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Peptide‐Modified Mo Polyoxometalate Nanoparticles Suppress Zn 2+ ‐Induced Aβ Aggregation
Author(s) -
Liu Yanan,
Sun Jing,
Gong Youcong,
Zhou Hui,
Chen Xu,
Zhu Xufeng,
Zhao Yingyu,
Wen Yayu,
Qin Xiuying,
Liu Jie
Publication year - 2019
Publication title -
chemnanomat
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 32
ISSN - 2199-692X
DOI - 10.1002/cnma.201900057
Subject(s) - polyoxometalate , peptide , chemistry , nanoparticle , intracellular , biophysics , biochemistry , nanotechnology , materials science , biology , catalysis
The abnormal metabolism of amyloid‐β (Aβ) peptide, as one of the main components of senile plaques, plays a vital role in the pathogenesis of Alzheimer's disease (AD). Our previous work showed that polyoxometalates (POMs) that inhibited the formation of Aβ aggregates were promising for AD therapy. Here, peptide‐modified Mo polyoxometalate (Mo‐POMs) nanoparticles were synthesized by the self‐assembly of Aβ target peptide and Mo‐POMs based on our previous work. Importantly, after modifying with the Aβ target peptide, the Mo polyoxometalate (Mo‐POMs) nanoparticles exhibited enhanced blood‐brain barrier (BBB) penetration and high binding affinity with Aβ species. The interactions between the Peptide@Mo‐POMs nanoparticle and Aβ in the presence of Zn 2+ were comprehensively studied using physicochemical methods (spectroscopy, ThT fluorescence, turbidity tests). Peptide@Mo‐POMs could suppress Aβ aggregation, disaggregate Aβ fibrils, and suppress Zn 2+ ‐induced Aβ aggregation. In addition, in vitro cell experiments revealed that Peptide@Mo‐POMs could target and be well absorbed by PC12 cells, leading to the inhibition of intracellular Aβ aggregation and reduced Aβ aggregates‐induced cytotoxicity. The blood‐brain barrier (BBB) permeability of Peptide@Mo‐POMs was also revealed by the Transwell experiment. This study gives a mechanistic understanding into how Peptide@Mo‐POMs can work through a synergistic interaction with metal ions and Aβ, and provides new insights into the design and synthesis of POMs as Aβ inhibitors in the treatment of AD.