Plasmonic nanoparticle amyloid corona for screening Aβ oligomeric aggregate-degrading drugs

• Published in: Nature communications Vol. 12; no. 1; pp. 639 - 11
• Main Authors: Lee, Dongtak, Park, Dongsung, Kim, Insu, Lee, Sang Won, Lee, Wonseok, Hwang, Kyo Seon, Lee, Jeong Hoon, Lee, Gyudo, Yoon, Dae Sung
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 27.01.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Aggregates; Alzheimer's disease; Amyloid; Amyloid - chemistry; Amyloid beta-Peptides - chemistry; Colorimetry; Degradation; Drug development; Drug screening; Drugs; Gelatinase B; Gold - chemistry; Kinetics; Ligands; Metal Nanoparticles - chemistry; Metal Nanoparticles - ultrastructure; Nanoparticles; Neurodegenerative diseases; Oligomers; Plasmonics; Protein Aggregates; Strategy; Time Factors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-20611-4

The generation of toxic amyloid β (Aβ) oligomers is a central feature of the onset and progression of Alzheimer's disease (AD). Drug discoveries for Aβ oligomer degradation have been hampered by the difficulty of Aβ oligomer purification and a lack of screening tools. Here, we report a plasmonic nanoparticle amyloid corona (PNAC) for quantifying the efficacy of Aβ 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 Aβ-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.