journal article·2018-02-27

Tau-Targeted Multifunctional Nanocomposite for Combinational Therapy of Alzheimer’s Disease

Qing Chen, Yang Du, Kai Zhang, Zeyu Liang, Jinquan Li, Hao Yu, Rong Ren, Jin Feng, Zhiming Jin, Fangyuan Li, Jihong Sun, Min Zhou, Qinggang He, Xiaolian Sun, Hong Zhang, Mei Tian, Daishun Ling

ACS Nano· Volume 12· Issue 2
Publisher page

Abstract

Alzheimer's disease (AD) remains an incurable disease and lacks efficient diagnostic methods. Most AD treatments have focused on amyloid-β (Aβ) targeted therapy; however, it is time to consider the alternative theranostics due to accumulated findings of weak correlation between Aβ deposition and cognition, as well as the failures of Phase III clinical trial on Aβ targeted therapy. Recent studies have shown that the tau pathway is closely associated with clinical development of AD symptoms, which might be a potential therapeutic target. We herein construct a methylene blue (MB, a tau aggregation inhibitor) loaded nanocomposite (CeNC/IONC/MSN-T807), which not only possesses high binding affinity to hyperphosphorylated tau but also inhibits multiple key pathways of tau-associated AD pathogenesis. We demonstrate that these nanocomposites can relieve the AD symptoms by mitigating mitochondrial oxidative stress, suppressing tau hyperphosphorylation, and preventing neuronal death both in vitro and in vivo. The memory deficits of AD rats are significantly rescued upon treatment with MB loaded CeNC/IONC/MSN-T807. Our results indicate that hyperphosphorylated tau-targeted multifunctional nanocomposites could be a promising therapeutic candidate for Alzheimer's disease.
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Research context

OpenAlex topics: Alzheimer's disease research and treatments · Cholinesterase and Neurodegenerative Diseases · Nanocluster Synthesis and Applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Nuclear Medicine and PET/CT Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China

Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P.R. China

College of Chemical & Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, P.R. China

Jiangsu Huayi Technology Limited Company, Changshu, Jiangsu 215522, P.R. China

Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China

Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China

Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, Maryland 20892, United States

Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, P.R. China

Funding

Ministry of Education of the People's Republic of China · Ministry of Science and Technology of the People's Republic of China · National Natural Science Foundation of China · Central People's Government of the People's Republic of China

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