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
Externally publishedYes

Bibliographical note

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

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)

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