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; Ben Zhong Tang

doi:10.1038/s41467-024-44737-x

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^*, Ben Zhong Tang^*

^*Corresponding author for this work

Macquarie Medical School

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	705
Pages (from-to)	1-16
Number of pages	16
Journal	Nature Communications
Volume	15
Issue number	1
Early online date	24 Jan 2024
DOIs	https://doi.org/10.1038/s41467-024-44737-x
Publication status	Published - Dec 2024

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Copyright the Author(s) 2024. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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Wang, J., Shangguan, P., Chen, X., Zhong, Y., Lin, M., He, M., Liu, Y., Zhou, Y., Pang, X., Han, L., Lu, M., Wang, X., Liu, Y., Yang, H., Chen, J., Song, C., Zhang, J., Wang, X., Shi, B., & Tang, B. Z. (2024). A one-two punch targeting reactive oxygen species and fibril for rescuing Alzheimer’s disease. Nature Communications, 15(1), 1-16. Article 705. https://doi.org/10.1038/s41467-024-44737-x

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title = "A one-two punch targeting reactive oxygen species and fibril for rescuing Alzheimer{\textquoteright}s disease",

abstract = "Toxic amyloid-beta (Aβ) plaque and harmful inflammation are two leading symptoms of Alzheimer{\textquoteright}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.",

author = "Jiefei Wang and Ping Shangguan and Xiaoyu Chen and Yong Zhong and Ming Lin and Mu He and Yisheng Liu and Yuan Zhou and Xiaobin Pang and Lulu Han and Mengya Lu and Xiao Wang and Yang Liu and Huiqing Yang and Jingyun Chen and Chenhui Song and Jing Zhang and Xin Wang and Bingyang Shi and Tang, \{Ben Zhong\}",

note = "Copyright the Author(s) 2024. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2024",

month = dec,

doi = "10.1038/s41467-024-44737-x",

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Wang, J, Shangguan, P, Chen, X, Zhong, Y, Lin, M, He, M, Liu, Y, Zhou, Y, Pang, X, Han, L, Lu, M, Wang, X, Liu, Y, Yang, H, Chen, J, Song, C, Zhang, J, Wang, X, Shi, B & Tang, BZ 2024, 'A one-two punch targeting reactive oxygen species and fibril for rescuing Alzheimer’s disease', Nature Communications, vol. 15, no. 1, 705, pp. 1-16. https://doi.org/10.1038/s41467-024-44737-x

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AU - Lin, Ming

AU - He, Mu

AU - Liu, Yisheng

AU - Zhou, Yuan

AU - Pang, Xiaobin

AU - Han, Lulu

AU - Lu, Mengya

AU - Wang, Xiao

AU - Liu, Yang

AU - Yang, Huiqing

AU - Chen, Jingyun

AU - Song, Chenhui

AU - Zhang, Jing

AU - Wang, Xin

AU - Shi, Bingyang

AU - Tang, Ben Zhong

N1 - Copyright the Author(s) 2024. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2024/12

Y1 - 2024/12

N2 - 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.

AB - 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.

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JF - Nature Communications

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ER -

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

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