Mitigating Human IAPP Amyloidogenesis In Vivo with Chiral Silica Nanoribbons

Ava Faridi, Yunxiang Sun, Yutaka Okazaki, Guotao Peng, Jie Gao, Aleksandr Kakinen, Pouya Faridi, Mei Zhao, Ibrahim Javed, Anthony W Purcell, Thomas P Davis, Sijie Lin, Reiko Oda, Feng Ding, Pu Chun Ke

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13 Citations (Scopus)

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.

Original languageEnglish
Article number1802825
Number of pages13
JournalSmall
Volume14
Issue number47
DOIs
Publication statusPublished - 22 Nov 2018

Keywords

  • amyloidogenesis
  • chirality
  • human IAPP
  • silica nanoribbons
  • toxicity

Cite this

Faridi, A., Sun, Y., Okazaki, Y., Peng, G., Gao, J., Kakinen, A., Faridi, P., Zhao, M., Javed, I., Purcell, A. W., Davis, T. P., Lin, S., Oda, R., Ding, F., & Ke , P. C. (2018). Mitigating Human IAPP Amyloidogenesis In Vivo with Chiral Silica Nanoribbons. Small, 14(47), [1802825]. https://doi.org/10.1002/smll.201802825