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23 results on '"Bich-Thuy Doan"'

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. 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

5. 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

6. 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

7. 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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8. 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

9. 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

10. 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

11. 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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12. 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

13. 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

14. 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

15. 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

16. 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

18. 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
Full Text
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19. 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

20. 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

21. 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

22. 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

23. 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

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