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Application of pH-responsive copper-based compound nanomaterial serving as disulfiram carrier in preparation of multi-level selective tumor treatment medicine

A technology of nanomaterials and copper compounds, applied in the field of nanobiomedicine, can solve the problems of low selectivity tumor toxicity and side effects

Pending Publication Date: 2021-05-14
ZHEJIANG UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the systemic delivery of chemotherapeutic drugs has its limitations, such as severe side effects caused by high dose administration and low selective tumor toxicity

Method used

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  • Application of pH-responsive copper-based compound nanomaterial serving as disulfiram carrier in preparation of multi-level selective tumor treatment medicine
  • Application of pH-responsive copper-based compound nanomaterial serving as disulfiram carrier in preparation of multi-level selective tumor treatment medicine
  • Application of pH-responsive copper-based compound nanomaterial serving as disulfiram carrier in preparation of multi-level selective tumor treatment medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] 1. Preparation of copper-doped mesoporous silica nanoparticles

[0047] Copper chloride (0.034g) was first dissolved in a small amount of ethanol (1mL) and tetraethylorthosilicate (1mL), and ultrasonically mixed evenly. The solution was then slowly added dropwise to distilled water (50 mL) in which cetyltrimethylammonium bromide (0.18 g) and ammonium fluoride (0.3 g) were dissolved. After magnetic stirring for 4 h, the synthesized nanospheres were collected by centrifugation (8000 rpm, 10 min) and washed three times with distilled water and ethanol. The product was vacuum freeze-dried for 12 hours and sintered at 600° C. in air for 6 hours to obtain copper-doped mesoporous silica nanospheres. figure 1 It is the TEM image of Cu-MSNs, and the results show that the particle size distribution of the Cu-MSNs is uniform, and it is a spherical mesoporous structure, about 100nm; figure 2 is the EDS elemental distribution of Si, O, and Cu in Cu-MSNs, indicating that copper is...

Embodiment 2

[0050] Example 2, copper ion release of copper-doped mesoporous silica nanospheres at different pH:

[0051] Make 1mL copper ion concentration 2mg·mL -1 The Cu-MSNs solution was sealed in a dialysis bag (MCWO: 1000 Da), and immersed in centrifuge tubes filled with 20 mL buffer media of different pH (pH=7.4, 6.5 and 5.4). Shake the centrifuge tube at a speed of 200 rpm, and within a given interval, remove 1 mL of buffer solution and return 1 mL of fresh buffer solution, and analyze the copper ion concentration in the removed 1 mL buffer solution by ICP-AES. Figure 4 The copper ion release curves of Cu-MSNs under different acidic conditions show that Cu-MSNs exhibit a pH-dependent copper ion release ability. Under the acidic environment of pH 5.4, 25% can be released from Cu-MSNs within 12 hours. Cu 2+ , and only a very small amount (5%) of Cu in a neutral solution at pH 7.4 2+ let go.

Embodiment 3

[0052] Example 3. Drug release of copper-doped mesoporous silica nanospheres loaded with disulfiram at different pHs:

[0053] The 5mL mass concentration is 1.0mg·mL -1 The Cu-MSNs / DSF were placed in a dialysis bag (MW = 3500) and immersed in 100 mL of buffer medium, which was PBS with different pH (pH = 7.4, 6.5 and 5.4) containing 10% ethanol. At given time intervals, 2 mL of buffer was withdrawn and 2 mL of fresh buffer was returned, and the released DSF was determined by UV-vis absorption technique. Figure 5 The DSF release curves of Cu-MSNs / DSF under different acidic conditions show that the DSF release is still less than 20% after 24 hours of reaction in the simulated physiological environment, i.e. pH 7.4, while in the simulated tumor acid environment, i.e. pH 5. After 24 hours of reaction under the conditions of 4, the release of DSF far exceeded 60%. Image 6 It is the UV-Vis spectrum of Cu-MSNs and DSF under different acidic conditions. It can be seen that under t...

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Abstract

The invention provides application of a pH-responsive copper-based compound nanomaterial serving as a disulfiram carrier in preparation of a multi-level selective tumor treatment medicine. According to the invention, a functional carrier for performing copper doping (Cu-MSNs) in mesoporous silicon dioxide nanoparticles is prepared by adopting a metal ion doping template method, and a nanodrug delivery system is obtained after disulfiram is loaded. The nanodrug delivery system prepared by the invention can release copper ions and disulfiram after being enriched at a tumor site through an EPR effect, plays a role in both a tissue level and a cell level, improves the effect of chemotherapeutic drugs, reduces systemic toxic and side effects caused by a traditional drug delivery route, and provides a new research direction for in-situ local treatment of tumors.

Description

technical field [0001] The invention belongs to the field of nano-biomedicine, and relates to the application of a pH-responsive copper-based compound nanomaterial as a disulfiram carrier in the preparation of multi-level selective therapeutic drugs for tumors. Background technique [0002] Malignant tumor is a disease that seriously threatens human health. Although significant progress has been made in the diagnosis and treatment of cancer, how to effectively control and overcome malignant tumors has become an urgent problem to be solved. In recent years, chemotherapy using various drugs followed by surgery or radiation therapy is one of the most commonly used cancer treatment strategies in clinical practice. However, the systemic delivery of chemotherapeutic drugs has its limitations, such as severe side effects caused by high dose administration and low selective tumor toxicity. With the development of nanotechnology, nanoparticles with tumor microenvironment responsiven...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K31/145A61K9/00A61K33/34A61P35/00B82Y5/00B82Y30/00B82Y40/00
CPCA61K31/145A61K33/34A61K47/6923A61K9/0019A61P35/00B82Y5/00B82Y30/00B82Y40/00A61K2300/00
Inventor 余靓徐庆赵帆车声雷李涓应耀李旺昌郑精武乔梁蔡伟
Owner ZHEJIANG UNIV OF TECH
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