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Ultraviolet light-triggered crosslinking near-infrared molecular probe as well as preparation method and application thereof

A molecular probe, near-infrared technology, applied in chemical instruments and methods, medical preparations containing active ingredients, pharmaceutical formulations, etc. Mild triggering conditions and efficient cross-linking reaction

Active Publication Date: 2019-01-11
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although a large number of literatures have reported that the near-infrared fluorescent small molecule probes synthesized based on such dyes can effectively target tumors and be used for tumor imaging and photothermal therapy, but because they are easily eliminated by cell or tissue metabolism, their in vivo The blood circulation cycle is very short, which seriously affects the imaging of tumors and the effect of photothermal therapy

Method used

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  • Ultraviolet light-triggered crosslinking near-infrared molecular probe as well as preparation method and application thereof
  • Ultraviolet light-triggered crosslinking near-infrared molecular probe as well as preparation method and application thereof
  • Ultraviolet light-triggered crosslinking near-infrared molecular probe as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] Example 1: Synthesis and characterization of photocrosslinkable near-infrared molecular probes

[0070] (1) Add propargylamine (0.29 mL), N,N-dimethylformamide (30 mL), HOBt (0.68 g, 5.04 mmol), HBTU (1.91 g, 5.04 mmol) and Diisopropylethylamine (1.08 g, 8.4 mmol) was stirred evenly. Subsequently, N-tert-butoxycarbonyl-N'-fluorenylmethoxycarbonyl-D-lysine (1.97 g, 4.2 mmol) was added into the reaction flask, stirring was continued, and the reaction was carried out at room temperature overnight (20 hours). After the reaction, the solvent was removed by rotary evaporation, and 30 mL of ethyl acetate was added to redissolve the intermediate compound. Then the organic phase was washed once with 30 mL deionized water, saturated sodium bicarbonate and sodium chloride aqueous solution respectively, dried with anhydrous magnesium sulfate and then spin-dried to obtain white powdery intermediate 1 (its structure is as follows: figure 1 Compound 1 in ) (1.95 g, yield: 92%).

[...

Embodiment 2

[0082] Example 2: Photocrosslinking of photocrosslinkable near-infrared molecular probe DACF after ultraviolet light irradiation

[0083] Such as figure 2 As shown, the photocrosslinkable near-infrared molecular probe DACF prepared in Example 1 was diluted into the cell culture medium, and then added to the 4T1 cell culture dish for co-incubation. When the probe enters the tumor cell, it is irradiated with ultraviolet light, and the group carried by the probe will generate an intermediate carbene, which will then be covalently bonded to the surrounding macromolecular proteins through C-H, O-H, N-H and S-H insertion reactions, making the probe The needle molecule is firmly connected with the macromolecular protein in the tumor cell, thereby prolonging the residence time of the probe molecule in the cell and improving the imaging and therapeutic effect of the probe molecule. For the mechanism, please refer to the attached figure 2 .

Embodiment 3

[0084] Example 3: HPLC purity characterization and high-resolution mass spectrometry characterization of photocross-linked near-infrared molecular probe DACF

[0085] After diluting the photocross-linked near-infrared molecular probe prepared in Example 1 to a concentration of 5 μM with solvent methanol, the molecular weight of the probe was determined by high-resolution mass spectrometry, and its purity was determined by high-performance liquid chromatography. analyze.

[0086] Such as image 3 As shown in a, the sample was analyzed by Agilent 1260 high-performance liquid chromatography, and the retention time of the probe DACF was 8.176 minutes. After further integrating the peak area, the concentration of the probe in the sample was calculated as high as 99%. image 3 b shows the theoretical m / z of the probe DACF: 1423.6847, and the m / z in the high-resolution mass spectrum actually obtained: 1423.1622, the two are consistent, which is the desired compound.

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Abstract

The invention discloses an ultraviolet light-triggered croslinking near-infrared molecular probe as well as a preparation method and application of the molecular probe. Particularly, the preparation method comprises the following steps: constructing and synthesizing a photo-crosslinking near-infrared molecular probe DACF; and causing the photo-crosslinking near-infrared molecular probe DACF to crosslink in cells under the triggering of ultraviolet light. The probe is irradiated by light with a specific wavelength to generate a Carbene intermediate with high activity and is bound with an intracellular biomolecule covalent bond, so that the intake of the probe in the cell is remarkably increased, the residence time is prolonged, and the long-term tracking of tumor cells can be realized. Meanwhile, the tumor cells can be well killed by virtue of the photothermal effect of the probe. According to the photo-crosslinking near-infrared molecular probe prepared by virtue of the preparation method, the accumulation amount of the probe in a living tumor can be effectively increased, the residence time can be effectively prolonged, the diagnosis and treatment integration of the tumor is realized, and the molecular probe has important scientific research values and economic values.

Description

technical field [0001] The invention belongs to the technical field of functional modification of near-infrared dyes, and in particular relates to a preparation method for modifying traditional near-infrared dye Cypate by a diaziridine group mediated by ultraviolet light, a molecular probe prepared by the method, and the probe The application of needles in the preparation of near-infrared fluorescence imaging of tumors and anti-tumor drugs based on photothermal therapy (PTT). Background technique [0002] As we all know, organic near-infrared fluorescent dyes have the characteristics of good fluorescence quantum yield, low biological toxicity, plastic molecular structure, and low price, and are widely used in near-infrared biological imaging. [0003] At present, the most common near-infrared dye that has been approved by the FDA for tumor imaging is Indocyanine Green (ICG), which can generate near-infrared fluorescence for near-infrared fluorescence imaging, and can also co...

Claims

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Application Information

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IPC IPC(8): C07D487/04C09B23/08A61K31/519A61P35/00A61K41/00A61K49/00
CPCA61K41/0052A61K49/0034A61P35/00C07D487/04C09B23/086
Inventor 史海斌孙瑞
Owner SUZHOU UNIV
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