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

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

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.

Keywords: Aggregation inhibitor; Alzheimer's disease; Amyloid-β oligomer selectivity; NIR imaging; ROS generation Inhibitor.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33379048/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.