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

Chemical Science
Zhenqi LiuXiaogang Qu

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...Continue Reading

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Citations

Feb 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Paolo DogniniFrancesca Giuntini
Apr 22, 2021·Accounts of Chemical Research·Zhi DuXiaogang Qu
May 14, 2021·Journal of Drug Targeting·Qin OuyangQubo Zhu
Jun 20, 2021·Advanced Drug Delivery Reviews·Lingxiao ZhangFangyuan Li
Jul 25, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yaliang HuangJianxiu Wang
Nov 18, 2021·Organic & Biomolecular Chemistry·Youhei SohmaMotomu Kanai

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Methods Mentioned

BETA
nuclear magnetic resonance
dynamic light scattering
circular dichroism
Fluorescence
fluorescence assay
transgenic

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