Design of Self-Assembled Nanoparticles as a Potent Inhibitor and Fluorescent Probe for β-Amyloid Fibrillization

Alzheimer's disease (AD) remains incurable due to its complex pathogenesis. The deposition of β-amyloid (Aβ) in the brain appears much earlier than any clinical symptoms and plays an essential role in the occurrence and development of AD neuropathology, which implies the importance of early the...

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Publié dans:Langmuir : the ACS journal of surfaces and colloids. - 1985. - 39(2023), 36 vom: 12. Sept., Seite 12576-12589
Auteur principal: Wang, Ying (Auteur)
Autres auteurs: Liu, Wei, Dong, Xiaoyan, Sun, Yan
Format: Article en ligne
Langue:English
Publié: 2023
Accès à la collection:Langmuir : the ACS journal of surfaces and colloids
Sujets:Journal Article Research Support, Non-U.S. Gov't Amyloid beta-Peptides Fluorescent Dyes Amyloidogenic Proteins
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520 |a Alzheimer's disease (AD) remains incurable due to its complex pathogenesis. The deposition of β-amyloid (Aβ) in the brain appears much earlier than any clinical symptoms and plays an essential role in the occurrence and development of AD neuropathology, which implies the importance of early theranostics. Herein, we designed a self-assembled bifunctional nanoparticle (LC8-pCG-fLC8) for Aβ fluorescent diagnosis and inhibition. The nanoparticle was synthesized by click chemistry from Aβ-targeting peptide Ac-LVFFARKC-NH2 (LC8) and an Aβ fluorescent probe f with the zwitterionic copolymer poly(carboxybetaine methacrylate-glycidyl methacrylate) (p(CBMA-GMA), pCG). Owing to the high reactivity of epoxy groups, the peptide concentration of LC8-pCG-fLC8 nanoparticles reached about 4 times higher than that of the existing inhibitor LVFFARKpoly(carboxybetaine) (LK7@pCB). LC8-pCG-fLC8 exhibited remarkable inhibitory capability (suppression efficiency of 83.0% at 20 μM), altered the aggregation pathway of Aβ, and increased the survival rate of amyloid-induced cultured cells from 76.5% to 98.0% at 20 μM. Notably, LC8-pCG-fLC8 possessed excellent binding affinity, good biostability, and high fluorescence responsivity to β-sheet-rich Aβ oligomers and fibrils, which could be used for the early diagnosis of Aβ aggregation. More importantly, in vivo tests using transgenic C. elegans CL2006 stain showed that LC8-pCG-fLC8 could specifically image Aβ plaques, prolong the lifespan (from 13 to 17 days), and attenuate the AD-like symptoms (reducing paralysis and Aβ deposition). Therefore, self-assembled nanoparticles hold great potential in AD theranostics 
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700 1 |a Liu, Wei  |e verfasserin  |4 aut 
700 1 |a Dong, Xiaoyan  |e verfasserin  |4 aut 
700 1 |a Sun, Yan  |e verfasserin  |4 aut 
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