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Near-infrared A beta fluorescence imaging agent with high signal-noise ratio, as well as preparation method and application thereof

A high signal-to-noise ratio, fluorescence imaging technology, applied in the direction of fluorescence/phosphorescence, chemical instruments and methods, preparations for in vivo experiments, etc.

Inactive Publication Date: 2018-12-21
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Aiming at the bottleneck problem existing in the existing Aβ fluorescence imaging technology, the present invention provides a kind of Aβ fluorescence imaging agent based on aggregation-induced emission (aggregation-induced emission, AIE) near-infrared and high signal-to-noise ratio

Method used

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  • Near-infrared A beta fluorescence imaging agent with high signal-noise ratio, as well as preparation method and application thereof
  • Near-infrared A beta fluorescence imaging agent with high signal-noise ratio, as well as preparation method and application thereof
  • Near-infrared A beta fluorescence imaging agent with high signal-noise ratio, as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] (1) Synthesis of dye I-1:

[0042]

[0043] In a 100mL round-bottom flask, add 1-ethyl-2-methyl-4-(α,α-dicyano)methylene-1,4-dihydroquinoline (116.4mg, 0.50mmol), 5-(N,N-Dimethylaniline)-2-thiophenealdehyde (104mg, 0.50mmol) and 30mL of toluene were added dropwise to 0.5mL of ammonium acetate solution (2M), and reacted at 150°C for 2h under argon protection. After cooling to room temperature, the toluene was removed by rotary evaporation, and the column chromatography was separated (200-300 mesh silica gel, PE:CH 2 Cl 2 =5:2), the red solid 50mg was obtained by rotary evaporation, and the yield was 38%.

[0044] 1 H NMR(400MHz, DMSO-d 6 ,ppm)δ=1.42(t,J=8.0Hz,3H,NCH 2 CH 3 -H),δ=2.97(s,6H,CH 3 -H),δ=4.54(q,J=8.0Hz,2H,NCH 2 CH 3 -H),δ=6.77(d,J=8.0Hz,2H,Ph-H),δ=7.03(s,1H,Ph-H),δ=7.07(d,J=16Hz,1H,alkene-H ),δ=7.38(d,J=4.0Hz,1H,Ph-H),δ=7.54(d,2H,J=4.0Hz,thiophene-H),δ=7.57(s,1H,Ph-H) ,7.62(t,J=8.0Hz,1H,Ph-H),δ=7.66(d,J=16Hz,1H,alkene-H),7.93(t,J=4.0Hz,1H,Ph-H), δ = 8.09 (d, J ...

Embodiment 2

[0052] The absorption and fluorescence spectra of dye I-2 in the aggregate state

[0053] Take the dye I-2 prepared in Example 1 and dissolve it in analytically pure dimethyl sulfoxide to make 1.0×10 -3 M stock solution. Then prepare EtOH / H with 95% ethanol (EtOH) 2 O mixed solvent 2mL. Take 20μL of the above stock solution and add it to the prepared EtOH / H 2 In the O mixed solvent, mix evenly and transfer to an optical quartz cuvette (10×10mm) to test its fluorescence spectrum. Such as figure 2 As shown, with 500nm as the excitation wavelength, the maximum emission peak of dye 1-2 is located at about 720nm in the near-infrared region, and the Stokes shift reaches 200nm; and the aggregation of dye 1-2 in the mixed solvent leads to its fluorescence enhancement, which has Typical concentrated fluorescence enhancement characteristics.

Embodiment 3

[0055] Dye I-2 to Aβ 42 Fiber's spectral response

[0056] Take the dye I-2 prepared in Example 1 and dissolve it in analytically pure dimethyl sulfoxide to make 1.0×10 -3 M stock solution. Then prepare 2.91 mL of PBS buffer. Take 3μL of the above stock solution and add it to the prepared PBS buffer, then add 90μL Aβ 42 Fiber storage solution (1×10 -4 M). The mixed solution was incubated at 37°C for 30 minutes, mixed evenly, and transferred to an optical quartz cuvette (10×10 mm) to test its absorption and fluorescence spectra. Such as Figure 4 As shown, Aβ is not added 42 When fiber, dye I-2 basically has no fluorescence signal; when adding Aβ 42 After fiber, using 500nm as the excitation wavelength, the maximum emission peak appears at 660nm in the near-infrared region, and the fluorescence intensity increases by about 50 times, showing an extremely high signal-to-noise ratio.

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Abstract

The invention provides a near-infrared A beta fluorescence imaging agent with high signal-noise ratio, as well as a preparation method and application thereof. An aggregation-induced emission dye hasa structure as shown in the formula I. In addition, the invention also provides application of the A beta fluorescence imaging agent in brain tissue slice fluorescent marking and living imaging. The tests show that the aggregation-induced emission dye provided by the invention has the advantages of near-infrared emission, high light stability, good biocompatibility, high signal-noise ratio and thelike, and can be used for accurately positioning an A beta plaque in an APP / PS1 transgenic mice brain tissue slice, so that the in-situ information such as the number of A beta plaques and real-timeform is acquired in a high fidelity way. Particularly, the imaging agent has favorable blood-brain barrier penetrability, and can be applied to in-vivo real-time imaging of the APP / PS1 transgenic micebrain A beta plaque. The formula I is shown in the description.

Description

Technical field [0001] The invention belongs to the technical field of fine chemicals, and specifically relates to a type of Aβ fluorescent imaging agent based on near-infrared and high signal-to-noise ratio, a preparation method thereof, and a fluorescent labeling application on brain tissue slices. Background technique [0002] Alzheimer's disease (AD) is a neurodegenerative disease and one of the main causes of Alzheimer's disease. So far, there is still no clinically tested drug that has a significant effect on it, so Alzheimer's disease (AD) is considered an incurable disease. Studies have shown that the formation and deposition of Aβ plaques in the brain plays an extremely important role in the neuropathology of AD, and is considered a biomarker for early diagnosis and prediction of the disease. Therefore, the development of high-performance Aβ plaque imaging agents is of great significance for the early diagnosis and treatment of Alzheimer's disease. [0003] Fluorescence ...

Claims

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Application Information

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IPC IPC(8): C07D409/06C09K11/06A61K49/00A61P25/28G01N21/64
CPCA61K49/0021A61P25/28C07D409/06C09K11/06C09K2211/1007C09K2211/1029C09K2211/1092G01N21/6428G01N21/6486G01N2021/6439
Inventor 郭志前朱为宏付伟燕宸旭顾开智石丽敏毛文乐马一宇
Owner EAST CHINA UNIV OF SCI & TECH
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