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A biomimetic nano-carrier with dual functions of oxidation and anti-oxidation, its preparation method and application

A dual-function, biomimetic nanotechnology, applied in the field of biomimetic nanocarriers and its preparation, to achieve the effects of avoiding multidrug resistance, reducing damage, and high clinical application prospects

Active Publication Date: 2022-01-18
JINAN UNIVERSITY
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  • 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 toxic and 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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  • A biomimetic nano-carrier with dual functions of oxidation and anti-oxidation, its preparation method and application
  • A biomimetic nano-carrier with dual functions of oxidation and anti-oxidation, its preparation method and application
  • A biomimetic nano-carrier with dual functions of oxidation and anti-oxidation, its preparation method and application

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, and then add 2.5 mL of 50 mmol / L boron at a rate of 0.1 ml / min using a microsyringe pump Sodium hydride (full nitrogen flow), react for 1.5h, concentrate by ultrafiltration with a 10 kDa ultrafiltration tube, to a final volume of 2 mL, store under nitrogen flow at 4°C, and name it Fe-SOD.

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

[0056] Dissolve 7.5 mL of 5 mol / L dimethylimidazole in water, add 1 mL of 0.5 mol / L zinc nitrate hexahydrate solution under stirring, add pure water to make the final volume 15 mL, and react for 20 min Centrifuge at 10,000 rpm for 20 min and wash with deionized water three times to obtain ZIF-8. The results of ultraviolet absorption spectroscopy showed that there was no residual reagent in the su...

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 for 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 36 hours. In contrast, at pH 5.4, 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 a...

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Abstract

The invention provides a biomimetic nano-carrier with dual functions of oxidation and anti-oxidation, a preparation method and application thereof. The biomimetic nano-carrier provided by the invention comprises red blood cell membrane and an organometallic framework coated in the red blood cell membrane, and the organometallic framework is loaded with functionalized SOD enzyme and β-lapachone. After the biomimetic nanocarrier reaches the acidic environment of tumor cells, the metal-ligand bond in the MOF is hydrolyzed to produce protonated ligands that destroy the red blood cell membrane, and the enzyme and drug are released; β-lapachone is oxidized and reduced by the quinone highly expressed in tumor cells Enzyme 1 catalyzes the production of a large amount of superoxide anion, which is catalyzed by SOD enzyme to produce hydrogen peroxide. Finally, iron ions in SOD enzyme catalyze hydrogen peroxide to produce hydroxyl free radicals through Fenton reaction, thereby killing tumor cells. The biomimetic nano-carrier provided by the invention not only does not produce drug resistance through enzyme treatment, but also can significantly reduce systemic toxicity caused by drug administration, and has a very high clinical application prospect.

Description

technical field [0001] The invention relates to the technical field of nano-medicine, in particular to a bionic nano-carrier 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. 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 them. Surgical resection is difficult to completely cure the tumor, and it is easy to relapse; chemotherapy has problems of multidrug resistance and high toxicity; radiation and high toxic side effects of radiotherapy cause a lot of pain to patients. Finding high-efficiency and low-toxicity tumor treatment strategies has always been a research hotspot. Chemotherapy is an important means of clinical cancer treatment, but due to the high toxicity and poor...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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