Amyloid‑β guided responsive theranostic fluorescent probe for imaging of endogenous hydrogen peroxide in Alzheimer disease

Yuncong Yang, Chengke Wang*, Huanxin Xue, Pinyou Chen, Hung Wing Li*, Man Shing Wong*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

2 Citations (Scopus)

Abstract

Alzheimer disease (AD) is an irreversible and incurable neurodegenerative disorder. Amyloid-β (Aβ), the pathological hallmarks of AD, is known to induce oxidative stress due to the overproduction of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) leading to neurotoxicity and ultimately, neuronal death. Therefore, H2O2 could be a reliable biomarker for more precise detection and diagnosis of AD. Herein, we report the development of highly sensitive and effective ratiometric Aβ-guided H2O2-responsive theranostic probes for sensing and tracking of endogenous H2O2 in AD mouse models. Among the probes synthesized, HY3 was shown to possess superior multifunctional properties including low cytotoxicity and good biocompatibility, strong binding with Aβ and large Aβ binding-induced fluorescence enhancement, excellent H2O2 specificity, superior stability, and of particular importance, rapid response, and high sensitivity toward H2O2 in the presence of Aβ for selective imaging and monitoring of endogenous H2O2 in real time in AD mouse model. Molecular docking revealed the difference in the binding motif and interactions of the probe HY3 and its H2O2-oxidized product, HY2 with Aβ fibrils giving rise to the difference of Aβ binding-induced fluorescence enhancement between them. Impressively, with the promotion of Aβ, HY3 was able to detect the endogenous H2O2 level ratiometrically in AD cell model and differentiate the difference between the normal and AD cells. More importantly, the excellent BBB permeable and biocompatible HY3 probe enabled it to target the senile plaques and serve as an effective and highly sensitive ratiometric fluorescent probe to image and monitor endogenous H2O2 level in vivo in different age groups of AD mice. Furthermore, the inhibitory function against Aβ aggregation of HY2 offers an additional benefit for the therapeutic use of this versatile probe. Our results suggested that H2O2 could be a useful and reliable biomarker for AD and HY3 is a highly promising and effective tool in the detection of Aβ-induced H2O2 level in vivo for more precise diagnosis of AD as well as can serve as a potential pro-drug to treat AD.

Original languageEnglish
Article number135452
JournalSensors and Actuators B: Chemical
Volume406
DOIs
Publication statusPublished - 1 May 2024

Scopus Subject Areas

  • Electronic, Optical and Magnetic Materials
  • Instrumentation
  • Condensed Matter Physics
  • Surfaces, Coatings and Films
  • Metals and Alloys
  • Electrical and Electronic Engineering
  • Materials Chemistry

User-Defined Keywords

  • Alzheimer's disease
  • Aβ-induced enhancement
  • In-vivo imaging
  • Responsive theranostic probe
  • Therapeutic function

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