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Preparation method of low-algebraic dendrimer-wrapped gold nanoparticles with liver cancer targeting function as CT nanocontrast agent

A technology of dendrimer and gold nanoparticles, which is used in the preparation of X-ray contrast agents, medical preparations with non-active ingredients, and pharmaceutical formulations, which can solve the problems of undiscovered CT imaging applications.

Inactive Publication Date: 2017-03-29
DONGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] A search of domestic and foreign literature and patents on the use of gold nanoparticles for CT imaging found that: before the completion of the present invention, no fluorescein-labeled and lactobionic acid-modified PEGylated second-generation dendrimer-wrapped gold nanoparticles have been found. Related reports on the preparation of particles and their application in CT imaging

Method used

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  • Preparation method of low-algebraic dendrimer-wrapped gold nanoparticles with liver cancer targeting function as CT nanocontrast agent
  • Preparation method of low-algebraic dendrimer-wrapped gold nanoparticles with liver cancer targeting function as CT nanocontrast agent
  • Preparation method of low-algebraic dendrimer-wrapped gold nanoparticles with liver cancer targeting function as CT nanocontrast agent

Examples

Experimental program
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Effect test

Embodiment 1

[0065] (1) The second generation polyamide-amine dendrimer (G2.NH 2 ) 16.28 mg was dissolved in 3.2 mL of dimethyl sulfoxide, and 17.04 mL of fluorescein isothiocyanate (0.4 mg / mL) in dimethyl sulfoxide was added while stirring. Reaction at room temperature for 24 hours, the reaction solution was dialyzed, distilled water (6 times, 2L / time), dialyzed for 3 days. Then freeze-dried to obtain the dendrimer modified with fluorescein isothiocyanate, and stored at -20°C. 1 The H NMR test results show that the chemical shift peaks at 2.0-3.7 ppm and 6.3-8.0 ppm in the spectrum correspond to the characteristic peaks of dendrimer and fluorescein isothiocyanate, respectively. Calculated from the integral area, each dendrimer is modified with about 2.5 fluorescein isothiocyanate molecules (attached figure 1 a).

[0066] (2) 32.25mg lactobionic acid was dissolved in 3.75mL disodium hydrogen phosphate-sodium dihydrogen phosphate buffer (pH=6.0, 0.02M), and 17.25mg 1-(3-dimethylaminopropyl)-3 ...

Embodiment 2

[0069] 34.63 mg of PEGylated dendrimer labeled with fluorescein isothiocyanate and modified with lactobionic acid was dissolved in 6.00 mL of distilled water. Subsequently, 211.89 μL (30 mg / mL) of the chloroauric acid aqueous solution was added while stirring. After magnetic stirring for 10 min, 291.94 μL (10 mg / mL) of sodium borohydride solution pretreated in an ice bath was added and reacted at room temperature for 3 h. After the reaction, the obtained solution was dialyzed with distilled water (6 times, 2L / time), and dialyzed for 3 days. Then it is freeze-dried to obtain the final product and stored at -20°C. UV-Vis test results show that there is an absorption peak around 510nm in the spectrum (attached figure 2 ), which is the superposition of the surface plasmon resonance peak of gold nanoparticles and the absorption peak of fluorescein, which indicates that gold nanoparticles were successfully prepared in the system. The TEM test results show that the prepared gold na...

Embodiment 3

[0071] The product aqueous solution (0.5 mg / mL) obtained in Example 2 was configured and placed at different temperatures for half an hour, and then the ultraviolet spectrum was measured to determine the stability of the product at different temperatures. It was found that under different temperature (4-50°C) conditions, the UV spectrum of the product obtained in Example 2 did not significantly shift or change, indicating that it has good stability (attached image 3 ).

[0072] The product obtained in Example 2 was prepared as a 0.5 mg / mL aqueous solution, and its pH value (5.0, 6.0, 7.0, 8.0) was adjusted with 0.1 M hydrochloric acid or sodium hydroxide. After standing at room temperature for 20 minutes, UV test was performed. The UV spectra of the product under different pH values ​​(5.0-8.0) have not been shifted or changed due to particle agglomeration after comparative analysis, indicating that it has good stability (attached) Figure 4 ).

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Abstract

The invention relates to a preparation method of a CT nano contrast agent namely low-algebraic tree-shaped macromolecule-coated gold nano particles with a liver cancer targeting function. The preparation method comprises the following steps: dissolving LA-PEG-COOH into a solvent, adding EDC to activate the LA-PEG-COOH for 4 to 6 hours, dropwise adding the solution into a G2-FITC solution, stirring to carry out reactions, performing dialysis, and freeze-drying so as to obtain G2-FITC-PEG-LA; dissolving G2-FITC-PEG-LA into distilled water, adding a chloroauric acid water solution, stirring for 10 to 20 minutes, then adding a NaBH4 water solution, stirring to carry out reactions for 2 to 3 hours, performing dialysis, and freeze-drying so as to obtain the target product. The raw materials are cheap, and the gold nano particles which are prepared by taking a low-algebraic tree-shaped macromolecule as the template, has excellent stability and bio-compatibility. The in-vivo blood circulation time of the gold nano particles is prolonged, and moreover the gold nano particles have a specific targeting function on liver cancer cells, so the gold nano particles are advantageously used in the early-stage tumor detection.

Description

Technical field [0001] The invention belongs to the field of preparation of nano-contrast agents, and in particular relates to a method for preparing a CT nano-contrast agent as a CT nano-contrast agent, with gold nano-particles wrapped by low-generation dendrimers with liver cancer targeting function. Background technique [0002] Computed Tomography (CT) uses the difference in X-ray transmittance of different tissues of the human body to image the internal bones and tissues of the human body, with high spatial resolution, overall imaging, and image acquisition time Short, relatively economical and other advantages. In order to increase the discrimination between the target tissue and the normal tissue, a contrast agent is needed to highlight the lesion. At present, CT contrast agents that are widely used clinically are mainly iodine-containing small molecule compounds (such as diatrizoic acid, iohexol, etc.). Because the kidney has a rapid elimination effect on iodine-contain...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/04A61K47/34
Inventor 史向阳曹已芸刘辉夏进东何瑶
Owner DONGHUA UNIV
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