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Specific Macrophage Targeting for MRI Using Amyloid β Oligomer‐Labeled Nanoparticles
Author(s) -
Fuchs AnnKathrin,
Kumar Senthil,
Büchele Berthold,
Syrovets Tatiana,
Fändrich Marcus,
Simmet Thomas
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.577.5
Subject(s) - oligomer , chemistry , biophysics , macrophage , fibril , context (archaeology) , peptide , iron oxide nanoparticles , nanoparticle , nanotechnology , materials science , biochemistry , in vitro , biology , paleontology , organic chemistry
Amyloid β (Aβ) fibrils are strongly involved in the pathogenesis of Alzheimer's diseases. The Aβ oligomers represent a non‐fibrillar intermediate state of fibril formation.Here we explored the potential of Aβ peptide oligomers as a novel class of biological nanoparticles for macrophage targeting. This study shows that Aβ(1‐40) peptide oligomers have a near‐spheroid shape and due to a β‐sheet assembly possess a compact, quasi‐crystalline architecture. Additionally, FRET analysis revealed that Aβ(1‐40) are structurally dynamic. Hence, they represent highly structured and biocompatible nanoparticles, which can be readily degraded by natural enzymes. Macrophages play a major role in immunity and tissue repair. However, recent evidence implicates them in progression of atherosclerosis, fibrosis, tumor initiation and development. In this context, specific labeling and imaging of macrophages are of special interest for diagnostic and therapeutic applications. We found that oligomeric Aβ(1‐40) is preferentially taken up by macrophages compared to peripheral mononuclear cells. This prompted us to conjugate oligomeric Aβ(1‐40) to nanoparticles composed of a superparamagnetic iron oxide (SPIO) core and a polymeric shell used to increase contrast in magnetic resonance imaging (MRI). Such functionalization enabled the preferential uptake of SPIO‐Aβ contrast agents by macrophages. Thus, functionalization with Aβ oligomers might be used to diagnose disease‐associated macrophage accumulation by MRI.