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Anti-tumor controlled release nanocomposite and preparation method thereof

A nano-composite, anti-tumor drug technology, applied in the field of anti-tumor controlled-release nano-composite, can solve the problems of unfavorable biological application, poor water solubility, etc.

Inactive Publication Date: 2011-04-13
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the compound is generally easily soluble in organic solvents and has poor water solubility, which is not conducive to biological applications.

Method used

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  • Anti-tumor controlled release nanocomposite and preparation method thereof
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  • Anti-tumor controlled release nanocomposite and preparation method thereof

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preparation example Construction

[0043] The main steps of the preparation of the nano-composites for the controlled release of anti-tumor drugs provided by the present invention are as follows: the nano-diamonds are subjected to strong acid carboxylation treatment, and ultrasonically dispersed in 50% DMSO / H 2 O, add doxorubicin (also paclitaxel or methotrexate, etc.) connected with the enzyme self-degrading chain, and stir magnetically at room temperature. The obtained complex was dispersed in triple-distilled water, the membrane-penetrating peptide TAT was added, magnetically stirred at room temperature, and dried to obtain a doxorubicin controlled-release nanocomplex (TAT-ND-Phe-Lys-PABC-DOX).

[0044] In the method for preparing the above-mentioned doxorubicin controlled-release nanocomposite of the present invention, the treatment process of nano-diamonds through strong acid carboxylation is: adding nano-diamonds to H 2 SO 4 -HClO 4 (3:1) strong acid mixed solution, stirred at 40°C for 24h, refluxed in ...

Embodiment 1

[0052] 1) Preparation of carboxylated nanodiamonds:

[0053] Add 0.5 g nanodiamonds to 20 mL H 2 SO 4 -HClO 4 (3:1) in the mixed solution, stirred at 40°C for 24h, centrifuged, refluxed in 0.1M NaOH aqueous solution at 90°C for 2h, centrifuged, then refluxed in 0.1M HCl aqueous solution at 90°C for 2h, centrifuged, washed with three distilled water several times, Vacuum dry.

[0054] 2) Preparation of ND-Phe-Lys-PABC-DOX nanocomposite:

[0055] Add 4 mg of carboxylated nanodiamonds to 50% dimethyl sulfoxide aqueous solution, and disperse them by ultrasonication at room temperature for 4 h. Add 0.4 mg of Phe-Lys-PABC-DOX to the dispersed nano-diamond solution, stir magnetically at room temperature for 24 hours to completely bind Phe-Lys-PABC-DOX to the nano-diamond, centrifuge, discard the supernatant, and wash with three-distilled water.

[0056] 3) Preparation of TAT-ND-Phe-Lys-PABC-DOX nanocomposite:

[0057] After ultrasonically dispersing the ND-Phe-Lys-PABC-DOX nano...

Embodiment 2

[0065] Study on the adsorption isotherm of nanodiamonds and Phe-Lys-PABC-DOX:

[0066] Add 1 mg of nanodiamonds to the centrifuge tubes respectively, and add Phe-Lys-PABC-DOX with a mass concentration of 0.08, 0.11, 0.14, 0.17, 0.20, and 0.23 mg / mL to the centrifuge tubes in sequence. Turn, shake for 28 hours, centrifuge, take the supernatant in a cuvette, measure the ultraviolet absorption of Phe-Lys-PABC-DOX at 492nm, calculate the supernatant amount according to its standard curve, and further calculate the adsorption amount. According to the formula

[0067] Langmuir isotherm equation: To Ce vs. Do linear equation: y=1.3323x+0.3279, R 2 = 0.3666. According to the formula Freundlich isotherm equation in LogC e to Logq e Do the linear equation: y=0.8654x+0.2243R 2 = 0.9112.

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Abstract

The invention discloses an anti-tumor controlled release nanocomposite and a preparation method thereof. The nanocomposite utilizes nano diamonds after carboxylation treatment as carriers, and comprises adsorption enzyme self degradation chains and cell-penetrating peptides. The preparation method is implemented as follows: dispersing nano diamonds after carboxylation treatment of a strong acid in a dimethyl sulfoxide aqueous solution, adding an anti-tumor drug connected with a self degradation chain, and stirring under room temperature to obtain a composite; and dispersing the obtained composite in water, adding the cell-penetrating peptides, and stirring and drying at room temperature to obtain the anti-tumor controlled release nanocomposite. The nano carrier composite in the invention is simple and convenient in preparation, has no toxicity and pollution, and is easy for industrialization. In vitro research shows that the composite can realize controlled release of an anti-tumor drug, enhance the killing effect of the drug on tumors, and provide a new material and method for drug transport.

Description

technical field [0001] The invention relates to an anti-tumor controlled-release nanocomposite. [0002] The present invention also relates to a preparation method of the above-mentioned anti-tumor controlled-release nanocomposite. Background technique [0003] Doxorubicin (DOX) is a periodic non-specific antitumor antibiotic with strong anticancer activity and broad antitumor spectrum. However, its clinical application is limited due to its toxic and side effects. [0004] Phenylalanine (Phe)-lysine (Lys) is the specific substrate of cathepsin B. Cathepsin B can be overexpressed in tumors. When this substrate is linked to doxorubicin, drug release occurs primarily at the tumor site. However, because the substrate chain is too short, when it is connected with a larger volume of doxorubicin, the action of the enzyme on the substrate will be weakened due to steric hindrance. A self-degrading chain (PABOH) is introduced between the substrate and doxorubicin, which will red...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K31/337A61K31/519A61K31/704A61P35/00A61K47/64
Inventor 叶玲黄珊珊戚颖哲邵建群王迎
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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