Preparation method of polysaccharide-based nanometer particles sensitive to tumor microenvironments

A tumor microenvironment and nanoparticle technology, which is applied in the field of environment-sensitive nanoparticle preparation, can solve the problems of tumor cell killing, poor tumor selectivity, tissue damage, etc., and achieve broad application prospects, efficient and convenient synthesis, and uniform particle size Effect

Active Publication Date: 2015-10-14
SHANGHAI JIAO TONG UNIV
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Problems solved by technology

At present, clinical tumor treatment mainly includes three methods: surgical resection, chemical drug therapy and radiotherapy, among which the use of chemical drug therapy is the most common, but the problem it faces is that when chemical drugs are used alone, because the selectivity of chemical drugs to tumors is not strong, In addition to killing tumor cells, it will also cause great damage to normal tissues

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  • Preparation method of polysaccharide-based nanometer particles sensitive to tumor microenvironments

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Embodiment 1

[0029] Dissolve 0.25 g of dextran (molecular weight of 40,000 Da) in 25 ml of water, stir until fully dissolved, pass nitrogen to deoxidize for 1 hour, add dilute nitric acid solution containing 0.06 g of cerium ammonium nitrate under nitrogen protection and uniform stirring, and make the reaction The final pH of the system is between 1-2. After about 5 minutes, 0.06 ml of acrylic acid monomer was added, and half an hour later, 0.012 g of diallyl disulfide crosslinking agent (dissolved in 0.2 ml of dimethyl sulfoxide solution) was added, and the reaction was carried out at 30°C for 5 hours. After the reaction, transfer to a dialysis bag with a molecular weight cut-off of 14,000Da, and dialyze in pure water for one week to ensure the removal of impurities such as unreacted monomers in the reaction system, that is, to obtain dextran-based tumor-reducing environment-sensitive nanoparticles. Aqueous solution of particles. Nanoparticles were obtained after freeze-drying.

[0030]...

Embodiment 2

[0032] Dissolve 0.6 g of temperature-sensitive hydroxypropyl cellulose (molecular weight: 80,000 Da) in 50 ml of water, stir until fully dissolved, and pass argon for 1 hour to remove oxygen in the system, under argon protection and uniform stirring Add 0.04 g of dilute nitric acid solution of ammonium cerium nitrate to make the final pH of the reaction system between 1-2. After about 10 minutes, 0.05 ml of methyl acrylate was added, and after 30 minutes, 0.040 g of bisacrylcystamine cross-linking agent (dissolved in an appropriate amount of aqueous solution) was added, and the reaction was carried out at 30° C. for 4 hours. After the reaction, transfer to a dialysis bag with a molecular weight cut-off of 14,000Da, and dialyze in pure water for a week to ensure the removal of impurities such as unreacted monomers in the reaction system, that is, to obtain a temperature-sensitive hydroxypropyl cellulose-based Tumor-reducing environment-sensitive nanoparticles in aqueous solutio...

Embodiment 3

[0034] Example 3: Dissolve 0.1 g of chitosan (molecular weight: 30,000 Da) in 50 ml of 1% (v / v) acetic acid solution, stir until fully dissolved, pass nitrogen to deoxidize for 1 hour, and add under nitrogen protection and uniform stirring 0.02 g of potassium persulfate in water. After about 5 minutes, add 0.02 g of tert-butyl acrylate, and half an hour later, add 0.003 g of bis(2-methacryloyloxyethyl) disulfide as a crosslinking agent (dissolved in 0.5 ml of dimethyl sulfoxide), React at 65°C for 4 hours. After the reaction, transfer to a dialysis bag with a molecular weight cut-off of 14,000Da, and dialyze in pure water for one week to ensure the removal of impurities such as unreacted monomers in the reaction system, that is, to obtain a stable aqueous solution of nanoparticles based on chitosan. Nanoparticles were obtained after freeze-drying.

[0035] The nanoparticles obtained in this system are regular in shape by transmission electron microscopy, basically spherical,...

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Abstract

The invention discloses a preparation method of polysaccharide-based nanometer particles sensitive to tumor microenvironments. The preparation method comprises the steps: preparing an initiator solution by adding an initiator to a water-soluble polysaccharide solution and adjusting pH, then adding a monomer-containing solvent (or directly adding monomers) and a cross-linking agent sensitive to reducing environments for carrying out polymerization and cross-linking reaction so as to obtain nanometer particles, and finally carrying out dialysis or centrifugal treatment and freeze drying to obtain the polysaccharide-based nanometer particles sensitive to tumor microenvironments. The preparation method is green, pollution-free, high in yield, efficient and convenient in synthesis and low in cost; the prepared polysaccharide-based nanometer particles are high in solid content and uniform in particle sizes; due to introduction of the cross-linking agent sensitive to reducing environments, the nanometer particles sensitive to tumor microenvironments can be prepared and have a wide application prospect in aspects of design and application of carriers for tumor treatment.

Description

technical field [0001] The invention relates to a tumor microenvironment-sensitive polymer nanoparticle and a preparation method thereof, belonging to the field of environment-sensitive nanoparticle preparation. Background technique [0002] Tumors seriously endanger human health, and tumor treatment is a difficult problem that modern medicine must overcome. At present, clinical tumor treatment mainly includes three methods: surgical resection, chemical drug therapy and radiotherapy, among which the use of chemical drug therapy is the most common, but the problem it faces is that when chemical drugs are used alone, because the selectivity of chemical drugs to tumors is not strong, In addition to killing tumor cells, it will also cause great damage to normal tissues. Therefore, choosing an appropriate drug carrier to release the drug specifically at the tumor site and effectively reduce systemic toxicity is a breakthrough in current chemotherapy. [0003] The tissue at the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08F251/00C08F251/02A61K47/36
Inventor 窦红静王灏周淑彦孙康
Owner SHANGHAI JIAO TONG UNIV
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