Negatively Charged Gold Nanoparticles Inhibit Alzheimer's Amyloid-β Fibrillization, Induce Fibril Dissociation, and Mitigate Neurotoxicity

Amyloids are pathogenic hallmarks in many neurodegenerative diseases such as amyloid‐β (Aβ) fibrils in Alzheimer's disease (AD). Here, the effect of gold nanoparticles (AuNPs) on amyloids is examined using Aβ as a model system. It is found that bare AuNPs inhibited Aβ fibrillization to form fragmented fibrils and spherical oligomers. Adding bare AuNPs to preformed Aβ fibrils results in ragged species where AuNPs bind preferentially to fibrils. Similar results are demonstrated with carboxyl‐ but not amine‐conjugated AuNPs. Co‐incubation of negatively charged AuNPs with Aβ relieved Aβ toxicity to neuroblastoma. Overall, it is demonstrated that AuNPs possessing negative surface potential serve as nano‐chaperones to inhibit and redirect Aβ fibrillization, which could contribute to applications for AD. Negatively charged bare and carboxyl‐conjugated gold nanoparticles, but not positively charged amine‐conjugated gold nanoparticles, inhibit Alzheimer's amyloid‐β (Aβ) fibrillization. The negatively charged gold nanoparticles induce formation of spherical oligomers and short fibrils, whereas the amine‐ conjugated gold nanoparticles do not influence Aβ fibril morphology. Addition of negatively charged gold nanoparticles along with Aβ results in reduction of Aβ‐induced toxicity in human neuroblastoma cells.