Characterizing the Effect of Multivalent Conjugates Composed of Aβ-Specific Ligands and Metal Nanoparticles on Neurotoxic Fibrillar Aggregation
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- 作者：Carmen Streich ; Laura Akkari ; Christina Decker ; Jenny Bormann ; Christoph Rehbock ; Andreas Müller-Schiffmann ; Felix Carlsson Niemeyer ; Luitgard Nagel-Steger ; Dieter Willbold ; Barbara Sacca ; Carsten Korth ; Thomas Schrader ; Stephan Barcikowski
- 刊名：ACS Nano
- 出版年：2016
- 出版时间：August 23, 2016
- 年：2016
- 卷：10
- 期：8
- 页码：7582-7597
- 全文大小：857K
- 年卷期：0
- ISSN：1936-086X
文摘
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.