Plasmonic nanoparticle amyloid corona for screening A beta oligomeric aggregate-degrading drugs

Abstract

The generation of toxic amyloid beta (A beta) oligomers is a central feature of the onset and progression of Alzheimer's disease (AD). Drug discoveries for A beta oligomer degradation have been hampered by the difficulty of A beta oligomer purification and a lack of screening tools. Here, we report a plasmonic nanoparticle amyloid corona (PNAC) for quantifying the efficacy of A beta oligomeric aggregate-degrading drugs. Our strategy is to monitor the drug-induced degradation of oligomeric aggregates by analyzing the colorimetric responses of PNACs. To test our strategy, we use A beta -degrading proteases (protease XIV and MMP-9) and subsequently various small-molecule substances that have shown benefits in the treatment of AD. We demonstrate that this strategy with PNAC can identify effective drugs for eliminating oligomeric aggregates. Thus, this approach presents an appealing opportunity to reduce attrition problems in drug discovery for AD treatment. Effective screening of drugs to treat amyloid oligomeric aggregates associated with Alzheimer's is needed for drug development. Here the authors report on the creation of an amyloid corona around a plasmonic nanoparticle to monitor amyloid degradation when exposed to potential drugs and demonstrate application.