Multimodal imaging Gd-nanoparticles functionalized with Pittsburgh compound B or a nanobody for amyloid plaques targeting.

Jonathan Pansieri (1) , Marie Plissonneau (2, 3) , Nathalie Stransky-Heilkron (4) , Mireille Dumoulin (5) , Laurence Heinrich-Balard (6) , Pascaline Rivory (6) , Jean-François Morfin (7) , Éva Tóth (7) , Saraiva Maria Joao (8) , Eric Allémann (4) , Olivier Tillement (3) , Vincent Forge (1) , François Lux (3) , Christel Marquette (1)

1 LCBM - UMR 5249 - Laboratoire de Chimie et Biologie des Métaux
2 Nano-H S.A.S
3 ILM - Institut Lumière Matière [Villeurbanne]
4 School of Pharmaceutical Sciences
5 Laboratoire d'Enzymologie et Repliement des Protéines, Centre d'Ingénierie des Protéines
6 MATEIS - Matériaux, ingénierie et science [Villeurbanne]
7 CBM - Centre de biophysique moléculaire
8 Instituto de Inovação e Investigação em Saúde (I3S), University of Porto, Portugal

Gadolinium-based nanoparticles were functionalized with either the Pittsburgh compound B or a nanobody (B10AP) in order to create multimodal tools for an early diagnosis of amyloidoses.MATERIALS & METHODS:The ability of the functionalized nanoparticles to target amyloid fibrils made of β-amyloid peptide, amylin or Val30Met-mutated transthyretin formed in vitro or from pathological tissues was investigated by a range of spectroscopic and biophysics techniques including fluorescence microscopy.RESULTS:Nanoparticles functionalized by both probes efficiently interacted with the three types of amyloid fibrils, with KD values in 10 micromolar and 10 nanomolar range for, respectively, Pittsburgh compound B and B10AP nanoparticles. Moreover, they allowed the detection of amyloid deposits on pathological tissues.CONCLUSION:Such functionalized nanoparticles could represent promising flexible and multimodal imaging tools for the early diagnostic of amyloid diseases, in other words, Alzheimer's disease, Type 2 diabetes mellitus and the familial amyloidotic polyneuropathy.

Mots clés: nanobody; PIB; amyloidoses; gadolinium-based nanoparticles; amyloid imaging

Domaines: Biophysique; Imagerie; Médecine humaine et pathologie; Neurosciences [q-bio.NC]

Jonathan Pansieri, Marie Plissonneau, Nathalie Stransky-Heilkron, Mireille Dumoulin, Laurence Heinrich-Balard, et al.. Multimodal imaging Gd-nanoparticles functionalized with Pittsburgh compound B or a nanobody for amyloid plaques targeting.. Nanomedicine, 2017, 12 (14), pp.1675-1687. ⟨10.2217/nnm-2017-0079⟩. ⟨hal-01561318⟩