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Liver-cancer-targeted doxorubicin-supporting silica-gold composite material, and preparation method and application thereof

A technology of loading doxorubicin and silicon dioxide, which is applied in the nano-biomedicine field of biomedical materials science, can solve the problems of centralized heating in untreated areas, poor therapeutic effect, and large toxic and side effects, so as to reduce toxic and side effects, Low immunogenicity and high biocompatibility

Inactive Publication Date: 2014-08-20
EAST CHINA NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The disadvantage of these methods in the prior art is that the liver is located in a relatively deep part of the body, and the above adding method can only heat the superficial part of the body, and cannot centrally heat the treatment area, and it is easy to cause damage to the normal tissues around the liver cancer
Therefore, there is an urgent need for a new type of material that can heat the liver cancer tissue, effectively disperse and quickly release chemotherapy drugs inside the liver cancer, so as to solve the shortcomings of existing nano-drug carriers and hyperthermia methods, which have large toxic side effects and poor therapeutic effects.

Method used

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  • Liver-cancer-targeted doxorubicin-supporting silica-gold composite material, and preparation method and application thereof
  • Liver-cancer-targeted doxorubicin-supporting silica-gold composite material, and preparation method and application thereof
  • Liver-cancer-targeted doxorubicin-supporting silica-gold composite material, and preparation method and application thereof

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Experimental program
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Effect test

Embodiment 1

[0062] Embodiment 1: Preparation of nano-silica-gold core-shell particles

[0063] Synthesis of seeded core nanoparticles on the surface of silica nanomaterials by first using 3-aminopropyltriethoxysilane to ammonia the surface of silica nanoparticles, followed by reduction of synthesized gold nanoparticles using tetrakishydroxymethylphosphonium chloride , and finally the chloroauric acid solution is reduced by formaldehyde, a large number of gold nanocrystals are generated in the solution, and then these crystals grow with the gold nanoparticles on the seed core as nucleation sites, and finally form a complete core-shell structure of nano-silica- Gold core-shell particles. For the specific process of synthesizing silica-gold nano-core-shell particles in this example, refer to Chinese patent document 200710040691.8 "A nanocomposite silica-metal core-shell particle and its preparation".

Embodiment 2

[0064] Embodiment 2: polyethylene glycol diamine (NH 2 -PEG-NH 2 )Synthesis

[0065] PEG→NPC-PEG-NPC

[0066] PEG2000 (10.0g, 10mmol) and freshly distilled pyridine (3.955g, 50mmol) were added to 70mL of dry dichloromethane (DCM) solution, under nitrogen protection, the p-NPC (8.07 g, 40mmol) was added dropwise to the reaction system, after the dropwise addition was completed, the reaction solution was raised to normal temperature and continued to react for 24 hours. After the reaction, the p-NPC-activated PEG2000 was reprecipitated with pre-cooled glacial ether, and dried in vacuum before use.

Embodiment 3

[0067] Embodiment 3: Synthesis of Cys-PEG-Dox

[0068] Cystamine hydrochloride (Cys, 0.612g, 2.72mmol) and TEA (0.568g, 5.61mmol) were dissolved in 5mL of DMF, and PEG-NPC (2.787g, 0.540mmol) in DMF was The solution (10 mL) was added dropwise into the flask and reacted overnight. The reaction solution was reprecipitated twice with pre-cooled ice ether and dried in vacuo to obtain the crude Cys-PEG-NPC product. Then Cys-PEG-NPC (0.2g, 0.08mmol) was dissolved in 10mL DMSO, then 50mg of doxorubicin hydrochloride (0.08mmol) and 57 μL TEA were added, and the reaction was carried out under nitrogen protection at room temperature for 48 hours. After the reaction, the reaction liquid Add 30 mL of aqueous solution to the solution, and then use a dialysis bag with a molecular weight cut-off of 1000 to dialyze for 3 days to remove unreacted cystamine and Dox. After dialysis, freeze-dry to obtain purple Cys-PEG-Dox dry powder. The absorption peak intensity of Cys-PEG-Dox at 488nm was de...

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Abstract

The invention discloses a liver-cancer-targeted doxorubicin-supporting silica-gold composite material, and a preparation method and application thereof. The composite material comprises silica-gold nanometer core-shell particles, a targeting adhesion peptide and doxorubicin; doxorubicin is subjected to chemical modification for forming A SH-PEG-Dox prodrug, and the prodrug is linked to silica-gold nanometer core-shell particles via Au-S bonds; and the targeting adhesion peptide is linked to the silica-gold nanometer core-shell particles via Au-S bonds. The material is good in biological compatibility, has specific optical properties and good targeting property, the material can enable the supported medicine to be transferred to liver cancer cells and rapidly releases the medicine, and the material has the cooperative treatment effects of chemotherapy and thermotherapy.

Description

technical field [0001] The invention belongs to the technical field of nano-biomedicine of biomedical material science, and relates to a silicon dioxide-gold nanocomposite material loaded with doxorubicin targeting liver cancer and its preparation method and application. Background technique [0002] Cancer is one of the leading causes of death in the world. According to the report of the World Health Organization (WHO), since 2000, the annual incidence of cancer has reached 10 million, and the number of deaths has reached 7.4 million, accounting for about 13% of all deaths. Among them, lung cancer , stomach, colon, liver and breast cancers are responsible for the majority of cancer deaths each year. Traditional chemotherapy has achieved remarkable results in the clinical treatment of tumors, but these anticancer drugs have certain toxic and side effects, such as: liver and kidney toxicity, hair loss, cardiotoxicity, nausea, loss of appetite, etc. Doxorubicin is one of thes...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K47/48A61K31/704A61K47/42A61K47/04A61K47/02A61P35/00
Inventor 刘顺英梁重时谢叶归
Owner EAST CHINA NORMAL UNIV
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