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.

Perspective of Surfactant‐Free Colloidal Nanoparticles in Heterogeneous Catalysis

“…The LAL technique grants both options of either obtaining pure or modified nanoparticle surfaces after subsequent functionalization. In the latter case, starting from the natural (surfactant‐free) surface, functionalization and sub‐monolayer surfactant coverages of various organic molecules are accessible . Hence, one of the major advantages of laser‐based catalyst preparation is the free accessibility of the nanoparticle surface providing model materials in various compositions without necessary procedural adaptions.…”

“…Hence, surfactant‐free nanoparticle systems provide an ideal reference system for mechanistic studies to develop or verify kinetics or structure‐activity correlations. A subsequently targeted functionalization either with surfactants or by deposition on support materials enables parametric studies where only a single parameter is varied while the others are maintained. Thus, surfactant‐free NPs may also be used as reference material for other independent investigations of nanoparticle properties in current research.…”

“…Additionally, the surfactant‐free nanoparticle surfaces provide an ideal prerequisite for a systematic study of the influence of surfactants in comparison with bare NPs . Apart from that, intended NP functionalization can be performed independently of other additives to modify the particle properties even at sub‐monolayer concentrations . Hence, regarding scientific studies as well as potential industrial applications, the laser‐based catalyst preparation method offers the possibility of precisely designed nanomaterials with potentially augmented catalytic activity and selectivity.…”

Colloidal Metal Nanoparticles Prepared by Laser Ablation and their Applications

“…d) SERS signal of the analyte. [131] The interactions of bare NPs, free ligands, and NP-ligand conjugates on fibrillary Ab aggregationw as investigated. [117] Copyright2 008, American Chemical Society.…”

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