Volume 44, Issue 23 2300378
Research Article

Self-Destructive Nanoscavengers Capture and Clear Neurotoxic Soluble β-Amyloid Aggregates

Yu Zhao

Corresponding Author

Yu Zhao

Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University, Tianjin, 300071 China

Department of Biomedical Engineering, Tufts University, Medford, MA, 02155 USA

E-mail: [email protected]; [email protected]

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Qiushi Li

Qiushi Li

Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University, Tianjin, 300071 China

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Qingqing Huang

Qingqing Huang

Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University, Tianjin, 300071 China

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Yang Liu

Corresponding Author

Yang Liu

Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University, Tianjin, 300071 China

Frontiers Science Center for New Organic Matter, Nankai University, Tianjin, 300071 China

State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071 China

E-mail: [email protected]; [email protected]

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First published: 03 August 2023

Abstract

Cerebral soluble β-amyloid aggregates (sAβs) accumulation is one of the most important causes in Alzheimer's disease (AD) progression. In order to mitigate the neurotoxicity induced by sAβs and achieve enhanced AD therapeutic outcomes, robust sAβs clearance become an emerging task. Herein, a self-destructive nanoscavenger (SDNS) is reported based on multifunctional peptide-polymer complexes that can capture extracellular sAβs via hydrogen-bonding interactions and deliver them into microglial lysosomes. The internalized SDNS then occurs self-destruction within lysosomes and upregulates autophagy, thereby promoting the degradation of neurotoxic sAβs. Importantly, the enhanced autophagy also significantly suppresses the secretion of inflammatory factors by microglia, which is induced by internalized sAβs. Given that cerebral persistent inflammatory environment disturbs microglia-mediated phagocytosis and degradation, it is believed that this synergistic approach has valuable potential as a therapeutic strategy for AD.

Conflict of Interest

The authors declare no conflict of interest.

Data Availability Statement

The data that support the findings of this study are available in the supplementary material of this article.

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