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Rational Design of Near-Infrared AIE-Active Probes: In Situ Mapping of Amyloid-β Plaques with Ultra-Sensitivity and High-Fidelity.

著者 Fu W , Yan C , Guo Z , Zhang J , Zhang H , Tian H , Zhu WH
J Am Chem Soc.2019 Jan 11 ; ():.
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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 commercial-availably 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 lipophilic π-conjugated thiophene-bridge for extending to NIR wavelength with enhancement of BBB penetrability, and tuning the substituted position of sulfonate group for guaranteeing specific hydrophilicity to keep fluorescence-off state before binding to Aβ deposition. Probe QM-FN-SO3 has well settled the AIE dilemma between 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.
PMID: 30632737 [PubMed - as supplied by publisher]
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