A one-two punch targeting reactive oxygen species and fibril for rescuing Alzheimer’s disease

Jiefei Wang, Ping Shangguan, Xiaoyu Chen, Yong Zhong, Ming Lin, Mu He, Yisheng Liu, Yuan Zhou, Xiaobin Pang, Lulu Han, Mengya Lu, Xiao Wang, Yang Liu, Huiqing Yang, Jingyun Chen, Chenhui Song, Jing Zhang (), Xin Wang (), Bingyang Shi () and Ben Zhong Tang ()
Additional contact information
Jiefei Wang: Academy for Advanced Interdisciplinary Studies, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Ping Shangguan: Academy for Advanced Interdisciplinary Studies, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Xiaoyu Chen: Beijing Institute of Technology
Yong Zhong: School of Materials Science and Engineering, Collaborative Innovation Center of Nano Functional Materials and Applications, Henan University
Ming Lin: Academy for Advanced Interdisciplinary Studies, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Mu He: Academy for Advanced Interdisciplinary Studies, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Yisheng Liu: Academy for Advanced Interdisciplinary Studies, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Yuan Zhou: Academy for Advanced Interdisciplinary Studies, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Xiaobin Pang: Academy for Advanced Interdisciplinary Studies, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Lulu Han: Academy for Advanced Interdisciplinary Studies, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Mengya Lu: Academy for Advanced Interdisciplinary Studies, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Xiao Wang: Academy for Advanced Interdisciplinary Studies, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Yang Liu: Academy for Advanced Interdisciplinary Studies, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Huiqing Yang: Academy for Advanced Interdisciplinary Studies, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Jingyun Chen: Academy for Advanced Interdisciplinary Studies, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Chenhui Song: Academy for Advanced Interdisciplinary Studies, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Jing Zhang: Southern Medical University
Xin Wang: Academy for Advanced Interdisciplinary Studies, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Bingyang Shi: Academy for Advanced Interdisciplinary Studies, Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University
Ben Zhong Tang: Shenzhen Institute of Aggregate Science and Technology, The Chinese University of Hong Kong, Shenzhen

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Toxic amyloid-beta (Aβ) plaque and harmful inflammation are two leading symptoms of Alzheimer’s disease (AD). However, precise AD therapy is unrealizable due to the lack of dual-targeting therapy function, poor BBB penetration, and low imaging sensitivity. Here, we design a near-infrared-II aggregation-induced emission (AIE) nanotheranostic for precise AD therapy. The anti-quenching emission at 1350 nm accurately monitors the in vivo BBB penetration and specifically binding of nanotheranostic with plaques. Triggered by reactive oxygen species (ROS), two encapsulated therapeutic-type AIE molecules are controllably released to activate a self-enhanced therapy program. One specifically inhibits the Aβ fibrils formation, degrades Aβ fibrils, and prevents the reaggregation via multi-competitive interactions that are verified by computational analysis, which further alleviates the inflammation. Another effectively scavenges ROS and inflammation to remodel the cerebral redox balance and enhances the therapy effect, together reversing the neurotoxicity and achieving effective behavioral and cognitive improvements in the female AD mice model.

Date: 2024
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DOI: 10.1038/s41467-024-44737-x

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