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Nanoprobe for photoacoustic rate bioassay of hydrogen sulfide, and manufacture method and application thereof

A technology of living body detection and nano-probe, which is applied in the field of tumor marker detection and imaging

Inactive Publication Date: 2018-08-28
SOUTH CHINA NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] At present, the most commonly used methods for detection and imaging of hydrogen sulfide are the methylene blue method and the sulfur ion selective electrode detection method. Their disadvantages are that both are destructive and require homogenization of samples. For the study of more detailed physiological functions of hydrogen sulfide , new detection methods are needed With the rapid development of non-destructive detection technologies such as fluorescent imaging fluorescent probes, many novel detection methods have emerged [a) Li, H.D.; Yao, Q.C.; Fan, J.L.; Jiang, N. ; Wang, J.Y.; Xia, J.; Peng, X.J.Chem.Commun.2015, 51, 16225-16228.b) C.Liu, J.Pan, S.Li, Y.Zhao, L.Y.Wu, C.E.Berkman, A.R. Whorton and M.Xian, Angew.Chem., IntEd., 2011, 50, 10327–10329c) H.Peng, Y.Cheng, C.Dai, A.L.King, B.L.Predmore, D.J.Lefer and B.Wang, Angew.Chem ., Int. Ed., 2011, 50, 9672–9675d) K. Sasakura, K. Hanaoka, N. Shibuya, Y. Mikami, Y. Kimura, T. Komatsu, T. Ueno, T. Terai, H. Kimura and T. Nagano, J. Am. Chem. Soc. 2011, 133, 18003–18005]
[0004] The main disadvantage of this type of method is that in live detection, the scattering of ultrasonic signals by biological tissues to physiological tissues of the human body is 3 to 4 orders of magnitude lower than that of general optical signals, which means that photoacoustic imaging can provide deeper imaging depth and higher imaging resolution

Method used

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  • Nanoprobe for photoacoustic rate bioassay of hydrogen sulfide, and manufacture method and application thereof
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  • Nanoprobe for photoacoustic rate bioassay of hydrogen sulfide, and manufacture method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0093] Example 1: Preparation of a photoacoustic ratiometric probe for in vivo detection of intratumoral hydrogen sulfide.

[0094] 1. The specific synthesis steps of a photoacoustic ratiometric probe for intratumoral hydrogen sulfide detection provided by the present invention are as follows: figure 1 As shown, the details are as follows:

[0095] (1) Preparation of ①I precursor: Dissolve m-aminophenol (436mg, 4mmol) in 13ml of absolute ethanol, tert-butyl dicarbonate (1.3g, 6mmol) in 5ml of absolute ethanol and add dropwise, stir for 5 Minutes, refluxed at 80°C for 5h, the solution was concentrated in vacuo to obtain white solid A.

[0096] ②Add white solid A (81.9mg, 0.39mmol) and sodium hydride (9.36mg, 0.39mmol) into a round bottom flask filled with 2ml of DMF (N,N-dimethylformamide), and the mixture is stirred at room temperature under nitrogen protection 10min, Cy7-Cl (100mg, 0.156mmol) was dissolved in 1ml DMF and added to the above-mentioned round bottom flask, stir...

Embodiment 2

[0117] Embodiment 2: the absorption before and after the reaction of probe I and sodium hydrosulfide, fluorescence spectrum.

[0118] Configure the probe I solution and sodium hydrosulfide aqueous solution obtained in Example 1, then mix the probe I solution and sodium hydrogensulfide aqueous solution for five minutes and measure its absorption; wherein, the concentration of probe I in the reaction system is 10 μM, The concentration of sodium hydrosulfide was 50 μM. Absorption spectrum such as Figure 6 As shown, the fluorescence spectrum as Figure 7 As shown, it can be seen from the figure that the probe has a fluorescent response before and after reacting with sodium hydrosulfide.

Embodiment 3

[0119] Example 3: Photoacoustic imaging and ratiometric imaging of probe I reacted with different concentrations of sodium hydrosulfide.

[0120] A total of 6 groups of probe Ⅰ solutions with a concentration of 20 μM and aqueous sodium sulfide solutions with a concentration of 0, 20, 40, 60, 80, and 100 μM were prepared, and then the probe Ⅰ solution was mixed with the aqueous sodium sulfide solution for reaction (probe The consumption of Ⅰ solution is 40 μ l, the consumption of sodium hydrosulfide aqueous solution is 1, 2, 3, 4, 5 μ l respectively), after each group reacts for 5 minutes respectively, measure the photoacoustic signal of 6 groups of solutions with photoacoustic computed tomography scanner, and the photoacoustic two-dimensional map ( Figure 8 ). It can be seen from the figure that the intensity of the photoacoustic signal at 532nm gradually decreases with the increase of the concentration, and the intensity of the photoacoustic signal at 700nm gradually increa...

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Abstract

The invention discloses a nanoprobe for photoacoustic rate bioassay of hydrogen sulfide, and a manufacture method and application thereof. The structural formula of the nanoprobe is shown as the formula I. The manufacture method of the nanoprobe mainly includes subjecting a raw material, Cy7-Cl, to nucleophilic substitution, knoevenagel condensation and amino azide reaction to obtain the nanoprobe. The problems of scattering and tissue absorption of fluorescence signals of fluorescence probes in bioassay are solved; the prepared nanoprobe has the advantages of high photoacoustic-signal penetration depth, imaging of deep tissues, high response speed, high specificity and high rate detection accuracy, and can be applied to bioassay of the hydrogen sulfide, or detection of the hydrogen sulfide in water and food. The formula I is shown in the specification.

Description

technical field [0001] The invention belongs to the field of tumor marker detection and imaging, and in particular relates to a photoacoustic ratio nanoprobe for detecting hydrogen sulfide in a living body, a preparation method and application thereof. Background technique [0002] Hydrogen sulfide is a toxic gas with the smell of rotten eggs. Hydrogen sulfide is the third biosynthetic gas transmitter after nitric oxide and carbon monoxide. Hydrogen sulfide plays an important role in many biological processes, such as blood vessels Relaxation of smooth muscle, regulation of neurotransmission, regulation of insulin signaling, inhibition of inflammation, sensing of oxygen, etc.; it also has a protective effect on the heart and nerves in the human body, and is an effective neuromodulatory substance, H 2 Physiologically relevant concentrations of S range from nanomolar to millimolar levels. At physiological concentrations, H 2 S is involved in a series of physiological regulat...

Claims

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Application Information

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IPC IPC(8): C07D405/06C09K11/06G01N21/17
Inventor 张涛邢达马腾
Owner SOUTH CHINA NORMAL UNIVERSITY
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