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Preparation method and application of multifunctional anti-tumor targeted diagnosis and treatment drug based on gold nanostar

A therapeutic drug, gold nanotechnology, applied in the field of medicine, can solve the problems of high toxic and side effects, poor biocompatibility, poor targeting, etc., and achieve the effects of small toxic and side effects, low cost, and simple preparation process

Inactive Publication Date: 2017-09-22
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0010] In view of the above situation, in order to overcome the defects in the prior art, the purpose of the present invention is to provide a preparation method and application of a multifunctional anti-tumor targeted diagnosis and treatment drug based on gold nanostars, which can effectively solve the toxicity of existing anti-tumor drugs. Large side effects, poor biocompatibility, and poor targeting

Method used

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Examples

Experimental program
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Effect test

Embodiment 1

[0023] In concrete implementation, the present invention can be realized by the following steps:

[0024] (1) Preparation of aminated gold nanostars: at 25°C, under magnetic stirring at 540 r / min, add NH with a weight concentration of 0.5 mg / mL to 20 mL of a gold nanostar solution with a weight concentration of 50 μg / mL 2 - 1 mL of PEG2000-SH solution and 1 mL of PEI-SH solution with a weight concentration of 10 / mg / mL were stirred at room temperature in the dark for 12 hours, centrifuged at 10,000 rpm for 30 minutes at high speed to obtain a precipitate, which was redissolved in 22 mL of ultrapure water to obtain aminated Gold nanostar (GNSTs-PEG / PEI) solution;

[0025] (2) Preparation of gold nanostar solution modified by hydrazine bond: first take 2.54 mg of p-carboxyphenylhydrazine, dissolve it in 0.2 mL of ultrapure water to obtain a carboxylation solution, and then weigh 1-(3-dimethylaminopropyl)- 4.06 mg of 3-ethylcarbodiimide hydrochloride, 1.78 mg of N-hydroxysuccinim...

Embodiment 2

[0029] In specific implementation, the present invention can also be realized by the following steps:

[0030] (1) Preparation of aminated gold nanostars: at 19°C, under magnetic stirring at 700 r / min, add NH with a weight concentration of 5 mg / mL to 15 mL of a gold nanostar solution with a weight concentration of 50 μg / mL 2 - PEG2000-SH 3mL, stirred at room temperature and protected from light for 9 hours, centrifuged at 10,000 rpm for 30 minutes, and redissolved in ultrapure water to obtain aminated gold nanostar (GNSTs-PEG) solution;

[0031] (2) Preparation of gold nanostar solution modified with hydrazine bond: first weigh 3 mg of p-carboxyphenylhydrazine, dissolve it in ultrapure water to obtain a carboxylation solution, and then weigh 1-(3-dimethylaminopropyl)-3- Add 4.5 mg of ethylcarbodiimide hydrochloride, 2 mg of N-hydroxysuccinimide and 1.7 mg of 4-dimethylaminopyridine to 2 mL of dimethyl sulfoxide in sequence, and then add the carboxylation solution to dimethyl s...

Embodiment 3

[0035] In specific implementation, the present invention can also be realized by the following steps:

[0036] (1) Preparation of aminated gold nanostars: At 23°C, under magnetic stirring at 400 r / min, add 4 mL of PEI-SH with a weight concentration of 9 mg / mL to 18 mL of a gold nanostar solution with a weight concentration of 50 μg / mL, and store at room temperature Stir and react in the dark for 10 hours, centrifuge at 10,000 rpm for 30 minutes at high speed, and redissolve with ultrapure water to obtain aminated gold nanostar (GNSTs-PEI) solution;

[0037] (2) Preparation of gold nanostar solution modified with hydrazine bond: first weigh 3.5 mg of p-carboxyphenylhydrazine, dissolve it in ultrapure water to obtain a carboxylation solution, and then weigh 1-(3-dimethylaminopropyl)-3 -Ethylcarbodiimide hydrochloride 4mg, N-hydroxysuccinimide 3mg and 4-dimethylaminopyridine 1.9mg were sequentially added to 2.5mL dimethyl sulfoxide, and then the carboxylation solution was added t...

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Abstract

The present invention relates to the preparation method and application of a multifunctional anti-tumor targeted diagnosis and treatment drug based on gold nanostars, which can effectively solve the problems of existing anti-tumor drugs with large toxic and side effects, poor biocompatibility, and poor targeting. The method is as follows: Structurally modify the gold nanostar carrier, react with an amino compound containing a sulfhydryl group to obtain an amino-modified gold nanostar solution; then perform an amide reaction on the amino-modified gold nanostar with a hydrazine bond compound that activates a carboxyl group to generate a hydrazine-linked terminal bond-modified gold nanostar solution; then use the hydrazine bond at its end to react with carbonyl-containing doxorubicin to form a pH-sensitive hydrazone bond compound; Reaction, that is, the body of the present invention has good physical and chemical stability, simple preparation process, rich source of raw materials, low cost, less toxic and side effects, and can effectively inhibit tumor cell proliferation, which is an innovation in anti-tumor targeted diagnosis and treatment drugs.

Description

technical field [0001] The invention relates to medicine, in particular to a preparation method and application of a multifunctional anti-tumor targeted diagnosis and treatment drug (system) based on gold nanostars. Background technique [0002] Nano-gold / silver uses metal salts of gold and silver as raw materials, and synthesizes nanoscale gold or silver with different properties by controlling experimental conditions. At present, different synthesis methods can be used to synthesize spherical, rod-shaped, star-shaped and other shapes, so that nano-gold / silver has different physical and chemical properties, and its size is generally 10-100 nm. They have the following advantages: (1) The preparation process is simple and the dispersibility is good; (2) The dielectric and photoelectric properties can be adjusted; (3) The surface of the particles can be effectively combined with biomolecules (such as antibodies, hormones, proteins, etc.); ( 4) Good biocompatibility and stabil...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/69A61K47/02A61K41/00A61K49/04A61K31/704A61P35/00A61K47/52
Inventor 王蕾孟德辉郝永伟张潘潘史进进赵亚林李懂张兵详张振中张云
Owner ZHENGZHOU UNIV
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