Multifunctional Liposomes Targeting Amyloid-β Oligomers for Early Diagnosis and Therapy of Alzheimer's Disease

Sudipta Senapati, Kuldeep Tripathi, Khadeja Awad, Shai Rahimipour

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
JournalSmall
Early online date10 Mar 2024
DOIs
StateE-pub ahead of print - 10 Mar 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Small published by Wiley-VCH GmbH.

Funding

The authors thank Dr. Anat Haviv‐Chesner for her support in conducting studies, Dr. Michal Richman for assistance with biophysical studies, and Dr. Ronen Yehuda for his contributions to fluorescence imaging. Funding from the Israel Science Foundation (grant No. 2926/21) is gratefully acknowledged. Careful proofreading of the manuscript by Dr. Yuval Elias is appreciated. S.S. acknowledges the Planning and Budgeting Committee, Israel for the postdoctoral fellowship award. C. elegans

FundersFunder number
Israel Science Foundation2926/21

    Keywords

    • Alzheimer's disease
    • Aβ oligomers
    • blood-brain barrier permeability
    • cyclic D,L-α-peptides
    • early diagnosis
    • liposomes

    Fingerprint

    Dive into the research topics of 'Multifunctional Liposomes Targeting Amyloid-β Oligomers for Early Diagnosis and Therapy of Alzheimer's Disease'. Together they form a unique fingerprint.

    Cite this