Amyloid-β oligomer targeted theranostic probes for in vivo NIR imaging and inhibition of self-aggregation and amyloid-β induced ROS generation

Xueli Wang, Chengke Wang, Hei Nga Chan, Iyaswamy Ashok, Senthil Kumar Krishnamoorthi, Min LI, Hung Wing Li, Ricky M S WONG*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

To enable the early detection and intervention of Alzheimer's disease (AD), it is highly desirable to develop novel theranostic agents for simultaneous detection of toxic and pathogenic amyloid-β (Aβ) oligomers in vivo and attenuation of Aβ-induced toxicity. Herein, we report a new series of oligomeric Aβ targeted near infrared (NIR) emissive dibutylnaphthylamine-based cyanine probes for in vivo and ex vivo imaging of Aβ in AD mouse model. These new fluorophores exhibited strong solvatochromism and a large bathochromic shift of the emission spectrum upon binding with Aβ species, giving rise to advantageous NIR emission. Besides, they showed an intriguingly stronger fluorescence enhancement upon interacting with Aβ oligomers and monomers, and binding affinity toward Aβ oligomers and monomers than Aβ fibrils, suggesting they were selective to Aβ oligomers and monomers. In addition to low toxicity, one of the fluorophores, DBAN-SLM, showed remarkably effective inhibitory effect on Aβ aggregation, significant neuroprotection effect against the Aβ-induced toxicities, and suppression on Aβ-induced reactive oxygen species (ROS) generation. Because of excellent blood-brain barrier (BBB) permeability, good biocompatibility and stability, high specificity towards Aβ oligomers as well as strong turn-on fluorescence upon Aβ binding, DBAN-SLM was successfully applied for in vivo and ex vivo imaging of Aβ in AD mouse model, signifying its great promise as a useful theranostic agent for the early diagnosis and therapy of AD. Our results also demonstrated for the first time that the dibutyl-2-naphthylamine moiety is a useful and effective structural building block to promote the targeting capability of oligomeric Aβ.

Original languageEnglish
Article number121830
JournalTalanta
Volume224
DOIs
Publication statusPublished - 1 Mar 2021

Scopus Subject Areas

  • Analytical Chemistry

User-Defined Keywords

  • Aggregation inhibitor
  • Alzheimer's disease
  • Amyloid-β oligomer selectivity
  • NIR imaging
  • ROS generation Inhibitor

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