Preparation method of CT nano contrast agent namely low-algebraic tree-shaped macromolecule-coated gold nano particles with liver cancer targeting function

A technology of dendritic macromolecules and nano-contrast agents, which can be used in the preparation of X-ray contrast agents, medical preparations of non-active ingredients, pharmaceutical formulations, etc., and can solve the problems of undiscovered CT imaging applications, etc.

Inactive Publication Date: 2015-01-07
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 a

Method used

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  • Preparation method of CT nano contrast agent namely low-algebraic tree-shaped macromolecule-coated gold nano particles with liver cancer targeting function
  • Preparation method of CT nano contrast agent namely low-algebraic tree-shaped macromolecule-coated gold nano particles with liver cancer targeting function
  • Preparation method of CT nano contrast agent namely low-algebraic tree-shaped macromolecule-coated gold nano particles with liver cancer targeting function

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

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

[0066] (2) 32.25 mg of lactobionic acid was dissolved in 3.75 mL of disodium hydrogen phosphate-sodium dihydrogen phosphate b...

Embodiment 2

[0069] 34.63 mg of fluorescein isothiocyanate-labeled and lactobionic acid-modified pegylated dendrimer was dissolved in 6.00 mL of distilled water. Then, 211.89 μL (30 mg / mL) of an aqueous chloroauric acid solution was added with 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 resulting solution was dialyzed against distilled water (6 times, 2 L / time) for 3 days. Freeze-drying was then carried out to obtain the final product, which was stored at -20°C. The UV-Vis test results show that there is an absorption peak at about 510nm in the spectrogram (attached figure 2 ), which is the superposition of the surface plasmon resonance peak of nano-gold and the absorption peak of fluorescein, which indicates that gold nanoparticles were successfully prepared in the system. TEM test results show that: the prepared gold nanoparticles ...

Embodiment 3

[0071] Configure the aqueous solution (0.5 mg / mL) of the product obtained in Example 2, place it at different temperatures for half an hour, measure its ultraviolet spectrum, and determine the stability of the product at different temperatures. Find, under different temperature (4-50 ℃) condition, the ultraviolet spectrum of the obtained product of embodiment 2 does not have obvious shift and change, shows that it has good stability (attachment 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, carry out the ultraviolet test. The UV spectra of this product under different pH values ​​(5.0-8.0) have not been shifted and changed due to particle agglomeration through 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, in particular to a method for preparing gold nanoparticles wrapped with low-algebra dendrimers with liver cancer targeting function as CT nano-contrast agents. Background technique [0002] Computed Tomography (CT) utilizes the different transmittances of different tissues of the human body to X-rays to image the internal bones and tissues of the human body. It has high spatial resolution, overall imaging, and image acquisition time. Short, relatively economical and other advantages. In order to increase the discrimination between target tissue and normal tissue, contrast agent is needed to highlight the lesion. Currently, CT contrast agents widely used in clinical practice are mainly iodine-containing small molecular compounds (such as diatrizoic acid, iohexol, etc.). Because the kidney has a rapid elimination effect on iodine-containing small molecule contrast agents, iodine...

Claims

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Application Information

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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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