by MRI correlated with the damage seen by histological analysis and a 3D representation of the tissue allowed better visualization of the development and healing of inflammatory lesions. MRI thus represents a powerful technique to study in vivo the interactions between a pathogen and its host in real time.
Published: 2005

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