Abstract
We report herein an investigation of carbazole-based cyanine, (E)-4-(2-(9-(2-(2-methoxyethoxy)ethyl)-9H-carbazol-3-yl)-vinyl)-1-methyl-quinolin-1-iumiodide (SLM), as an effective theranostic agent for Alzheimer’s disease (AD). This cyanine exhibited desirable multifunctional and biological properties, including amyloid-β (Aβ)-oligomerization inhibition, blood–brain barrier permeability, low neurotoxicity, neuroprotective effect against Aβ-induced toxicities, high selectivity and strong binding interactions with Aβ peptide/species, good biostability, as well as strong fluorescence enhancement upon binding to Aβ species for diagnosis and therapy of AD. This cyanine has been successfully applied to perform near-infrared in vivo imaging of Aβ species in transgenic AD mouse model. The triple transgenic AD mice intraperitoneally treated with SLM showed significant recovery of cognitive deficits. Furthermore, those SLM-treated mice exhibited a substantial decrease in both of oligomeric Aβ contents and tau proteins in their brain, which was attributed to the induction of autophagic flux. These findings demonstrated for the first time that SLM is an effective theranostic agent with in vivo efficacy for diagnosis and treatment of AD in mouse models.
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