TY - JOUR
T1 - Inhibition of Amyloid Aggregation and Toxicity with Janus Iron Oxide Nanoparticles
AU - Andrikopoulos, Nicholas
AU - Song, Zhiyuan
AU - Wan, Xulin
AU - Douek, Alon M.
AU - Javed, Ibrahim
AU - Fu, Changkui
AU - Xing, Yanting
AU - Xin, Fangyun
AU - Li, Yuhuan
AU - Kakinen, Aleksandr
AU - Koppel, Kairi
AU - Qiao, Ruirui
AU - Whittaker, Andrew K.
AU - Kaslin, Jan
AU - Davis, Thomas P.
AU - Song, Yang
AU - Ding, Feng
AU - Ke, Pu Chun
N1 - Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021/8/24
Y1 - 2021/8/24
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.chemmater.1c01947
DO - 10.1021/acs.chemmater.1c01947
M3 - Article
AN - SCOPUS:85113625869
SN - 0897-4756
VL - 33
SP - 6484
EP - 6500
JO - Chemistry of Materials
JF - Chemistry of Materials
IS - 16
ER -