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Bionic nano-carrier with dual functions of oxidation and anti-oxidation, and preparation method and application thereof

A dual-function, biomimetic nanotechnology, applied in the field of biomimetic nanocarriers and their preparation, to achieve the effects of improving utilization, reducing damage, and reducing systemic toxicity

Active Publication Date: 2020-04-14
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] To sum up, how to improve the aggregation degree of drugs in the tumor site and how to release the carrier specifically in the tumor site is the key to reduce the side effects; in addition, the drug resistance of traditional chemotherapy drugs is also an important reason for affecting the therapeutic effect.

Method used

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  • Bionic nano-carrier with dual functions of oxidation and anti-oxidation, and preparation method and application thereof
  • Bionic nano-carrier with dual functions of oxidation and anti-oxidation, and preparation method and application thereof
  • Bionic nano-carrier with dual functions of oxidation and anti-oxidation, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] (1) Preparation of functionalized SOD enzyme (Fe-SOD)

[0054] Dissolve 5 mg of SOD enzyme and 0.2 mg of ammonium ferrous sulfate in 5 mL of deoxygenated deionized water, stir for 30 min under a nitrogen atmosphere, then add 2.5 mL of 50 mmol / L sodium borohydride at a rate of 0.1 mL / min with a micro-injection pump (full nitrogen flow), react for 1.5h, concentrate by ultrafiltration with a 10kDa ultrafiltration tube to a final volume of 2mL, store under nitrogen flow at 4°C, and name it Fe-SOD.

[0055] (2) Preparation and detection of organometallic framework (ZIF-8)

[0056] Dissolve 7.5mL of 5mol / L dimethylimidazole in water, add 1mL of 0.5mol / L zinc nitrate hexahydrate solution under stirring, add pure water to the final volume of 15mL, and react at 10000rpm after 20min Centrifuge for 20 min, and wash three times with deionized water to obtain ZIF-8. The results of ultraviolet absorption spectroscopy showed that there was no residual reagent in the supernatant afte...

Embodiment 2

[0065] Embodiment 2 drug release experiment in vitro

[0066] The β-lap / Fe-SOD@ZIF-8@RBC-F obtained in Example 1 were dissolved in 1 mol / L PBS with pH=7.4 and pH=5.4, respectively. The nanoparticle solution of each group was sealed in a dialysis bag with a molecular weight cut-off of 3500 Da and dialyzed against 10 mL of PBS. At certain intervals, 100 μl aliquots were taken from the solution outside the dialysis bag for HPLC analysis or ICP-MS detection, and the contents of β-lap and Fe were calculated to obtain the drug release curves of β-lap and Fe. The result is as image 3 shown. At pH 7.4, ferrous ions and β-lapachone were barely released, and 18.9% and 9.4% of ferrous ions and β-lapachone had been released within 36h. On the contrary, at pH 7.4, the release rates of ferrous ions and β-lapachone from β-lap / Fe-SOD@ZIF-8@RBC-F reached 72.4% and 78.2%, respectively, within 36 h. These results indicated that the pH-triggered disintegration of β-lap / Fe-SOD@ZIF-8@RBC-F ac...

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Abstract

The invention provides a bionic nano-carrier with dual functions of oxidation and anti-oxidation, and a preparation method and an application thereof. The bionic nano-carrier comprises an erythrocytemembrane and an organic-metal framework coated in the erythrocyte membrane, and the organic-metal framework is loaded with functionalized SOD enzyme and beta-lapaquone. After the bionic nano-carrier reaches the acidic environment of tumor cells, metal-ligand bonds in the MOF are hydrolyzed to generate protonated ligands to destroy the erythrocyte membrane and release the enzyme and drug; the beta-lapafenone is catalyzed by quinone oxidoreductase 1 highly expressed by tumor cells to generate a large number of superoxide anions, and is catalyzed by the SOD enzyme to generate hydrogen peroxide, and iron ions in the SOD enzyme catalyze the hydrogen peroxide through a Fenton reaction to generate hydroxyl radicals in order to kill the tumor cells. The bionic nano-carrier provided by the invention does not generate drug resistance through enzyme treatment, can significantly reduce the systemic toxicity caused by drug application, and has extremely high clinical application prospects.

Description

technical field [0001] The invention relates to the technical field of nanomedicine, in particular to a biomimetic nanocarrier with dual functions of oxidation and anti-oxidation and its preparation method and application. Background technique [0002] Malignant tumors are one of the major diseases that threaten human health and life. According to the World Health Organization, as the number of cancer deaths worldwide continues to increase, 13 million people will die of cancer by 2030. The number of cancer deaths in China is as high as 2.3 million every year, and the cancer mortality rate has ranked first in the urban and rural mortality rates in my country. There are many clinical treatment methods for tumors at present, the most important of which are still surgical resection, radiotherapy and chemotherapy, but there are still many deficiencies in it. Surgical resection is difficult to completely cure the tumor, and it is easy to relapse; chemotherapy has problems of mul...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/24A61K47/46A61K47/02A61K38/44A61K31/352A61P35/00
CPCA61K9/5176A61K9/5123A61K9/5115A61K31/352A61K38/446C12Y115/01001A61P35/00
Inventor 戴箭刘雯阮淼亮薛巍
Owner JINAN UNIVERSITY
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