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Iron-blocking magnetic nano-drug responding to tumor microenvironment, preparation method and application

A tumor microenvironment, magnetic nanotechnology, applied in antitumor drugs, drug combinations, drug delivery, etc., can solve the problems of difficult to achieve clinical integration of diagnosis and treatment, no mediation of tumor treatment, limited targeting efficiency, etc. Achieve the effect of avoiding premature release, improving performance, and increasing load capacity

Active Publication Date: 2021-09-07
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Silica nanoparticles are widely used in biomedicine and other fields due to their adjustable particle size, stable function and good biocompatibility, and the severe side effects caused by their delivery of chemotherapy drugs are mainly due to the limited targeting efficiency and low treatment selectivity
However, most MRI contrast agents do not have the ability to mediate tumor therapy, making it difficult to achieve clinical integration of diagnosis and treatment.

Method used

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  • Iron-blocking magnetic nano-drug responding to tumor microenvironment, preparation method and application
  • Iron-blocking magnetic nano-drug responding to tumor microenvironment, preparation method and application
  • Iron-blocking magnetic nano-drug responding to tumor microenvironment, preparation method and application

Examples

Experimental program
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Effect test

Embodiment 1

[0029] Example 1 Preparation of iron-blocking magnetic nanomedicine responsive to tumor microenvironment

[0030] In the first step, cetyltrimethylammonium chloride solution (20g) and triethanolamine solution (3.5g) were mixed and stirred at 80°C for 15 minutes, then tetraethyl orthosilicate (1mL) was added dropwise to react 1 hours, then added a mixture of tetraethyl orthosilicate (0.5mL) and bis[3-(triethoxysilyl)propyl]tetrasulfide (1mL) to continue the reaction for 3 hours, centrifuged and washed 3 times, and washed with The extraction was repeated with 1% NaCl in methanol to remove the templating agent. Then transferred to a 95°C water bath, etched in hot water for 3 hours with the assistance of ammonia water to corrode the inner core of the nanoparticles, washed 3 times and then freeze-dried.

[0031]In the second step, take ferrous acetylacetonate (400mg), thioether hybrid hollow mesoporous silica nanoparticles (25mg), and urea (10mg) and dissolve them completely in 30...

Embodiment 2

[0037] Example 2 Preparation of iron-blocking magnetic nanomedicine responsive to tumor microenvironment

[0038] In the first step, cetyltrimethylammonium chloride solution (20g) and triethanolamine solution (3.5g) were mixed and stirred at 80°C for 15 minutes, then tetraethyl orthosilicate (1mL) was added dropwise to react 1 hours, then added a mixture of tetraethyl orthosilicate (0.5mL) and bis[3-(triethoxysilyl)propyl]tetrasulfide (1mL) to continue the reaction for 3 hours, centrifuged and washed 3 times, and washed with The extraction was repeated with 1% NaCl in methanol to remove the templating agent. Then transferred to a 95°C water bath, etched in hot water for 3 hours with the assistance of ammonia water to corrode the inner core of the nanoparticles, washed 3 times and then freeze-dried.

[0039] In the second step, ferrous acetylacetonate (200 mg), thioether hybrid hollow mesoporous silica nanoparticles (25 mg), and urea (10 mg) are completely dissolved in 30 ml o...

Embodiment 3

[0045] Example 3 Preparation of iron-blocking magnetic nanomedicine responsive to tumor microenvironment

[0046] In the first step, cetyltrimethylammonium chloride solution (20g) and triethanolamine solution (3.5g) were mixed and stirred at 80°C for 15 minutes, then tetraethyl orthosilicate (1mL) was added dropwise to react 1 hours, then added a mixture of tetraethyl orthosilicate (0.5mL) and bis[3-(triethoxysilyl)propyl]tetrasulfide (1mL) to continue the reaction for 3 hours, centrifuged and washed 3 times, and washed with The extraction was repeated with 1% NaCl in methanol to remove the templating agent. Then transferred to a 95°C water bath, etched in hot water for 3 hours with the assistance of ammonia water to corrode the inner core of the nanoparticles, washed 3 times and then freeze-dried.

[0047] In the second step, ferrous acetylacetonate (40mg), thioether hybrid hollow mesoporous silica nanoparticles (25mg), and urea (10mg) were completely dissolved in 30ml of et...

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Abstract

The invention provides an iron-blocking magnetic nano-drug responding to a tumor microenvironment, a preparation method and application. The preparation method comprises the following steps: firstly, constructing thioether-hybridized mesoporous silica nanoparticles with a core / shell structure based on a chemical homology principle, so as to improve the biodegradability of the mesoporous silica nanoparticles; secondly, corroding an internal core by adopting an ammonia water etching method to obtain hollow mesoporous silica nanoparticles, so as to improve the loading capacity of a chemotherapeutic drug; and introducing an iron precursor into a nanoparticle skeleton through a dissolution-growth strategy, so that the iron precursor has magnetic resonance imaging capacity. Transferrin grafted by polyethylene glycol can be specifically combined with a transferrin receptor highly expressed on the surface of hepatocellular carcinoma, so that tumor targeted delivery and high accumulation of the drug are realized, the drug can be disintegrated under the action of rich glutathione in the tumor microenvironment, and rapid release of the drug is triggered, and as a result, the killing effect of the drug on tumors is remarkably improved, the toxic and side effects of the drug are reduced, and the tolerance of the drug is improved.

Description

technical field [0001] The invention belongs to the preparation of nano-medicines, in particular to transferrin-modified iron-blocked magnetic mesoporous silicon dioxide nano-medicines, a preparation method and an application in the treatment and diagnosis of hepatocellular carcinoma. Background technique [0002] Hepatocellular carcinoma (referred to as liver cancer) ranks fourth among cancer-related causes of death worldwide (ranking second among men), and its incidence rate is rising steadily. Most patients with significant clinical symptoms have entered the middle and late stages, and the median survival time is usually less than two years. The treatment methods for liver cancer mainly include surgical resection, interventional therapy, systemic intravenous chemotherapy, radiotherapy, and immunotherapy. At present, chemotherapy is still one of the first-line treatment strategies for advanced liver cancer, and doxorubicin is the most commonly used chemotherapy drug in the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/64A61K47/60A61K31/704A61K33/26A61K49/08A61K49/18A61P1/16A61P35/00C01B33/18
CPCA61K47/6949A61K47/6923A61K47/644A61K47/60A61K31/704A61K33/26A61K49/08A61K49/186A61K49/1866A61P1/16A61P35/00C01B33/18A61K2300/00
Inventor 余日胜周巧妹杜永忠卢园飞周佳萍王晓洁杨晓艳余洁倪
Owner ZHEJIANG UNIV
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