Gd-nanoparticles functionalization with specific peptides for ß-amyloid plaques targeting
| Autor: | Éva Tόth, François Lux, Cédric Louis, Pierre Mowat, Eric Allémann, Laurence Heinrich-Balard, Mireille Dumoulin, Jonathan Pansieri, Richard Cohen, Nathalie Martine Stransky-Heilkron, Marie Plissonneau, C. Marquette, Olivier Tillement, Pascaline Rivory, Maria João Saraiva, Vincent Forge, Jean-François Morfin |
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| Přispěvatelé: | Nano-H SAS, 38070, Saint Quentin Fallavier, France., Nano-H SAS, 38070, Saint Quentin Fallavier, France, Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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)-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), Matériaux, ingénierie et science [Villeurbanne] (MATEIS), 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)-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)-Institut de Chimie du CNRS (INC), School of Pharmaceutical Sciences, University of Geneva [Switzerland], Centre for Protein Engineering (CIP), Institut de Chimie (B6) - Sart Tilman, Laboratoire d’Enzymologie et Repliement des Protéines, Université de Liège, Laboratoire de biochimie et biologie moléculaire, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Department of Molecular Neurobiology, Institute for Molecular and Cell Biology, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Genève = University of Geneva (UNIGE), Centre d’Ingénierie des Protéines [Université de Liège] = Centre for Protein Engineering [University of Liège] (CIP), Universidade do Porto = University of Porto |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Gene Expression Metal Nanoparticles Pharmaceutical Science Medicine (miscellaneous) Gadolinium Plaque Amyloid Peptide Beta-amyloid Hippocampus Applied Microbiology and Biotechnology Mice chemistry.chemical_compound 0302 clinical medicine Peptide-targeting Prealbumin MRI contrast agent Beta-amyloid fibrils chemistry.chemical_classification ddc:615 biology medicine.diagnostic_test Alzheimer's disease Magnetic Resonance Imaging Contrast agent Positron emission tomography Molecular Medicine Female Alzheimer’s disease FibrilsMRI Protein Binding medicine.medical_specialty Gadolinium based nanoparticles Amyloid Biomedical Engineering Mice Transgenic Bioengineering macromolecular substances Fibril Amyloid imaging 03 medical and health sciences Alzheimer Disease medicine Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Peptidetargeting Amyloid beta-Peptides Research Surface Plasmon Resonance medicine.disease Peptide Fragments Disease Models Animal Kinetics Transthyretin 030104 developmental biology chemistry Mutation Biophysics biology.protein Peptides Pittsburgh compound B [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology 030217 neurology & neurosurgery |
| Zdroj: | Journal of Nanobiotechnology Journal of Nanobiotechnology, BioMed Central, 2016, 14 (1), pp.60. ⟨10.1186/s12951-016-0212-y⟩ Journal of Nanobiotechnology, 2016, 14 (1), pp.60. ⟨10.1186/s12951-016-0212-y⟩ Journal of Nanobiotechnology, Vol. 14, No 1 (2016) |
| ISSN: | 1477-3155 |
| DOI: | 10.1186/s12951-016-0212-y |
| Popis: | Background Amyloidoses are characterized by the extracellular deposition of insoluble fibrillar proteinaceous aggregates highly organized into cross-β structure and referred to as amyloid fibrils. Nowadays, the diagnosis of these diseases remains tedious and involves multiple examinations while an early and accurate protein typing is crucial for the patients’ treatment. Routinely used neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) using Pittsburgh compound B, [11C]PIB, provide structural information and allow to assess the amyloid burden, respectively, but cannot discriminate between different amyloid deposits. Therefore, the availability of efficient multimodal imaging nanoparticles targeting specific amyloid fibrils would provide a minimally-invasive imaging tool useful for amyloidoses typing and early diagnosis. In the present study, we have functionalized gadolinium-based MRI nanoparticles (AGuIX) with peptides highly specific for Aβ amyloid fibrils, LPFFD and KLVFF. The capacity of such nanoparticles grafted with peptide to discriminate among different amyloid proteins, was tested with Aβ(1–42) fibrils and with mutated-(V30M) transthyretin (TTR) fibrils. Results The results of surface plasmon resonance studies showed that both functionalized nanoparticles interact with Aβ(1–42) fibrils with equilibrium dissociation constant (Kd) values of 403 and 350 µM respectively, whilst they did not interact with V30M-TTR fibrils. Similar experiments, performed with PIB, displayed an interaction both with Aβ(1–42) fibrils and V30M-TTR fibrils, with Kd values of 6 and 10 µM respectively, confirming this agent as a general amyloid fibril marker. Thereafter, the ability of functionalized nanoparticle to target and bind selectively Aβ aggregates was further investigated by immunohistochemistry on AD like-neuropathology brain tissue. Pictures clearly indicated that KLVFF-grafted or LPFFD-grafted to AGuIX nanoparticle recognized and bound the Aβ amyloid plaque localized in the mouse hippocampus. Conclusion These results constitute a first step for considering these functionalized nanoparticles as a valuable multimodal imaging tool to selectively discriminate and diagnose amyloidoses. Electronic supplementary material The online version of this article (doi:10.1186/s12951-016-0212-y) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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