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A kind of manganese dioxide-based nano drug carrier and its preparation method and application

A nano-drug carrier, manganese dioxide-based technology, applied in biochemical equipment and methods, drug combinations, pharmaceutical formulations, etc., can solve the problems of restricting large-scale application, killing cancer cells, poor water solubility, etc., and achieves remarkable targeting effect , easy to operate, targeted and stable effect

Active Publication Date: 2022-07-05
QUFU NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, some properties of manganese dioxide itself limit its large-scale application in drug delivery: (1) Manganese dioxide has poor water solubility, and nanoscale size regulation can improve its water solubility to a certain extent, but it cannot avoid long-term (2) Most of the current targeted modification work on manganese dioxide is cumbersome and inefficient, so a simple and efficient targeted modification process is needed (see L.T. Meng, S.J. Gan, Y. Zhou, et al. al., Bio. Sci. 72019 168-177; Q.Q. Sun, F. He, H.T. Bi, et al., Chem. Eng. J. 362 2019 679-691.); (3) In addition, the oxidation process of glucose will Generate hydrogen peroxide by-product, L-arginine (L-Arg) can react with hydrogen peroxide to generate nitric oxide, which can further kill cancer cells (see W.P. Fan, N. Lu, P. Huang, et al., Angew . Chem. Int. Edit. 55 2016 1-6.)
Therefore, L-arginine can cooperate with glucose oxidase to fight cancer. However, there is no technology and method for nano manganese dioxide to combine starvation therapy and nitric oxide (NO) gas therapy at the same time.

Method used

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  • A kind of manganese dioxide-based nano drug carrier and its preparation method and application
  • A kind of manganese dioxide-based nano drug carrier and its preparation method and application
  • A kind of manganese dioxide-based nano drug carrier and its preparation method and application

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Experimental program
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Effect test

Embodiment 1

[0033] Dissolve 20 mg of folic acid in 20 mL of dimethyl sulfoxide and dissolve by sonication. Add 40 mg 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC-HCl), 40 mg N-hydroxysuccinimide (NHS) and 100 μL at 37 °C Triethylamine (TEA), and the reaction was stirred for 20 minutes in the dark. Dissolve 100 mg of human serum protein in 20 mL of deionized water and adjust the pH to 10 using 0.2 M sodium hydroxide solution. The human serum protein solution was gradually dropped into the FA-NHS solution under stirring, and the reaction was performed in the dark for 24 hours. The obtained solution was put into a 12000 M dialysis bag, pre-dialyzed in 0.1 M PBS solution, and then transferred to deionized water for dialysis. After dialysis, freeze-drying was completed to obtain HSA-FA.

[0034] (2) 30 mg HSA-FA was dissolved in 10 mL of deionized water, and 5 mL of MnCl with a concentration of 0.1 M was added after ultrasonic dissolving. 2 solution. Stir at a uniform s...

Embodiment 2

[0037] (1) Dissolve 40 mg of folic acid in 20 mL of dimethyl sulfoxide and dissolve by sonication. 80 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC-HCl), 80 mg of N-hydroxysuccinimide (NHS) and 200 mg of N-hydroxysuccinimide (NHS) were added at 37 °C. μL triethylamine (TEA), and the reaction was stirred for 20 minutes in the dark. Dissolve 100 mg of human serum protein in 20 mL of deionized water and adjust the pH to 10 using 0.2 M sodium hydroxide solution. The human serum protein solution was gradually dropped into the FA-NHS solution under stirring, and the reaction was performed in the dark for 24 hours. The obtained solution was put into a 12000 M dialysis bag, pre-dialyzed in 0.1 M PBS solution, and then transferred to deionized water for dialysis. After dialysis, freeze-drying was completed to obtain HSA-FA.

[0038] (2) 50 mg HSA-FA was dissolved in 10 mL of deionized water, and 5 mL of 1 M MnCl was added after ultrasonic dissolving. 2 solut...

Embodiment 3

[0041] (1) Dissolve 40 mg of folic acid in 20 mL of dimethyl sulfoxide and dissolve by sonication. 80 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC-HCl), 80 mg of N-hydroxysuccinimide (NHS) and 200 mg of N-hydroxysuccinimide (NHS) were added at 37 °C. μL triethylamine (TEA), and the reaction was stirred for 20 minutes in the dark. Dissolve 100 mg of human serum protein in 20 mL of deionized water and adjust the pH to 10 using 0.2 M sodium hydroxide solution. The human serum protein solution was gradually dropped into the FA-NHS solution under stirring, and the reaction was performed in the dark for 36 hours. The obtained solution was put into a 12000 M dialysis bag, pre-dialyzed in 0.1 M PBS solution, and then transferred to deionized water for dialysis. After dialysis, freeze-drying was completed to obtain HSA-FA.

[0042] (2) 50 mg HSA-FA was dissolved in 10 mL of deionized water, and 5 mL of 1 M MnCl was added after ultrasonic dissolving. 2 solut...

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Abstract

The invention relates to a manganese dioxide-based nanometer drug carrier, and innovatively combines starvation therapy and gas therapy for cancer treatment. Specifically, the use of amidation reaction was the first to introduce folic acid targeting molecules on human serum protein, and then the nano-manganese dioxide carrier was cultured in the protein by biomineralization method. Glucose oxidase and L-arginine were simultaneously loaded by physical adsorption. The advantages are: 1. The targeted drug delivery efficiency and dispersibility of the nano-manganese dioxide are greatly improved. 2. Use specific chemical reactions in cancer cells to consume endogenous glucose and release nitric oxide gas to kill cancer cells through starvation and gas therapy. 3. The synthetic carrier material is degradable, and the loaded enzymes and amino acids are endogenous substances in the human body, which have no toxic and side effects on the human body. 4. Significant anti-cancer effect, can kill cancer cells at a very small concentration of biological enzymes.

Description

technical field [0001] The invention belongs to the technical field of materials and biomedicine, and in particular relates to a manganese dioxide-based nano drug carrier and a preparation method and application thereof. Background technique [0002] In recent years, "starvation therapy" with glucose oxidase (GOX) as the core has gradually emerged. Glucose oxidase can continuously consume the endogenous glucose of cancer cells, and cancer cells will be "starved to death" because they cannot obtain a stable supply of nutrients. This therapy is clean, non-toxic, and has considerable therapeutic effects, so it has received great attention (see: M. Wang, D.M. Wang, Q. Chen, et al., Small 2019 1903895.). However, starvation therapy also faces some problems and challenges: (1) Because glucose oxidase does not have special selectivity, it needs a specific nano-drug delivery system to assist it into cancer cells; (2) The oxidation process of glucose requires sufficient oxygen , an...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/02A61K47/42A61K47/22A61K9/19A61K38/44A61K31/198A61P35/00
CPCA61K47/02A61K47/42A61K47/22A61K9/19A61K38/443A61K31/198A61P35/00C12Y101/03004A61K2300/00
Inventor 公培伟刘哲彭景一刘明月黄炎李慧翟明珠
Owner QUFU NORMAL UNIV
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