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Chlorotoxin-targeted oxidized graphene nanometer material used for transporting antitumor drug

A nano-material and graphene technology, applied in the direction of anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., can solve the problems of limited effectiveness, DOX cannot pass through the blood-brain barrier, and achieve the effect of reducing side effects

Inactive Publication Date: 2014-03-12
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

DOX has limited utility in glioma therapy due to its inability to cross the blood-brain barrier and unwelcome side effects

Method used

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  • Chlorotoxin-targeted oxidized graphene nanometer material used for transporting antitumor drug
  • Chlorotoxin-targeted oxidized graphene nanometer material used for transporting antitumor drug
  • Chlorotoxin-targeted oxidized graphene nanometer material used for transporting antitumor drug

Examples

Experimental program
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Effect test

preparation example Construction

[0054] The method for preparing CTX-targeted graphene oxide nanomaterials for anti-tumor drug transport provided by the present invention first oxidizes graphite into graphene oxide, obtains a large number of carboxyl groups on its surface, and then couples CTX to graphite oxide through EDC activation CTX-targeted graphene oxide nanomaterials for antitumor drug delivery.

[0055] Specifically, its main steps are:

[0056] 1) Mix 5g graphite, 100mL H 2 SO 4 -HClO 4 The mixture was placed in an ice bath, stirred for 1 h to make it fully mixed, placed in an ice bath for 24 h, moved into a warm water bath at 40°C and continued to stir for 24 hours. Heat at 120°C for 4 hours to remove the acid, dilute the reaction solution with distilled water to 800-1000ml, centrifuge, then add an appropriate amount of 0.1mNaOH to mix and stir at 90°C for 2 hours, filter while hot, and wash thoroughly with 5% HCl and distilled water until close to Neutral, repeatedly filtered and washed. Vacu...

Embodiment 1

[0065] 1) Preparation of graphene oxide

[0066] According to the relevant literature, the preparation of graphene oxide was appropriately improved. Mix 5g graphite and 100mL (3:1 volume ratio) H2SO4-HClO4 in an ice bath, stir for 1h to make it fully mixed, place it in the ice bath for 24h, and transfer to Stirring was continued for 24 hours in a warm water bath at 40°C. Heat at 120°C for 4 hours to remove the acid, dilute the reaction solution with distilled water to 800-1000ml, centrifuge, then add an appropriate amount of 0.1mNaOH to mix and stir at 90°C for 2 hours, filter while hot, and wash thoroughly with 5% HCl and distilled water until close to Neutral, repeatedly filtered and washed. Vacuum freeze-drying at -40 °C to obtain graphene oxide samples.

[0067] 2) Synthesis of CTX-coupled graphene

[0068] 150 mg of GO was dispersed in 20 ml of PBS (0.1M, pH=6.0), activated by adding 4 mg of NHS and 6 mg of EDC, and reacted at room temperature. The pH of the mixture w...

Embodiment 2

[0076] Determination of Graphene Oxide Loading Efficiency:

[0077] The obtained graphene oxide and CTX-modified graphene oxide suspension prepared in Example 1 were mixed with adriamycin, and the mass ratio of the two was 1:1. To speed up the loading speed of doxorubicin, heat to 40°C and shake for 8 hours. The content of doxorubicin was detected in each sample, the absorbance was measured at 480nm, and the loading percentage of doxorubicin was calculated. From Figure 5 It can be concluded that the DOX loading per gram of GO-CTX is about 570mg.

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Abstract

A method for preparing a CTX (Chlorotoxin)-targeted oxidized graphene nanometer material comprises the following steps: 1, mixing graphite and H2SO4-HClO4, stirring and mixing the mixture in an ice-bath, continuing stirring in a warm water bath , heating to 100 to 120 DEG C for deacidification, diluting to 800 to 1000 ml and then centrifuging, adding an alkali solution and then mixing and settling, stirring at 70 to 90 DEG C and filtering under the condition of being hot, washing to be approximately neutral, and freeze drying at minus 40 DEG C under the vacuum condition to obtain oxidized graphene; 2, mixing the oxidized graphene with a phosphate buffer solution, adding N-Hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride to perform an activating reaction at room temperature; adjusting the pH value of the mixture to be 7.0 to 8.0, adding CTX for reaction, centrifugating and washing the obtained product, and performing vacuum freeze drying at minus 40 DEG C to obtain the CTX-targeted oxidized graphene nanometer material. The material can be used for transporting an anticancer drug of adriamycin to a brain glioma in a targeted manner.

Description

technical field [0001] The present invention relates to a graphene oxide nanomaterial for anti-tumor drug transport chlorotoxin (CTX) targeting. [0002] The present invention also relates to a preparation method of the above-mentioned graphene oxide nanometer material. [0003] The present invention also relates to the application of the above-mentioned graphene oxide nanomaterials. Background technique [0004] Glioma is a major disease of the human brain and the most common primary tumor of the central nervous system. Because of its invasive growth and the presence of blood-brain barrier (BBB) ​​in the brain, its treatment and early diagnosis have always been important. worldwide problem. [0005] Graphene, is a sp 2 Novel two-dimensional nanomaterials of heterocyclic rings possess many extraordinary electronic, optical, thermal and mechanical properties. Graphene oxide (GO) is an ideal and effective drug nanocarrier obtained by violent oxidation of graphite. Graphen...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/42A61K47/04A61K31/704A61P35/00
Inventor 徐群渊王昊顾微叶玲肖宁
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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