Antibody-conjugated, dual-modal, near-infrared fluorescent iron oxide nanoparticles for antiamyloidgenic activity and specific detection of amyloid-beta fibrils

Amyloid-beta (A beta) peptide is the main fibrillar component of plaque deposits found in brains affected by Alzheimer's disease (AD) and is related to the pathogenesis of AD. -Passive anti-A beta immunotherapy has emerged as a promising approach for the therapy of AD, based on the administration of specific anti-A beta monoclonal antibodies (aA beta mAbs) to delay A beta aggregation in the brain. However, the main disadvantage of this approach is the required readministration of the aA beta mAbs at frequent intervals. There are only a few reports describing in vitro study for the immobilization of aA beta mAbs to nanoparticles as potential targeting agents of A beta aggregates. In this article, we report the immobilization of the aA beta mAb clone BAM10 to near-infrared fluorescent maghemite nanoparticles for the inhibition of A beta(40) fibrillation kinetics and the specific detection of A beta(40) fibrils. The BAM10-conjugated iron oxide nanoparticles were well-characterized, including their immunogold labeling and cytotoxic effect on PC-12 (pheochromocytoma cell line). Indeed, these antibody-conjugated nanoparticles significantly inhibit the A beta(40) fibrillation kinetics compared with the same concentration, or even five times higher, of the free BAM10. This inhibitory effect was confirmed by different assays such as the photo-induced crosslinking of unmodified proteins combined with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A cell viability assay also confirmed that these antibodyconjugated nanoparticles significantly reduced the A beta(40)-induced cytotoxicity to PC-12 cells. Furthermore, the selective labeling of the A beta(40) fibrils with the BAM10-conjugated near-infrared fluorescent iron oxide nanoparticles enabled specific detection of A beta(40) fibrils ex vivo by both magnetic resonance imaging and fluorescence imaging. This study highlights the immobilization of the aA beta mAb to dual-modal nanoparticles as a potential approach for aA beta mAb delivery, eliminating the issue of readministration, and contributes to the development of multifunctional agents for diagnosis and therapy of AD.