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A gold nano-assembly with enhanced tumor radiotherapy and its preparation method and application

A technology of tumor radiotherapy and gold nanotechnology, which is applied in the field of biomedicine, can solve the problems that nanoparticles are not easy to clear the viscera, and it is difficult to reach the deep part of the tumor, and achieve excellent radiosensitivity and stability, small size, and improved cycle time. Effect

Active Publication Date: 2021-10-19
UNIV OF SCI & TECH OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

On the other hand, small-sized nanoparticles can penetrate deep into the tumor, but are easily cleared by the kidneys; large-sized nanoparticles are not easy to be cleared by organs, but it is difficult to reach the deep tumor

Method used

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  • A gold nano-assembly with enhanced tumor radiotherapy and its preparation method and application
  • A gold nano-assembly with enhanced tumor radiotherapy and its preparation method and application
  • A gold nano-assembly with enhanced tumor radiotherapy and its preparation method and application

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Experimental program
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Effect test

Embodiment 1

[0055] The synthesis of embodiment 1, block copolymer PAEMA-b-PEAL:

[0056] (1) First prepare 2-(hexamethyleneimine) ethyl methacrylate, namely AEMA:

[0057] Specifically, 6.4 g of acryloyl chloride was added dropwise to a mixed THF solution of 10.1 g of 2-(hexamethylenediimine) ethanol and 7.0 g of triethylamine in an ice bath environment, and reacted overnight. After the reaction, the triethylamine salt produced in the reaction system was removed by filtration, then concentrated by rotary evaporation, and vacuumed overnight to obtain a colorless transparent liquid product with a yield of 65.7%.

[0058] (2) Second, synthesize lipoic acid hydroxyethyl methacrylate, namely EAL:

[0059] Under room temperature, 2g lipoic acid and 1.6g hydroxyethyl methacrylate were dissolved in dichloromethane, and 0.5g lutidine and 3.9g 1-(3-dimethylaminopropyl)-3-ethyl Carbodiimide, reaction 48h. After the reaction, it was washed successively with hydrochloric acid, saturated sodium bica...

Embodiment 2

[0068] The synthesis of embodiment 2 block copolymer PAEMA-b-mPEG:

[0069] (1) First prepare mPEG-CPAD, polyethylene glycol-4-cyano-4-(thiobenzoyl)valerate:

[0070] Specifically, dicyclohexylcarbodiimide, 4-dimethylaminopyridine, and 4-cyano-4-(thiobenzoyl)valeric acid were dissolved in dichloromethane. After stirring and reacting for 12 hours, it was precipitated with glacial ether to obtain a pink solid with a grafting rate of 75%.

[0071] (2) Preparation of PAEMA-b-mPEG:

[0072] Specifically, 0.051g mPEG-CPAD, 3.2g 2-(hexamethyleneimine) ethyl methacrylate, and 0.003g azobisisobutylcyanide were dissolved in dioxane, and reacted at 75°C under nitrogen atmosphere 12h. After the reaction was completed, it was concentrated under reduced pressure, precipitated with n-hexane, and vacuumed overnight to obtain a pink solid with a yield of 62.6% and a degree of polymerization of 97.

[0073]

[0074] The prepared compound was characterized by proton nuclear magnetic reson...

Embodiment 3

[0075] Example 3, the synthesis of poly 2-cyclohexyl methacrylate block lipoic acid hydroxyethyl methacrylate, namely PCMA-b-PEAL:

[0076] (1) at first prepare 2-cyclohexyl methacrylate, i.e. CMA,:

[0077] Specifically, under the condition of 0° C., methacryloyl chloride was added dropwise into a tetrahydrofuran solution of triethylamine and 2-cyclohexyl ethanol. After reacting overnight, after the reaction was completed, it was filtered, concentrated by rotary evaporation, and then purified by distillation under reduced pressure to finally obtain a colorless transparent liquid with a yield of 53.2%.

[0078] (2) secondly prepare poly 2-cyclohexyl methacrylate, i.e. PCMA:

[0079] Specifically, 0.034 g of cyanomethyl dodecyl trithiocarbonate, 1.95 g of 2-cyclohexyl methacrylate and 0.005 g of azobisisobutylcyanide are uniformly mixed in a dioxane solvent. Under freezing pumping and nitrogen atmosphere, react at 75°C for 12h. After the reaction, it was concentrated under r...

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Abstract

The invention provides a gold nanometer assembly for sensitizing tumor radiotherapy and its preparation method and application. The gold nanometer assembly has pH responsiveness and high permeability at tumor sites. The gold nano assembly is a core-shell structure, the core is gold nanoparticles, and the shell is poly 2-(hexamethyleneimine) ethyl methacrylate block polyethylene glycol, poly 2-(hexamethyleneimine) Ethyl Methacrylate Block Lipoic Acid Hydroxyethyl Methacrylate. Gold has a high absorption coefficient for X-rays and has the function of sensitizing radiotherapy. Polyethylene glycol has good biocompatibility and can improve the circulation time of gold nanoassemblies in blood. 2-(hexamethyleneimine) has pH responsive properties, which makes the size of the gold nano-assembly smaller, and it is easier to penetrate into the deep part of the tumor, further enhancing the lethality of radiotherapy on tumor cells. The gold nanometer assembly prepared by the invention has excellent radiotherapy sensitization and stability, and is beneficial to its application in biomedicine.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a gold nano-assembly with enhanced tumor radiotherapy and its preparation method and application. Background technique [0002] Tumor is a disease in which the accumulation of mutated genes due to its own cell lesions leads to the infinite proliferation of cancer cells and the invasion of normal tissues and organs. According to research, more than 10 million patients worldwide are diagnosed with cancer every year, and more than 8 million patients die due to lack of timely treatment. Statistics in 2019 show that in 2015, there were about 4 million new cases of malignant tumors in my country, and more than 2 million deaths. [0003] Radiation therapy is a common tumor treatment method, which causes DNA damage of tumor cells by generating reactive oxygen species, and then causes their growth to stagnate or die. Due to the abnormal metabolism of tumors compared with normal cells, the tum...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K33/242A61K9/51A61K47/34A61K47/32A61P35/00B22F9/24A61K41/00
CPCB22F9/16A61K33/242A61K9/5146A61K9/5138A61P35/00C08F293/00B82Y30/00B82Y40/00B82Y5/00B22F2009/165B22F1/16
Inventor 王育才黄忠凯王立
Owner UNIV OF SCI & TECH OF CHINA