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

Nanomedicine (Lond). 2017 Jul;12(14):1675-1687. doi: 10.2217/nnm-2017-0079. Epub 2017 Jun 21.

Abstract

Aim: 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.

Keywords: PIB; amyloid imaging; amyloidoses; gadolinium-based nanoparticles; nanobody.

MeSH terms

  • Alzheimer Disease / diagnosis
  • Amyloid beta-Peptides / analysis
  • Aniline Compounds / chemistry*
  • Animals
  • Brain / pathology
  • Diabetes Mellitus, Type 2 / diagnosis
  • Gadolinium / chemistry*
  • Humans
  • Immunohistochemistry
  • Islet Amyloid Polypeptide / analysis
  • Mice
  • Multimodal Imaging
  • Nanoparticles / chemistry*
  • Plaque, Amyloid / diagnosis*
  • Single-Domain Antibodies / chemistry*
  • Thiazoles / chemistry*

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Islet Amyloid Polypeptide
  • Single-Domain Antibodies
  • Thiazoles
  • Gadolinium