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

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.