Abstract
Early detection and treatment are crucial for Alzheimer's disease (AD) management. Current diagnostic and therapeutic methods focus on late-stage amyloid fibrils and plaques, overlooking toxic soluble amyloid β oligomers (AβOs) accumulating early in AD. A multifunctional liposome-based platform is designed for early diagnosis and therapy of AD, leveraging a novel self-assembled cyclic d,l-α-peptide (CP-2) that selectively targets AβOs. Biocompatible CP-2 conjugated liposomes (CP-2-LPs) effectively disrupt Aβ aggregation and mitigate Aβ-mediated toxicity in human neuroblastoma cells. In transgenic Caenorhabditis elegans AD models, CP-2-LPs significantly outperformed free CP-2 by improving cognitive and behavioral functions, extending lifespan, and reducing toxic AβO levels. Intravenous injection of fluorescently labeled CP-2-LPs reveals effective blood-brain barrier penetration, with significantly higher brain fluorescence in transgenic mice than WT, enabling precise diagnosis. These findings underscore CP-2-LPs as a valuable tool for early detection and targeted therapy in AD.
Original language | English (US) |
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Article number | 2311670 |
Journal | Small |
Volume | 20 |
Issue number | 31 |
DOIs | |
State | Published - Aug 1 2024 |
Externally published | Yes |
Keywords
- Alzheimer's disease
- Aβ oligomers
- blood-brain barrier permeability
- cyclic D,L-α-peptides
- early diagnosis
- liposomes
ASJC Scopus subject areas
- Biotechnology
- General Chemistry
- Biomaterials
- General Materials Science
- Engineering (miscellaneous)