Inhibition of Amyloid Aggregation and Toxicity with Janus Iron Oxide Nanoparticles

Nicholas Andrikopoulos, Zhiyuan Song, Xulin Wan, Alon M. Douek, Ibrahim Javed, Changkui Fu, Yanting Xing, Fangyun Xin, Yuhuan Li, Aleksandr Kakinen, Kairi Koppel, Ruirui Qiao, Andrew K. Whittaker, Jan Kaslin, Thomas P. Davis, Yang Song, Feng Ding, Pu Chun Ke

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Amyloid aggregation is a ubiquitous form of protein misfolding underlying the pathologies of Alzheimer's disease (AD), Parkinson's disease (PD), and type 2 diabetes (T2D), three primary forms of human amyloid diseases. While much has been learned about the origin, diagnosis, and management of these neurological and metabolic disorders, no cure is currently available due in part to the dynamic and heterogeneous nature of the toxic oligomers induced by amyloid aggregation. Here, we synthesized β-casein-coated iron oxide nanoparticles (βCas IONPs) via a 2-(bis-((phosphonic acid)methyl)amino)ethyl-(poly(oligo ethylene glycol)methyl ether acrylate)-b-(poly(N-ethyl-2,3-dibromomaleimide)acrylate)-((butylthio)-carbonothioyl)thio propionate (BPA-P(OEGA-b-DBM)) block copolymer linker. Using a thioflavin T kinetic assay, transmission electron microscopy, Fourier transform infrared spectroscopy, discrete molecular dynamics simulations, and cell viability assays, we examined the Janus characteristics and the inhibition potential of βCas IONPs against the aggregation of amyloid β (Aβ), α synuclein (αS), and human islet amyloid polypeptide (IAPP), which are implicated in the pathologies of AD, PD, and T2D. Incubation of zebrafish embryos with the amyloid proteins largely inhibited hatching and elicited reactive oxygen species, which were effectively rescued by the inhibitor. Furthermore, Aβ-induced damage to the mouse brain was mitigated in vivo with the inhibitor. This study revealed the potential of Janus nanoparticles as a new nanomedicine against a diverse range of amyloid diseases.

Original languageEnglish (US)
Pages (from-to)6484-6500
Number of pages17
JournalChemistry of Materials
Volume33
Issue number16
DOIs
StatePublished - Aug 24 2021
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Chemical Engineering
  • Materials Chemistry

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