Gold nanoparticles as amyloid-like fibrillogenesis inhibitors

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 112; pp. 525 - 529
• Main Authors: Hsieh, Shuchen, Chang, Chiung-wen, Chou, Hsuan-hung
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2013
• Subjects: AFM; Alzheimer disease; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer's; amyloid; Amyloid - antagonists & inhibitors; Amyloid - chemistry; Amyloid - ultrastructure; Amyloid fibril; amyloidosis; Animals; Blood-Brain Barrier; Brain; Cattle; Circular Dichroism; colloids; Diseases; Drug Delivery Systems; Gold; Gold - chemistry; Humans; hypoglycemic agents; Inhibitors; Insulin; Insulin - chemistry; insulin resistance; Metal Nanoparticles - chemistry; Microscopy, Atomic Force; Microscopy, Electron, Transmission; nanogold; Nanoparticle; Nanoparticles; Nanostructure; patients; Protein Multimerization - drug effects; therapeutics; AFM; Amyloid fibril; Nanoparticle; Insulin; Alzheimer's
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2013.08.029

•Nanoparticles can cross blood-brain-barrier and target amyloidogenic structures.•AuNPs affect the protein structure and dynamics of insulin fibril for aggregation.•AuNPs delayed amyloid-like fibrils formation by about 1 week.•AuNPs disrupt fibrillogenesis resulting in fibrils are shorter and more compact. Amyloid aggregates are one of the likely key factors leading to the development of Alzheimer's disease (AD) and other amyloidosis associated diseases. Several recent studies have shown that some anti-diabetic drugs have a positive therapeutic effect on AD patients by crossing the blood brain barrier (BBB) and preventing or reducing insulin resistance. Nanoparticles (NPs) or nanoscale objects (<600Da.), are able to cross the BBB at low concentrations, and can specifically target amyloidogenic structures. Thus, NPs are fast becoming indispensable tools for directed drug delivery, particularly when targeting structures or regions in the brain. Here, we have explored the inhibitory effect of gold nanoparticles (AuNPs) on the fibrillogenesis process of insulin fibrils. We found that when AuNPs were co-incubated with insulin, the structural transformation into amyloid-like fibrils was delayed by about a week. Further, the fibrils that formed, exhibited altered structure, shape, and dynamics, which further reduced fibril growth, and the stability of available amyloid-like fibrils with cross-β structure for aggregation. Our results demonstrate that AuNPs disrupt insulin amyloid fibrillation resulting in fibrils that are shorter and more compact, and thus may serve a useful role in new therapeutic and diagnostic strategies for amyloid-related disorders.