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Radiotherapy sensitizer and preparation method thereof

A technology of sensitizer and solvent, which is applied in the field of tumor treatment drugs, and achieves the effects of simple preparation, easy popularization and use, and good application prospects

Active Publication Date: 2021-06-01
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the prior art still lacks a solution to further improve the therapeutic effect of tumor radiotherapy

Method used

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  • Radiotherapy sensitizer and preparation method thereof
  • Radiotherapy sensitizer and preparation method thereof
  • Radiotherapy sensitizer and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0084] Example 1. DNA of tumor cells damaged by radiotherapy slowly accumulates into the cytoplasm.

[0085] Except for a small amount of DNA in the mitochondria, there is no DNA in the cytoplasm of the cell under normal circumstances. Cells undergoing radiotherapy will undergo DNA damage, and the damaged DNA may leak into the cytoplasm. The DNA leaked into the cytoplasm can be stained with double-stranded DNA staining reagent PicoGreen for observation and quantitative analysis. The experimental method is as follows:

[0086] B16F10 tumor cells were seeded in cell culture dishes at a density of 10,000 cells / mL. After 24 hours, they received radiotherapy at a dose of 8Gy, and the B16F10 tumor cells that did not receive radiotherapy were used as the control group. Cells at designated time points after radiotherapy were stained with PicoGreen, and then the accumulation of extranuclear DNA in radiotherapy and non-radiation tumor cells was observed and statistically analyzed by la...

Embodiment 2

[0089] Example 2. Tumor cells stimulated by manganese ions combined with radiotherapy to secrete type I interferon from immune cells

[0090] The pathway of tumor cells expressing type I interferon is blocked in most cases, so the ability of tumor cells to secrete type I interferon after receiving radiotherapy is very weak. Co-incubating immune cells with tumor cells can detect type I interference of immune cells prime expression. BMDCs and Raw264.7 immune cells were selected to co-incubate with radiotherapy B16F10 and CT26 cells respectively, and the concentration of type I interferon in the culture supernatant was detected. The specific experimental method is as follows:

[0091] B16F10 cells were seeded in six-well plates at a density of 50,000 / mL. 24 hours later, he received radiotherapy at a dose of 8Gy. BMDCs were added to a six-well plate at 200,000 per well to incubate with B16F10 cells, a medium containing manganese ions was added so that the final concentration of ...

Embodiment 3

[0093] Example 3. Inhibition of CT26 tumors in vivo by manganese ions combined with radiotherapy

[0094] Construction of CT26 mouse model: BALB / c female mice (6-8 weeks old) used in the experiment were purchased from the Comparative Medicine Center of Yangzhou University and raised according to the requirements of IACUC-NJU. There are 5-6 mice per cage, free to drink and eat, and control 12h light and 12h dark to maintain the healthy growth of mice.

[0095] The method for making the CT26 tumor-bearing mouse model is as follows: the hair on the left and right sides of the mouse abdomen was removed, and 0.1 mL of 3×10 6 The suspension of CT26 tumor cells per mL was injected subcutaneously into the right abdomen of mice, and 0.1 mL of 1×10 6 A suspension of CT26 tumor cells per mL was injected subcutaneously into the left abdomen of the mouse, and the tumor on the right side grew to about 100mm 3 They were randomly divided into 4 groups: normal saline (Saline), Mn ion group (...

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Abstract

The invention provides a radiotherapy sensitizer and a preparation method thereof. The radiotherapy sensitizer comprises one or both of divalent manganese or a source capable of forming divalent manganese. The radiotherapy sensitizer can be combined with radiotherapy to improve the tumor inhibition effect. And when the bivalent manganese loaded on the carrier is selected as the component of the radiotherapy sensitizer, Mn < 2 + > can be slowly released in vivo for 120 hours. The preparation method is simple, basically non-toxic under reasonable dosage, low in raw material cost, easy to obtain and easy to popularize and use, and has a good application prospect.

Description

technical field [0001] The invention belongs to the field of drugs for treating tumors, and in particular relates to a manganese composition as a radiotherapy sensitizer and a preparation method thereof. Background technique [0002] The therapeutic effect of radiotherapy on tumors has been attributed to its ability to induce tumor cell DNA damage or fragmentation, which may lead to direct tumor cell death. However, as early as 1953, Mole et al. found that radiotherapy of local tumors could cause tumor regression in distant metastases that did not receive radiotherapy. The phenomenon is named the far-end effect. When radiotherapy-induced distant effects were discovered, high expectations were placed on the anti-tumor immune response induced by radiotherapy. However, the body's immune tolerance to tumors makes the probability of such distant effects very low. [0003] Current evidence shows that, in addition to directly relying on damaged DNA to induce tumor cell death, ra...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/32A61K9/06A61K47/36A61K47/42A61P35/00
CPCA61K33/32A61K9/06A61K47/36A61K47/42A61P35/00
Inventor 吴锦慧汪超赵宸萱胡一桥
Owner NANJING UNIV
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