期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 141, 期 7, 页码 3171-3177出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.8b12820
关键词
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资金
- NSFC/China [21788102, 21421004, 21636002, 21622602, 81522045]
- National Key Research and Development Program [2017YFC0906902, 2016YFA0200300]
- Shanghai Municipal Science and Technology Major Project [2018SHZDZX03]
- Innovation Program of Shanghai Municipal Education Commission, Scientific Committee of Shanghai [15XD1501400]
- Programme of Introducing Talents of Discipline to Universities [B16017]
High-fidelity mapping of amyloid-beta (A beta) plaques is critical for the early detection of Alzheimer's disease. However, in vivo probing of A beta 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 A beta plaques, through introducing a lipophilic pi-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 A beta deposition. Probe QM-FN-SO3 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 A beta plaques with remarkable binding affinity, and serving as an efficient alternative to the commercial probe ThT or ThS.
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