title: Characterizing the Effect of Multivalent Conjugates Composed of Aβ-Specific Ligands and Metal Nanoparticles on Neurotoxic Fibrillar Aggregation.
abstract: 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.
authors.affiliation: Technical Chemistry I and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen , 45141 Essen, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Streich
authors.affiliation: Institute for Organic Chemistry, University of Duisburg-Essen , 45117 Essen, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Akkari
authors.affiliation: Institut für Physikalische Biologie, Heinrich-Heine-University Düsseldorf , 40225 Düsseldorf, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Decker
authors.affiliation: Chemical Biology, Zentrum für Medizinische Biotechnologie (ZMB), Fakultät für Biologie, Universtität Duisburg-Essen , 45117 Essen, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Bormann
authors.affiliation: Technical Chemistry I and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen , 45141 Essen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Rehbock
authors.affiliation: Department Neuropathology, University of Düsseldorf Medical School , 40225 Düsseldorf, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Müller-Schiffmann
authors.affiliation: Institute for Organic Chemistry, University of Duisburg-Essen , 45117 Essen, Germany.
authors.forename: Felix Carlsson
authors.initials: FC
authors.lastname: Niemeyer
authors.affiliation: Institut für Physikalische Biologie, Heinrich-Heine-University Düsseldorf , 40225 Düsseldorf, Germany.|Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich , 52425 Jülich, Germany.
authors.forename: Luitgard
authors.initials: L
authors.lastname: Nagel-Steger
authors.affiliation: Institut für Physikalische Biologie, Heinrich-Heine-University Düsseldorf , 40225 Düsseldorf, Germany.|Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich , 52425 Jülich, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
authors.affiliation: Bionanotechnology, Zentrum für Medizinische Biotechnologie (ZMB), Fakultät für Biologie, University of Duisburg-Essen , 45117 Essen, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sacca
authors.affiliation: Department Neuropathology, University of Düsseldorf Medical School , 40225 Düsseldorf, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Korth
authors.affiliation: Institute for Organic Chemistry, University of Duisburg-Essen , 45117 Essen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schrader
authors.affiliation: Technical Chemistry I and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen , 45141 Essen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Barcikowski
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D006046:Gold; D008024:Ligands; D053768:Metal Nanoparticles; D010446:Peptide Fragments
chemical_list: D016229:Amyloid beta-Peptides; D008024:Ligands; D010446:Peptide Fragments; D006046:Gold
keywords: colloidal gold; cooperativity; misfolded proteins; multivalence; nanomedicine; neurodegenerative diseases; protein fibrillization