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

• Published in: Nature communications 2024-01, Vol.15 (1), p.705-16, Article 705
• Main Authors: Wang, Jiefei, Shangguan, Ping, Chen, Xiaoyu, Zhong, Yong, Lin, Ming, He, Mu, Liu, Yisheng, Zhou, Yuan, Pang, Xiaobin, Han, Lulu, Lu, Mengya, Wang, Xiao, Liu, Yang, Yang, Huiqing, Chen, Jingyun, Song, Chenhui, Zhang, Jing, Wang, Xin, Shi, Bingyang, Tang, Ben Zhong
• Format: Article
• Language: English
• Subjects: 14/19; 14/34; 631/1647/245/2225; 639/638/298/54; 692/617/375/365/1283; Alzheimer's disease; Biocompatibility; Blood-brain barrier; Cognitive ability; Computational neuroscience; Emission; Emissions; Fibrillogenesis; Humanities and Social Sciences; I.R. radiation; Inflammation; Medical imaging; multidisciplinary; Near infrared radiation; Neurodegenerative diseases; Neuroimaging; Neurotoxicity; Oxygen; Reactive oxygen species; Science; Science (multidisciplinary); Sensitivity; Signs and symptoms; Therapy; Toxic diseases; β-Amyloid
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-44737-x

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. Toxic amyloid-beta plaque and harmful inflammation are two leading hallmarks of Alzheimer’s disease (AD), and precise AD therapy is elusive due to the lack of dual-targeting therapy function, limited blood-brain barrier penetration, and low imaging sensitivity. Here, the authors address these issues by designing a near-infrared-II aggregation-induced emission nanotheranostic for precise AD therapy.