Rational Design of Near-Infrared Aggregation-Induced-Emission Active Probes: In Situ Mapping of Annyloid-β Plaques with Ultrasensitivity and High-Fidelity
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- 20 February 2019
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 141 (7), 3171-3177
- https://doi.org/10.1021/jacs.8b12820
Abstract
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.Funding Information
- State Administration of Foreign Experts Affairs (B16017)
- Ministry of Education of the People's Republic of China (B16017)
- Ministry of Science and Technology of the People's Republic of China (2016YFA0200300, 2017YFC0906902)
- Shanghai Municipal Education Commission
- Science and Technology Commission of Shanghai Municipality (15XD1501400)
- National Natural Science Foundation of China (21636002, 21622602, 21421004, 21788102, 81522045)
- Shanghai Municipality (2018SHZDZX03)
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