Rational Design of Near-Infrared Aggregation-Induced-Emission-Active Probes: In Situ Mapping of Amyloid-β Plaques with Ultrasensitivity and High-Fidelity

作者：Wei Fu, Chenxu Yan, Zhiqian Guo, Jingjing Zhang, Haiyan Zhang, He Tian, Weihong Zhu · 发表于：Journal of the American Chemical Society · 年份：2019 · DOI：10.1021/jacs.8b12820 · 被引用次数：446 · 研究领域：Luminescence and Fluorescent Materials、Molecular Sensors and Ion Detection、Supramolecular Self-Assembly in Materials

High-fidelity mapping of amyloid-β (Aβ) plaques is critical for the early detection of Alzheimer’s disease. However, in vivo probing of Aβ plaques by commercially available thioflavin derivatives (ThT or ThS) has proven to be extremely limited, as evident by the restriction of enrichment quenching effect, low signal-to-noise ( S / N ) ratio, and poor blood–brain barrier (BBB) penetrability. Herein, we demonstrate a rational design strategy of near-infrared (NIR) aggregation-induced emission (AIE)-active probes for Aβ plaques, through introducing a lipophilic π-conjugated thiophene-bridge for extension to NIR wavelength range with enhancement of BBB penetrability, and tuning the substituted position of the sulfonate group for guaranteeing specific hydrophilicity to maintain the fluorescence- off state before binding to Aβ deposition. Probe QM-FN-SO 3 has settled well the AIE dilemma between the lipophilic requirement for longer emission and aggregation behavior from water to protein fibrillogenesis, thus making a breakthrough in high-fidelity feedback on in vivo detection of Aβ plaques with remarkable binding affinity, and serving as an efficient alternative to the commercial probe ThT or ThS.