TY - JOUR
T1 - Effective Theranostic Cyanine for Imaging of Amyloid Species in Vivo and Cognitive Improvements in Mouse Model
AU - Li, Yinhui
AU - Chen, Chen
AU - Xu, Di
AU - Poon, Chung Yan
AU - Ho, See Lok
AU - Zheng, Rui
AU - Liu, Qiong
AU - Song, Guoli
AU - Li, Hung Wing
AU - Wong, Man Shing
N1 - Funding Information:
This work was supported by the Health and Medical Research Fund (HMRF 01122066) from the Hong Kong Government, and Collaborative Research Fund of Hong Kong Research Grant Council (C2012-15G). We are also thankful for the support of the National Natural Sciences Foundation of China (nos 81400847 and 21675135).
PY - 2018/6/30
Y1 - 2018/6/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85049106098&partnerID=8YFLogxK
U2 - 10.1021/acsomega.8b00475
DO - 10.1021/acsomega.8b00475
M3 - Journal article
AN - SCOPUS:85049106098
SN - 2470-1343
VL - 3
SP - 6812
EP - 6819
JO - ACS Omega
JF - ACS Omega
IS - 6
ER -