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Preparation method of CPZ-coupled MS2 protein nanoparticles and application thereof in breast cancer resistance

A technology of nanoparticles, zinc phthalocyanine, applied in the preparation of anti-breast cancer drugs, in the field of preparation of monocarboxyzinc phthalocyanine nanoparticles, can solve the problems of poor water solubility, toxic and side effects, short half-life in vivo, etc. The effect of uniform diameter, reducing drug side effects and simple process

Active Publication Date: 2020-02-28
FUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The photosensitizer zinc phthalocyanine can kill tumor cells with micromolar efficacy, but due to the disadvantages of zinc phthalocyanine itself, such as poor water solubility, short half-life in vivo, toxic side effects on normal tissue cells, and low accumulation in tumor tissues, to a certain extent, Limiting the clinical application of zinc phthalocyanine

Method used

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  • Preparation method of CPZ-coupled MS2 protein nanoparticles and application thereof in breast cancer resistance
  • Preparation method of CPZ-coupled MS2 protein nanoparticles and application thereof in breast cancer resistance
  • Preparation method of CPZ-coupled MS2 protein nanoparticles and application thereof in breast cancer resistance

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] A method for preparing MS2 protein nanoparticles, comprising the steps of:

[0032] (1) Express MS2 protein in Escherichia coli, centrifuge the crushed bacteria at high speed to remove the precipitate, put the supernatant in a water bath at 37 ℃ for 8 hours, and digest the residual RNA in the supernatant with the nuclease of the bacterial cells themselves And DNA, virus-like particles are resistant to RNase, so the RNA wrapped by the coat protein is not digested;

[0033] (2) Add solid NaCl to a final concentration of 1 mol / L, and ice-bath for 1 hour. Centrifuge at 4°C and 12000 r / min for 10 minutes to remove bacterial debris, and transfer the supernatant to another clean centrifuge tube;

[0034] (3) Add solid polyethylene glycol PEG6000 to a final concentration of 10% (W / V), shake at 37°C for 30 minutes, and place in an ice bath overnight to precipitate the virus-like particles;

[0035] (4) Centrifuge at 4°C and 12000 rpm for 10 minutes to recover the precipitated vi...

Embodiment 2

[0040] A preparation method of MS2-CPZ nanoparticles, comprising the steps of:

[0041] (1) Dissolve zinc monocarboxyphthalocyanine in dimethyl sulfoxide at a concentration of 55 μmol / L, add dicyclohexylcarbodiimide with a final concentration of 100 μmol / L for activation, and activate at room temperature for 48 hours;

[0042] (2) Add MS2 protein nanoparticles dissolved in phosphate solution to the activated zinc phthalocyanine solution in step (1), and react at room temperature for 48 hours to obtain crude MS2-CPZ nanoparticles, the reaction concentration of zinc phthalocyanine and MS2 The ratio is: 33:1, the volume ratio of organic phase and aqueous phase is 1:5;

[0043] (3) Centrifuge the crude product in step (2) to remove the precipitate. The condition for centrifuging to remove the precipitate is to centrifuge at 8000 rpm for 10 min, dialyze the remaining supernatant into the phosphate solution, and then centrifuge to remove the precipitate to obtain the supernatant;

...

Embodiment 3

[0046] Embodiment 3: MS2-CPZ nano particle size distribution

[0047] The particle size of MS2 protein nanoparticles in Example 1 was carried out at room temperature at 25°C, and the parallel measurement was performed three times. The average particle size of MS2 protein nanoparticles was about 28.99 d.nm, and the dispersion coefficient was about 0.0299. The results are shown in image 3 A; The average particle size of pure MS2-CPZ nanoparticles is about 29.21 d.nm, and the dispersion coefficient is about 0.037. The results are shown in image 3 B, Compared with MS2 protein nanoparticles, the average particle size of MS2-CPZ nanoparticles in Example 1 is increased by about 0.2 nm, and the dispersion coefficient PDI is less than 0.1, showing good monodispersity. The electron microscopy results of the prepared MS2-CPZ nanoparticles are shown in image 3 c.

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Abstract

The invention discloses a preparation method of CPZ-coupled MS2 protein nanoparticles and an application thereof in breast cancer resistance. The CPZ is coupled on the surface of MS2 protein nanoparticles by covalent coupling, so that the MS2 protein nanoparticles have the characteristics of good water solubility, high drug loading rate, uniformity and stability. Hydrophobicity of phthalocyanine compounds leads to aggregation of the compounds in physiological environment, which affects photophysical (reduced 1O2 formation), chemical (reduced solubility) and biological (insufficient tumor localization) properties of the compounds and reduces the photodynamic therapy (PDT) efficacy of the compounds. Through the nano covalent coupling, the drug effect of ZnPc on breast cancer is improved, nanoparticles can obviously improve the solubility of monocarboxylic groups, provide appropriate particle size and surface properties, and prolong blood circulation, thereby allowing selective accumulation of tumors through enhanced permeability and retention effect (EPR), so that the nanoparticles have a good effect in the application of breast cancer.

Description

technical field [0001] The invention relates to monocarboxy phthalocyanine zinc, in particular to the preparation of water-soluble monocarboxy phthalocyanine zinc nanoparticles and its application in the preparation of anti-breast cancer drugs. Background technique [0002] Breast cancer is one of the most common malignant tumors in women. With the rapid development of economy and society, the incidence of breast cancer is increasing year by year in developing countries. In recent years, its incidence has shown a significant upward trend. Breast cancer is a highly heterogeneous malignant tumor with various types, and the treatment and prognosis of different types of breast cancer are significantly different. Triple-negative breast cancer accounts for about 15 percent of breast cancers and is more common in younger women. Triple-negative breast cancer is defined as the absence of three receptors, estrogen receptor, progesterone receptor, and human epidermal growth factor re...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/64A61K47/69A61K41/00A61P35/00
CPCA61K41/0071A61K47/64A61K47/6929A61P35/00
Inventor 黄明东郭楠楠李林林袁彩江龙光
Owner FUZHOU UNIV
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