Mitigating Human IAPP Amyloidogenesis In Vivo with Chiral Silica Nanoribbons. Issue 47 (7th October 2018)

• Record Type: Journal Article
• Authors: Faridi, Ava; Sun, Yunxiang; Okazaki, Yutaka; Peng, Guotao; Gao, Jie; Kakinen, Aleksandr; Faridi, Pouya; Zhao, Mei; Javed, Ibrahim; Purcell, Anthony W.; Davis, Thomas P.; Lin, Sijie; Oda, Reiko; Ding, Feng; Ke, Pu Chun
• Is Part Of: Small. Volume 14:Issue 47(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-10-07
• Subjects: amyloidogenesis -- chirality -- human IAPP -- silica nanoribbons -- toxicity; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.201802825
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: Amyloid fibrils generally display chirality, a feature which has rarely been exploited in the development of therapeutics against amyloid diseases. This study reports, for the first time, the use of mesoscopic chiral silica nanoribbons against the in vivo amyloidogenesis of human islet amyloid polypeptide (IAPP), the peptide whose aggregation is implicated in type 2 diabetes. The thioflavin T assay and transmission electron microscopy show accelerated IAPP fibrillization through elimination of the nucleation phase and shortening of the elongation phase by the nanostructures. Coarse‐grained simulations offer complementary molecular insights into the acceleration of amyloid aggregation through their nonspecific binding and directional seeding with the nanostructures. This accelerated IAPP fibrillization translates to reduced toxicity, especially for the right‐handed silica nanoribbons, as revealed by cell viability, helium ion microscopy, as well as zebrafish embryo survival, developmental, and behavioral assays. This study has implicated the potential of employing chiral nanotechnologies against the mesoscopic enantioselectivity of amyloid proteins and their associated diseases. Abstract : Silica nanoribbons rescue the toxicity of oppositely handed amyloid protein, islet amyloid polypeptide, in an embryonic zebrafish model, pointing to the potential of exploiting nanoscale chirality against amyloidogenesis.