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Tumor vessel-tumor cell membrane-cell nucleus continuous targeted drug delivery system, as well as preparation method and application thereof

A technology for tumor blood vessels and cell membranes, which is applied in the field of medical targeted drug delivery system and its preparation, can solve the problems of large individual differences in passive targeting effects and unstable effects, achieve enhanced cancer cell death, and simple and easy synthesis process , the effect of promoting endocytosis

Inactive Publication Date: 2014-12-03
SHANGHAI INST OF CERAMIC CHEM & TECH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Therefore, the passive targeting effect of the EPR effect alone has large individual differences, and the effect is unstable.

Method used

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  • Tumor vessel-tumor cell membrane-cell nucleus continuous targeted drug delivery system, as well as preparation method and application thereof
  • Tumor vessel-tumor cell membrane-cell nucleus continuous targeted drug delivery system, as well as preparation method and application thereof
  • Tumor vessel-tumor cell membrane-cell nucleus continuous targeted drug delivery system, as well as preparation method and application thereof

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preparation example Construction

[0045] The present invention also provides a preparation method for the above-mentioned tumor blood vessel-tumor cell membrane-nucleus continuous targeting drug delivery system. figure 1 A schematic diagram showing the synthesis of the continuous targeted drug delivery system of the present invention, figure 2 A flow chart of the preparation of the continuous targeted drug delivery system of the present invention is shown. Such as figure 1 , 2 As shown, the preparation method of the present invention mainly includes: surface amination of mesoporous silica nanoparticles, grafting of nuclear targeting ligands, and grafting of blood vessel / cell membrane targeting ligands. Among them, when grafting the nuclear targeting ligand, the grafting of the PEG chain can be carried out at the same time, so as to save steps and simplify the process. However, it should be understood that the grafting of the nuclear targeting ligand can also be carried out first, and then the grafting of t...

Embodiment 1

[0079] Synthesis of Mesoporous SiO with Small Particle Size MCM-41 2 Nanoparticles (MSNs): 2 g cetyltrimethylammonium chloride (CTAC) was dissolved in 20 g deionized water. After the solution became clear, 0.8 g of triethanolamine (TEB) was added and vigorously stirred at 95°C. After the solution became clear, 1.5 mL of tetraethyl orthosilicate (TEOS) was added dropwise and stirred continuously for 1 h. After the product was cooled to room temperature, absolute ethanol was added to make the product flocculate, and the product was collected by centrifugation and washed 3 times with absolute ethanol;

[0080] Use ethanol solution of hydrochloric acid to extract the surfactant in the mesoporous channel: weigh 100 mg of mesoporous SiO without removing the surfactant 2 Nanoparticles (MSNs) were ultrasonically dispersed in ethanol solution of hydrochloric acid (10%), and refluxed at 78°C for 6h. Finally, the product was collected by centrifugation and washed thoroughly with absol...

Embodiment 2

[0082] Amino modification on the surface of MSNs: Weigh 50 mg of MSNs in Example 1, ultrasonically disperse them in 100 mL of absolute ethanol, stir vigorously at a constant temperature of 78°C, then add 50 μL of 3-aminopropyltriethoxysilane (APTES), reflux for 4 hours and then centrifuge , washed with absolute ethanol, and finally collected by centrifugation to obtain amino-modified MSNs.

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Abstract

The invention relates to a tumor vessel-tumor cell membrane-cell nucleus continuous targeted drug delivery system, as well as a preparation method and application thereof. The tumor vessel-tumor cell membrane-cell nucleus continuous targeted drug delivery system comprises mesoporous silica nano-particles, RGD polypeptide which is linked to the surfaces of the mesoporous silica nano-particles in a covalent manner and serves as a tumor vessel / tumor cell membrane targeting ligand, and a nuclear localization signal polypeptide sequence serving as a cell nucleus targeting ligand. Under the condition of intravenous injection, the drug-loaded system can be enriched in a tumor tissue by means of the targeting effect of the tumor vessel to reduce the uptake of normal tissues and reduce toxic and side effect, is capable of increasing the phagocytosis amount of tumor cells by means of the identification effect on the tumor cell membrane, and can be used for directly delivering anti-cancer drugs into a cell nucleus by means of the delivery performance of the cell nucleus to increase the concentration of effective drugs, so that an optimal treatment effect can be achieved.

Description

technical field [0001] The invention belongs to the technical field of medical nano-biological materials, and relates to a medical targeted drug delivery system with good biocompatibility, high specific surface area, uniform pore size, drug loading and efficient tumor-specific targeted therapy and its Preparation methods and applications. Background technique [0002] Traditional drugs for treating tumors generally have disadvantages such as poor selectivity to tumors and high toxicity and side effects. How to design a good drug delivery system has become a research hotspot in recent years. Mesoporous silica nanoparticles (MSNs) are considered to be very promising drug delivery vehicles due to their excellent drug delivery and controlled release properties. A large number of studies have shown that the drug delivery system based on MSNs can effectively improve drug utilization, reduce toxic side effects on normal cells, and have significant anticancer properties at the cell...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K9/51A61K47/04A61K47/42A61K47/46A61K41/00A61P35/00A61K31/704A61K33/24A61K31/4745
Inventor 潘黎敏施剑林
Owner SHANGHAI INST OF CERAMIC CHEM & TECH CHINESE ACAD OF SCI
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