Inhibition of Amyloid Aggregation and Toxicity with Janus Iron Oxide Nanoparticles
| Autor: | Yuhuan Li, Yanting Xing, Andrew K. Whittaker, Ibrahim Javed, Alon M. Douek, Aleksandr Kakinen, Ruirui Qiao, Kairi Koppel, Changkui Fu, Xulin Wan, Zhiyuan Song, Fangyun Xin, Nicholas Andrikopoulos, Thomas P. Davis, Jan Kaslin, Pu Chun Ke, Yang Song, Feng Ding |
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| Rok vydání: | 2021 |
| Předmět: |
chemistry.chemical_classification
0303 health sciences Reactive oxygen species Amyloid Chemistry General Chemical Engineering 02 engineering and technology General Chemistry 021001 nanoscience & nanotechnology Article 3. Good health 03 medical and health sciences chemistry.chemical_compound Amyloid disease In vivo Materials Chemistry Biophysics Thioflavin Protein folding Viability assay 0210 nano-technology Iron oxide nanoparticles 030304 developmental biology |
| Zdroj: | Chem Mater |
| ISSN: | 1520-5002 0897-4756 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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