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Heptamethine indole cyanine dye-polyethylene glycol-folic acid compound and its preparation method and application

A technology of heptamethanindocyanine and polyethylene glycol is applied in the detection of lung cancer cells, in the field of preparation of heptamethanindocyanine dye-polyethylene glycol-folate, which can solve the problems of vascular toxicity and liver and kidney toxicity. , protein denaturation and other problems, to achieve the effect of improving water solubility, reducing toxic and side effects, and mild preparation process conditions

Active Publication Date: 2018-12-11
ARMY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

And DMSO is a kind of hydrogen bond breaking agent, which has serious toxic effect, and interacts with protein hydrophobic groups, leading to protein denaturation, has vascular toxicity and liver and kidney toxicity; Toxic substances dissolved in it are brought into the skin, so there is a potential safety risk when applying

Method used

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  • Heptamethine indole cyanine dye-polyethylene glycol-folic acid compound and its preparation method and application
  • Heptamethine indole cyanine dye-polyethylene glycol-folic acid compound and its preparation method and application
  • Heptamethine indole cyanine dye-polyethylene glycol-folic acid compound and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Example 1. Preparation of IR808-PEG (step a)

[0041] According to the molar ratio of 1:1:1.3:1, weigh heptamethine indole cyanine dye IR-808 (see the above reaction formula for its structure), amino-terminated PEG (molecular weight 3400), N,N'-dicyclohexyl carbon After imide and N-hydroxysuccinimide are placed in a dry Erlenmeyer flask, the volumes of dichloromethane, tetrahydrofuran, and N,N-dimethylformamide are successively measured to be 15mL, 3mL, and 3mL as the reaction mixture. Solvent, filled with argon for 1-2min, sealed, protected from light, at room temperature, and kept stirring for 12-48h;

Embodiment 2

[0042] Embodiment 2. Preparation of folic acid active ester (FA-NHS) (step b)

[0043] According to the molar ratio of 1:1.2:1.1, weigh folic acid (FA), N,N'-dicyclohexyl carboximide and N-hydroxysuccinimide in a dry Erlenmeyer flask, then measure dichloro Methane, tetrahydrofuran, N,N-dimethylformamide 15mL, 3mL, 3mL as a mixed solvent for the reaction, sealed and protected from light, room temperature, and continuously stirred for 12-24h; the product obtained is folic acid active ester FA-NHS.

Embodiment 3

[0044] Example 3. Preparation of IR-808-PEG-FA (step c)

[0045] Fully mix the IR-808-PEG obtained from the reaction in Example 1 with folic acid active ester (FA-NHS), pass through argon for 1-2 minutes, seal, keep away from light, keep stirring for 24-72 hours, remove the precipitate by high-speed centrifugation, and rotate to evaporate Purify by chromatography after removing the organic solvent, the eluent composition ratio V 二氯甲烷 :V 甲醇 =20:1-0:1, collect the last eluted part to prepare the target product IR-808-PEG-FA. Using deuterated chloroform as the solvent nuclear magnetic resonance spectrum to determine the structure of the product, the results are as follows: figure 1 Shown; Take PBS (pH=7.4) as the fluorescence property of solvent detection product, the result is as follows figure 2 shown.

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Abstract

The invention relates to a heptamethine indocyanine dye-polyethylene glycol-folate compound, as well as a preparation method and application thereof. The heptamethine indocyanine dye-polyethylene glycol-folate can be used for improving the universal problem of lipid solubility of small-molecular near infrared fluorescent dyes and enhancing the target specificity of related tissues. The method is mild in reaction conditions, simple in steps, easy to operate and low in raw material cost. The heptamethine indocyanine dye-polyethylene glycol-folate compound prepared by the method has good water solubility and high application safety, and is beneficial to reduction of toxicity on normal cells; and the heptamethine indocyanine dye-polyethylene glycol-folate has targeting performance on lung cancer with a high expression folate receptor.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to a preparation method of heptamethine indole cyanine dye-polyethylene glycol-folic acid and a method for detecting lung cancer cells highly expressing folic acid receptors. Background technique [0002] Fluorescence imaging has unique advantages in medical and biological research, where the near-infrared region (600nm-1000nm) is detected due to the lowest light absorption and the weakest autofluorescence of biomolecules, and a large amount of infrared light can penetrate tissues and skin . Due to the high sensitivity of the near-infrared region, which can provide real-time dynamic imaging of tumors in vivo, in recent years, near-infrared in vivo imaging technology has attracted more and more attention from scholars and surgeons. [0003] In near-infrared fluorescence imaging, the quality of fluorescent probes is crucial. Among the near-infrared small-molecule fluorescent...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/00C08G65/337C08G65/333
CPCA61K49/0034A61K49/0054C08G65/33396C08G65/337
Inventor 罗圣霖王素军史春梦
Owner ARMY MEDICAL UNIV