%0 Journal Article
%A Streich, Carmen
%A Akkari, Laura
%A Decker, Christina
%A Bormann, Jenny
%A Rehbock, Christoph
%A Müller-Schiffmann, Andreas
%A Niemeyer, Felix Carlsson
%A Nagel-Steger, Luitgard
%A Willbold, Dieter
%A Sacca, Barbara
%A Korth, Carsten
%A Schrader, Thomas
%A Barcikowski, Stephan
%T Characterizing the Effect of Multivalent Conjugates Composed of Aβ-Specific Ligands and Metal Nanoparticles on Neurotoxic Fibrillar Aggregation
%J ACS nano
%V 10
%N 8
%@ 1936-0851
%C Washington, DC
%I Soc.
%M FZJ-2017-01157
%P 7582-7597
%D 2016
%X Therapeutically active small molecules represent promising nonimmunogenic alternatives to antibodies for specifically targeting disease-relevant receptors. However, a potential drawback compared to antibody–antigen interactions may be the lower affinity of small molecules toward receptors. Here, we overcome this low-affinity problem by coating the surface of nanoparticles (NPs) with multiple ligands. Specifically, we explored the use of gold and platinum nanoparticles to increase the binding affinity of Aβ-specific small molecules to inhibit Aβ peptide aggregation into fibrils in vitro. The interactions of bare NPs, free ligands, and NP-bound ligands with Aβ are comprehensively studied via physicochemical methods (spectroscopy, microscopy, immunologic tests) and cell assays. Reduction of thioflavin T fluorescence, as an indicator for β-sheet content, and inhibition of cellular Aβ excretion are even more effective with NP-bound ligands than with the free ligands. The results from this study may have implications in the development of therapeutics for treating Alzheimer’s disease.
%F PUB:(DE-HGF)16
%9 Journal Article
%U <Go to ISI:>//WOS:000381959100041
%$ pmid:27404114
%R 10.1021/acsnano.6b02627
%U https://juser.fz-juelich.de/record/826950