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Issue 40, 2020
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Target-driven supramolecular self-assembly for selective amyloid-β photooxygenation against Alzheimer's disease

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Abstract

Photo-oxygenation of β-amyloid (Aβ) has been considered an efficient way to inhibit Aβ aggregation in Alzheimer's disease (AD). However, current photosensitizers cannot simultaneously achieve enhanced blood–brain barrier (BBB) permeability and selective photooxygenation of Aβ, leading to poor therapeutic efficacy, severe off-target toxicity, and substandard bioavailability. Herein, an Aβ target-driven supramolecular self-assembly (PKNPs) with enhanced BBB penetrability and switchable photoactivity is designed and demonstrated to be effective in preventing Aβ aggregation in vivo. PKNPs are prepared by the self-assembly of the Aβ-targeting peptide KLVFF and an FDA-approved porphyrin derivative (5-(4-carboxyphenyl)-10,15,20-triphenylporphyrin). Due to the photothermal effect of PKNPs, the BBB permeability of PKNPs under irradiation is 8.5-fold higher than that of porphyrin alone. Moreover, upon selective interaction with Aβ, PKNPs undergo morphological change from the spherical to the amorphous form, resulting in a smart transformation from photothermal activity to photodynamic activity. Consequently, the disassembled PKNPs can selectively oxygenate Aβ without affecting off-target proteins (insulin, bovine serum albumin, and human serum albumin). The well-designed PKNPs exhibit not only improved BBB permeability but also highly selective Aβ photooxygenation. Furthermore, in vivo experiments demonstrate that PKNPs can alleviate Aβ-induced neurotoxicity and prolong the life span of the commonly used AD transgenic Caenorhabditis elegans CL2006. Our work may open a new path for using supramolecular self-assemblies as switchable phototheranostics for the selective and effective prevention of Aβ aggregation and related neurotoxicity in AD.

Graphical abstract: Target-driven supramolecular self-assembly for selective amyloid-β photooxygenation against Alzheimer's disease

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Supplementary files

Article information


Submitted
09 Sep 2020
Accepted
06 Oct 2020
First published
06 Oct 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020,11, 11003-11008
Article type
Edge Article

Target-driven supramolecular self-assembly for selective amyloid-β photooxygenation against Alzheimer's disease

Z. Liu, M. Ma, D. Yu, J. Ren and X. Qu, Chem. Sci., 2020, 11, 11003
DOI: 10.1039/D0SC04984K

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    [Original citation] - Published by The Royal Society of Chemistry.

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