TY - JOUR
AU - Streich, Carmen
AU - Akkari, Laura
AU - Decker, Christina
AU - Bormann, Jenny
AU - Rehbock, Christoph
AU - Müller-Schiffmann, Andreas
AU - Niemeyer, Felix Carlsson
AU - Nagel-Steger, Luitgard
AU - Willbold, Dieter
AU - Sacca, Barbara
AU - Korth, Carsten
AU - Schrader, Thomas
AU - Barcikowski, Stephan
TI - Characterizing the Effect of Multivalent Conjugates Composed of Aβ-Specific Ligands and Metal Nanoparticles on Neurotoxic Fibrillar Aggregation
JO - ACS nano
VL - 10
IS - 8
SN - 1936-0851
CY - Washington, DC
PB - Soc.
M1 - FZJ-2017-01157
SP - 7582-7597
PY - 2016
AB - 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.
LB - PUB:(DE-HGF)16
UR - <Go to ISI:>//WOS:000381959100041
C6 - pmid:27404114
DO - DOI:10.1021/acsnano.6b02627
UR - https://juser.fz-juelich.de/record/826950
ER -