Manganese dioxide-based nano-drug carrier and preparation method and application thereof

A nano-drug carrier, manganese dioxide-based technology, applied in biochemical equipment and methods, drug combinations, pharmaceutical formulations, etc., can solve problems such as poor water solubility, limit large-scale application, and kill cancer cells

Active Publication Date: 2020-10-30
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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  • Manganese dioxide-based nano-drug carrier and preparation method and application thereof
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  • Manganese dioxide-based nano-drug carrier and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Dissolve 20 mg of folic acid in 20 mL of dimethyl sulfoxide and sonicate. Add 40 mg 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC-HCl), 40 mg N-hydroxysuccinimide (NHS) and 100 mg at 37 °C μL of triethylamine (TEA), and stirred in the dark for 20 minutes. Dissolve 100 mg of human serum albumin in 20 mL of deionized water and adjust the pH to 10 with 0.2 M sodium hydroxide solution. The human serum albumin solution was gradually dropped into the FA-NHS solution under stirring, and reacted 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, HSA-FA was obtained after freeze-drying.

[0034] (2) Dissolve 30 mg of HSA-FA in 10 mL of deionized water and add 5 mL of 0.1 M MnCl after ultrasonic dissolution 2 solution. Stir at a constant speed for 20 minutes, then add 1 M sodium hydroxide solution dropwise to the soluti...

Embodiment 2

[0037] (1) Dissolve 40 mg of folic acid in 20 mL of dimethyl sulfoxide and dissolve by ultrasonication. Add 80 mg 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC-HCl), 80 mg N-hydroxysuccinimide (NHS) and 200 mg at 37 °C μL of triethylamine (TEA), and stirred in the dark for 20 minutes. Dissolve 100 mg of human serum albumin in 20 mL of deionized water, and adjust the pH to 10 with 0.2M sodium hydroxide solution. The human serum albumin solution was gradually dropped into the FA-NHS solution under stirring, and reacted 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, HSA-FA was obtained after freeze-drying.

[0038] (2) Dissolve 50 mg of HSA-FA in 10 mL of deionized water and add 5 mL of MnCl with a concentration of 1 M after ultrasonic dissolution 2 solution. Stir at a constant speed for 20 minutes, then add 1 M sod...

Embodiment 3

[0041] (1) Dissolve 40 mg of folic acid in 20 mL of dimethyl sulfoxide and dissolve by ultrasonication. Add 80 mg 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC-HCl), 80 mg N-hydroxysuccinimide (NHS) and 200 mg at 37 °C μL of triethylamine (TEA), and stirred in the dark for 20 minutes. Dissolve 100 mg of human serum albumin in 20 mL of deionized water and adjust the pH to 10 with 0.2M sodium hydroxide solution. The human serum albumin solution was gradually dropped into the FA-NHS solution under stirring, and reacted 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, HSA-FA was obtained after freeze-drying.

[0042] (2) Dissolve 50 mg of HSA-FA in 10 mL of deionized water and add 5 mL of MnCl with a concentration of 1 M after ultrasonic dissolution 2 solution. Stir at a constant speed for 20 minutes, then add 2 M sodi...

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Abstract

The invention relates to a manganese dioxide-based nano-drug carrier, and innovatively combines hunger therapy and gas therapy for cancer treatment. Specifically, folic acid targeting molecules are introduced into human serum protein firstly by utilizing an amidation reaction, and then a nano manganese dioxide carrier is cultured in the protein by utilizing a biomineralization method. Glucose oxidase and L-arginine are loaded at the same time through physical adsorption. The preparation method has the advantages that 1, the targeted drug delivery efficiency and dispersity of the nano manganesedioxide are greatly improved, 2, specific chemical reaction in cancer cells is utilized to consume endogenous glucose and release nitric oxide gas to kill the cancer cells through hunger and gas therapy, 3, the synthesized carrier substance is degradable, and the loaded enzyme and amino acid are endogenous substances of a human body and have no toxic or side effect on the human body, and 4, the anticancer effect is remarkable, and cancer cells can be killed under extremely low biological enzyme concentration.

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 its preparation method and application. 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" due to the inability to obtain a stable nutrient supply. The treatment is clean, non-toxic, and highly effective, so it has received a lot of attention (see: M. Wang, D.M. Wang, Q. Chen, et al., Small 2019 1903895.). However, starvation therapy also faces some problems and challenges: (1) Since 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 , while there is much hypoxi...

Claims

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Application Information

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