Citation: Le Chen, Hui Wang, Yiyun Cheng. An erucin-anchored polymer with excellent amyloidosis inhibition and direct cell membrane penetration ability for intracellular protein delivery[J]. Chinese Chemical Letters, ;2026, 37(4): 111172. doi: 10.1016/j.cclet.2025.111172 shu

An erucin-anchored polymer with excellent amyloidosis inhibition and direct cell membrane penetration ability for intracellular protein delivery

Le Chen ^a ,
Hui Wang ^{a, *,} ,
Yiyun Cheng ^{b, *,}

a.
South China Advanced Institute for Soft Matter Science and Technology, School of Emergent Soft Matter, South China University of Technology, Guangzhou 510640, China
b.
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China

wangh@scut.edu.cn

yycheng@mail.ustc.edu.cn

Received Date: 26 January 2025
Revised Date: 29 March 2025
Accepted Date: 1 April 2025
Available Online: 2 April 2025

Figures(5)

Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disorder, marked by a variety of pathological hallmarks such as oxidative stress (OS), metal accumulation, and the aggregation of amyloid-beta (Aβ) proteins. Erucin, a natural compound present in cruciferous plants, has demonstrated promising therapeutic potential in modulating neurodegenerative diseases, hinting at its neuroprotective capabilities. In this study, we engineered an innovative intracellular protein delivery system centered around erucin. This delivery platform operates through a cell membrane perforation mechanism, enabling the swift translocation of target proteins into the cytoplasm. As a result, it substantially shortens the time required for the proteins to exert their functions. Significantly, this delivery system inherently possesses the capacity to inhibit Aβ aggregation. In PC12 cell models, the delivery of the antioxidant enzyme superoxide dismutase (SOD) successfully mitigated the OS triggered by Aβ aggregation and decreased cytotoxicity. This multifaceted therapeutic strategy holds great promise as an effective approach for the treatment of AD.
- Alzheimer's disease,
- Aβ aggregation,
- Protein delivery,
- Rapid translocation,
- Oxidative stress
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