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Application of tungsten-based polyoxometalate compound to preparation of radiodynamic tumor treatment medicines

A polymetallic oxygen cluster, tumor treatment technology, applied in the field of medicine, can solve the problems of limited enhancement effect, no large-scale clinical application, etc., and achieve the effect of increasing water solubility and biocompatibility

Pending Publication Date: 2021-12-10
上海市质子重离子临床技术研发中心
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the past, it was believed that radiotherapy sensitizing drugs fit the T1PE mechanism of drugs directly producing ROS under X-rays, and every increase of 1wt% (gold / water) would have a radiotherapy enhancement effect of 1.4 times. This enhancement effect is very limited, so there is no significant effect. clinical application at scale

Method used

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  • Application of tungsten-based polyoxometalate compound to preparation of radiodynamic tumor treatment medicines
  • Application of tungsten-based polyoxometalate compound to preparation of radiodynamic tumor treatment medicines
  • Application of tungsten-based polyoxometalate compound to preparation of radiodynamic tumor treatment medicines

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] A tungsten-based polymetallic oxygen cluster compound:

[0029] Na 24 Cs[CsGd 6 As 6 W 63 o 218 (H 2 O) 14 (OH) 4 ]·3CsCl·nH 2 O(Gd-1);

[0030] Its synthetic verification:

[0031] 1. Weigh 100mg of Gd-1 solid for thermogravimetric analysis test.

[0032] 2. Take 1mL of 1mg / mL Gd-1 aqueous solution, add twice the volume of aqua regia to digest at 50°C for 1 day, evaporate the solution to dryness and re-constant to 10mL with 1M dilute nitric acid, and the obtained liquid is used for ICP-OES elemental analysis test .

[0033] 3. Prepare 1mg / mL Gd-1 aqueous solution, pass through a 220nm microporous membrane for high-resolution transmission electron microscope testing.

[0034] like figure 2 As shown, the Gd-1 solid lost 6.63% of its mass when the temperature rose to 270 °C, representing the amount of crystallization water in the crystal. It can be calculated that there are about 71 crystal waters in a Gd-1 molecular cluster.

[0035] The results of ICP-OE...

Embodiment 2

[0038] Verification of ROS generation ability of tungsten-based multi-metal oxide compound Gd-1:

[0039]1. Prepare 0.15mg / mL Gd-1 acetate buffer solution (pH=5.2) in three parts (named A, C, D); prepare another acetate buffer solution that does not contain Gd-1 ( B), adding hydrogen peroxide with a final concentration of 100 μM to solutions B, C and D, respectively, and then adding 3,3' with a final concentration of 0.2 mg / mL to solutions A, B, C and D, respectively, 5,5'-Tetramethylbenzidine (TMB), hydrogen peroxide is used to simulate the high concentration of hydrogen peroxide in the tumor microenvironment, TMB is used to capture the hydroxyl radicals generated in the solution, which is shown as ultraviolet absorption (peak at 642nm ) enhancement;

[0040] 2. Expose the B and D solutions configured in step 1 to X-rays (4Gy, the irradiation time is about 75s); A and C solutions are placed in the dark for the same time, and then immediately test the absorbance values ​​of a...

Embodiment 3

[0043] Verification of the killing ability of tungsten-based polymetallic oxygen cluster compound Gd-1 on tumor cells:

[0044] 1. Prepare 1.5 mg / mL Gd-1 aqueous solution, and use DMEM medium to gradiently dilute to 15, 30, 75, 150, 300 μg / mL.

[0045] 2. 4T1.2 cells in 5×10 per well 3 The concentration of cells was seeded in two 96-well cell culture plates, and cultured in 100 μL of DMEM medium for 24 h. Then the cell culture medium was replaced with the medium prepared in step 1 and incubated for 24 hours. After incubation, cells were washed three times with PBS to remove medium and unincorporated material. One of the culture plates was irradiated with X-rays (4Gy) while the other was not treated. The cells were cultured again for 24 hours and stained with CCK-8. Then, the microplate reader was used to detect and calculate the cell viability.

[0046] 3. 4T1.2 cells in 5×10 per well 2 The concentration of cells was seeded in a 6-well cell culture plate and cultured for 2...

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Abstract

The invention discloses an application of a tungsten-based polyoxometalate compound to preparation of radiodynamic tumor treatment medicines, and aims to solve the major problems that the energy utilization efficiency of existing radiotherapy is low, and the structure and the function of existing radiodynamic medicines are not perfect. The research and development of a water-soluble radiodynamic medicine with high X-ray absorption and high ROS generation capability is extremely urgent. Therefore, the water-soluble radiodynamic medicine based on the tungsten-based polyoxometalate compound is provided, is used for enhancing the curative effect of radiotherapy, can be well dissolved in water so as to be dispersed to the whole focus and enhance the X-ray absorption of the focus, and enhances the energy deposition around the medicine through a T2PE mechanism so as to cause a higher radiodynamic curative effect.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to the application of a tungsten-based polymetallic oxygen cluster compound in the preparation of radiodynamic tumor therapy drugs. Background technique [0002] On a global scale, radiation therapy has provided great help to human beings against malignant tumors. Among the many high-energy particle rays, the traditional X-ray is still the most used at present. As a source of ionizing radiation, X-rays have been widely used in clinical treatment to improve the survival rate of patients due to their deep penetration and high radiation energy. [0003] However, due to the weak absorption and scattering of X-rays by human lesions, most of the X-ray energy passes out of the body or is absorbed by normal tissues. At present, the mainstream way to improve the utilization rate of X-rays is to use radiosensitizing drugs with high Z media. For example, the use of nano-medicine...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61P35/00B82Y5/00B82Y15/00B82Y40/00C01D17/00C01G41/00
CPCA61K41/0038A61P35/00B82Y5/00B82Y15/00B82Y40/00C01G41/006C01D17/00Y02A50/30
Inventor 孙筠邓勇
Owner 上海市质子重离子临床技术研发中心
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