Issue 3, 2023

In vivo visualization of enantioselective targeting of amyloid and improvement of cognitive function by clickable chiral metallohelices

Abstract

The pathogenesis of Alzheimer's disease (AD) is closely related to several contributing factors, especially amyloid-β (Aβ) aggregation. Bioorthogonal reactions provide a general, facile, and robust route for the localization and derivatization of Aβ-targeted agents. Herein, a pair of chiral alkyne-containing metallohelices (ΛA and ΔA) were demonstrated to enantioselectively target and modulate Aβ aggregation, which has been monitored in triple-transgenic AD model mice and proved to improve cognitive function. Compared with its enantiomer ΔA, ΛA performed better in blocking Aβ fibrillation, relieving Aβ-triggered toxicity, and recovering memory deficits in vivo. Moreover, clickable ΛA could act as a functional module for subsequent visualization and versatile modification of amyloid via bioorthogonal reaction. As a proof-of-concept, thioflavin T, tacrine, and magnetic nanoparticles were conjugated with ΛA to realize Aβ photo-oxygenation, acetylcholinesterase inhibition, and Aβ clearance, respectively. This proof-of-principle work provided new insights into the biolabeling and bioconjugation of multifunctional metallosupramolecules through click reactions for AD therapy.

Graphical abstract: In vivo visualization of enantioselective targeting of amyloid and improvement of cognitive function by clickable chiral metallohelices

Supplementary files

Article information

Article type
Edge Article
Submitted
25 Oct 2022
Accepted
26 Nov 2022
First published
28 Nov 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 506-513

In vivo visualization of enantioselective targeting of amyloid and improvement of cognitive function by clickable chiral metallohelices

Z. Du, C. Liu, Z. Liu, H. Song, P. Scott, X. Du, J. Ren and X. Qu, Chem. Sci., 2023, 14, 506 DOI: 10.1039/D2SC05897A

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