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Preparation and application of tumor-targeting drug based on unsaturated fatty acid nanoparticles

A nanoparticle, carboxyl technology, applied in the field of nanomedicine

Active Publication Date: 2019-10-11
SOUTH CHINA NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the combined treatment of lipid peroxidation, chemotherapy and photodynamic therapy based on unsaturated fatty acids has not been reported.

Method used

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  • Preparation and application of tumor-targeting drug based on unsaturated fatty acid nanoparticles
  • Preparation and application of tumor-targeting drug based on unsaturated fatty acid nanoparticles
  • Preparation and application of tumor-targeting drug based on unsaturated fatty acid nanoparticles

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0123] The synthesis of embodiment 1 nanoparticle DPSPAH / MPPa / DOX

[0124] 1. Preparation of mPEG-DHA chain.

[0125] Utilize EDC / NHS to activate the carboxyl group of unsaturated fatty acid (DHA) in solvent DMF, and then react with amino polyethylene glycol (mPEG-NH 2 ) condensation reaction of amino groups to form mPEG-DHA chains.

[0126] Specific method: Dissolve 100 μmol (19.17 mg) ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) in 1 mL dimethylformamide (DMF), 100 μmol (11.509 mg) hydroxyl Thiosuccinimide (NHS) was dissolved in 1 mL of dimethylformamide (DMF), 20 μmol (6.57 mg) of docosahexaenoic acid (DHA) was first dissolved in 1 mL of dimethyl sulfoxide, and then added 3mL of DMF, then mix the DHA solution and the EDC / NHS solution, stir at room temperature for 4h, then add 40μmol (80mg) mPEG-NH, a hydrophilic substance containing amino groups 2 , stirred at room temperature for 24h. Finally, it was dialyzed in PBS (pH7.4), and then freeze-dried with...

Embodiment 2

[0137] Example 2 Micellar mPEG-DHA, Micellar DSPE-PEG-Anti-HER 2 and characterization of nanoparticles

[0138] 1. Infrared spectrum detection

[0139] 1. Experimental method

[0140] In the infrared detection process, we mainly detect the formation of amide bonds. Specific detection method: Make the prepared micellar mPEG-DHA into a solid with a vacuum freeze dryer, take about 3 mg, and take about 3 mg of amino PEG and DHA respectively. The sample must be dried in a 40°C oven before infrared detection. Dry the dried sample and KBr in a dryer, mix 1-2 mg of the sample to be tested with 200 mg of pure KBr and grind them evenly, and grind the mixture to a particle size of less than 2 μm to avoid the influence of scattered light. The mixture is placed in a mold, and the mixture is pressed into a transparent sheet with a pressure of 5-10 MPa on a hydraulic press, and measured on the machine.

[0141] 2. Experimental results

[0142] The result is as figure 2 Shown, the car...

Embodiment 3

[0188] Example 3 Nanoparticles inhibit breast cancer in vitro

[0189] 1. Morphological observation

[0190] 1. Experimental method

[0191] Take out the cultured cells from the incubator, digest with trypsin for 2min, add 4mL culture medium and blow the cells. Add 3mL of cell suspension to a centrifuge tube, add 1mL of culture medium, and blow the cells to make the cells evenly suspended. Use a pipette gun to draw 100 μL of the cell suspension and add it to a 24-well plate to allow the cells to adhere to the wall and culture for 6 hours. Take out the synthesized nano drug-loaded micelles under light-shielded conditions, shake slightly and shake well. Take out the cultured cells, suck off the cell waste liquid, add PBS to wash twice, and add fresh medium. Then add the nanoparticles DPSPAH / MPPa / DOX prepared in Example 1, incubate in the dark for 4h, and irradiate laser light (660nm, 100mW / cm 2 , 10min). After culturing in the incubator for 0h, 6h, 12h and 24h, photographs...

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Abstract

The invention discloses preparation and application of a tumor-targeting drug based on unsaturated fatty acid nanoparticles. Carboxyl groups of docosahexaenoic acid and amino groups of amino polyethylene glycol are subjected to a condensation reaction to prepare a micelle mPEG-DHA; carboxyl groups of DSPE-PEG-COOH and amino groups of Anti-HER2 are subjected to a condensation reaction to prepare amicelle DSPE-PEG-Anti-HER2; the micelle mPEG-DHA, the micelle DSPE-PEG-Anti-HER2, pyropheophorbide-a methyl ester and adriamycin are subjected to self-assembly to obtain the targeting nanoparticles DPSPAH / MPPa / DOX used for lipid peroxidation and photodynamic-chemotherapy combined tumor therapy. The nanoparticles DPSPAH / MPPa / DOX have a particle size of about 190 nanometers and good stability, can effectively control the release of chemotherapeutic drugs, have good biocompatibility, high efficiency, low toxicity and higher application prospects in the fields of nano drug carriers and nano drug tumor treatment.

Description

technical field [0001] The invention relates to the technical field of nano-medicines, and more specifically, to the preparation and application of a tumor-targeting drug based on unsaturated fatty acid nanoparticles. Background technique [0002] Breast cancer is one of the most common malignant tumors in women all over the world, and its incidence ranks first among female malignant tumors. In recent years, its incidence has been on the rise, and it is the second leading cause of death in malignant tumors after lung cancer, and the age of onset tends to be younger, which seriously threatens the lives and health of patients. [0003] At present, surgery is the main treatment for breast cancer, and it is supplemented by radiotherapy, chemotherapy, endocrine therapy and photodynamic therapy. Although the current treatment methods are relatively complete, most breast cancers still face the problems of easy recurrence, cancer cell proliferation and metastasis, and it is difficu...

Claims

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Application Information

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IPC IPC(8): A61K9/107A61K47/60A61K47/68A61K31/202A61K31/704A61K41/00A61P35/00
CPCA61K9/1075A61K31/202A61K31/704A61K41/0057A61K47/60A61K47/6803A61P35/00A61K2300/00
Inventor 吴宝艳薛永永关燕清
Owner SOUTH CHINA NORMAL UNIVERSITY
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