Gold nanoparticles as amyloid-like fibrillogenesis inhibitors.
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.
Department of Chemistry and Center for Nanoscience and Nanotechnology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan, ROC. Electronic address: shsieh@facmail.nsysu.edu.tw.
Shuchen
S
Hsieh
Chiung-wen
CW
Chang
Hsuan-hung
HH
Chou
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000648:ultrastructure; D000818:Animals; D001812:Blood-Brain Barrier; D002417:Cattle; D002942:Circular Dichroism; D016503:Drug Delivery Systems; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007328:Insulin / Q000737:chemistry; D053768:Metal Nanoparticles / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D055503:Protein Multimerization / Q000187:drug effects
D000682:Amyloid; D007328:Insulin; D006046:Gold
AFM; Alzheimer's; Amyloid fibril; Insulin; Nanoparticle