Characterizing the Effect of Multivalent Conjugates Composed of Aβ-Specific Ligands and Metal Nanoparticles on Neurotoxic Fibrillar Aggregation

作者：Carmen Streich, Laura Akkari, Christina Decker, Jenny Bormann, Christoph Rehbock, Andreas Müller‐Schiffmann, Felix C. Niemeyer, Luitgard Nagel‐Steger, Dieter Willbold, Barbara Saccà, Carsten Korth, Thomas Schräder, Stephan Barcikowski · 发表于：ACS Nano · 年份：2016 · DOI：10.1021/acsnano.6b02627 · 被引用次数：51 · 研究领域：Alzheimer's disease research and treatments、Nanocluster Synthesis and Applications、Nanoparticle-Based Drug Delivery

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.