PUBLICATION

Inhibition of Amyloid Aggregation and Toxicity with Janus Iron Oxide Nanoparticles

Authors
Andrikopoulos, N., Song, Z., Wan, X., Douek, A.M., Javed, I., Fu, C., Xing, Y., Xin, F., Li, Y., Kakinen, A., Koppel, K., Qiao, R., Whittaker, A.K., Kaslin, J., Davis, T.P., Song, Y., Ding, F., Ke, P.C.
ID
ZDB-PUB-211214-30
Date
2021
Source
Chemistry of materials : a publication of the American Chemical Society   33: 6484-6500 (Journal)
Registered Authors
Douek, Alon M., Kaslin, Jan
Keywords
Amyloid beta, IAPP, Janus nanoparticle, alpha synuclein, iron oxide nanoparticle
MeSH Terms
none
PubMed
34887621 Full text @ Chem Mater
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 beta casein-coated iron oxide nanoparticles (βCas IONPs) via a 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 beta (Aβ), alpha 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 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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping