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NK (Natural Killer) cell sensitizer prepared by combining functionalized nano-selenium with metformin and application of NK cell sensitizer

A technology of NK cells and metformin, applied in the field of pharmaceutical compounds, can solve the problems of non-expression, unclear mechanism, killing tumor cells, etc., and achieve the effect of simple operation, reduced survival rate, and high-efficiency inhibitory effect

Pending Publication Date: 2022-03-15
GUANGDONG JINAN ESTABLISHED SELENIUM SOURCE NANO TECH RES INST CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] NK-92 cells are a kind of immune cells similar to NK cell activity. They have the main characteristics of NK cells and the main expression receptors. TNF-α, etc., and then kill tumor cells; and NK-92 cells can efficiently recognize and kill tumor cells without affecting the survival of normal cells. This special mechanism is not clear, but it is speculated that NK-92 cells do not express Immunoglobulin-like receptors (KIRs) on NK cells

Method used

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  • NK (Natural Killer) cell sensitizer prepared by combining functionalized nano-selenium with metformin and application of NK cell sensitizer
  • NK (Natural Killer) cell sensitizer prepared by combining functionalized nano-selenium with metformin and application of NK cell sensitizer
  • NK (Natural Killer) cell sensitizer prepared by combining functionalized nano-selenium with metformin and application of NK cell sensitizer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Example 1 Functionalized SeNPs combined with metformin enhances the immunotherapy effect of NK-92 cells.

[0063] 1. Culture of HepG2 cells and NK-92 cells: HepG2 cells and NK-92 cells were purchased from the American Standard Culture Collection (ATCC), HepG2 was cultured with complete medium (DMEM, Gibco), and NK-92 cells were cultured with minimum essential medium (MEM, Gibco) culture, and add 10% (v / v) fetal bovine serum (FBS, Gibco) and 1% (v / v) double antibody (penicillin and streptomycin mixed solution, Gibco), cultured at 37°C in a humidified incubator with 5% (v / v) carbon dioxide.

[0064] 2. Study the survival rate of human liver cancer cells HepG2 with different modified nano-selenium and metformin. In order to test whether functionalized SeNPs combined with metformin can enhance the killing effect of NK-92 cells on tumor cells. First, we tested the toxicity evaluation of functionalized SeNPs and metformin on liver cancer HepG-2 cells. Such as Picture 1-1 ...

Embodiment 2

[0069] Embodiment 2, different forms of selenium (Na 2 SeO 3 , TW80-SeNPs and SeC) combined with metformin and NK-92 cells to study the anti-hepatic tumor activity in vitro.

[0070] After HepG2 cells were cultured (20000 / mL) for 24 hours, NK cells, metformin and nano-selenium were not added as the blank control, and NK cells (5 times the number of HepG2 cells were added) and metformin at a final concentration of 5 mM were added to the experimental group. Combined with 2.5 μM of different forms of selenium (Na 2 SeO 3 , TW80-SeNPs and SeC), metformin at a final concentration of 5 mM combined with 2.5 μM of different forms of selenium (Na 2 SeO 3 , TW80-SeNPs and SeC) were treated with HepG2 cells for 24 hours, and then NK-92 cells were added to treat HepG2 cells for 24 hours. The result is as Figure 4 As shown, it can be seen from the figure that after the cells were treated with NK-92 alone, the cell survival rate dropped to 90%. When the cells were treated with diffe...

Embodiment 3

[0071] Example 3, TW80-SeNPs combined with metformin enhanced the anti-tumor activity of patient-derived NK cells. Drug combination can enhance the immunotherapy effect of NK-92 cells. Then, whether the combination of drugs can enhance the therapeutic effect of NK cells from patients. Therefore, we tested the immunotherapeutic effect of TW80-SeNPs combined with metformin on NK cells from patients in 6 cases. Such as Figure 5 From the experimental results shown in A, it can be seen that in 6 NK patients, TW80-SeNPs combined with metformin enhanced the immunotherapy effect of NK cells in patients by 0.8-10 times, and there were some differences in the enhancement times for different living NK cells. Among them, the enhancement factor of case 1 was between 0.8 and 1.9 times; the enhancement factor of case 2 was between 1.1 and 1.5 times; the enhancement factor of case 3 was between 0.8 and 5.2 times; the enhancement factor of case 4 was between 2.8 and 4.6 times The enhanceme...

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Abstract

The invention discloses an NK (Natural Killer) cell sensitizer prepared by combining functionalized nano-selenium with metformin and application of the NK cell sensitizer. Functional nano-selenium and metformin are combined to serve as an NK cell sensitizer to assist NK cells for application. The functionalized nano-selenium is at least one of independent nano-selenium, nano-selenium modified by polyacrylamide hydrochloride, nano-selenium modified by polyvinylpyrrolidone, nano-selenium modified by Tween 80, nano-selenium modified by polysaccharide, tumor targeting nano-selenium modified by folic acid and tumor targeting nano-selenium modified by transferrin; the NK cell is an NK-92 cell. The NK cell sensitizer can stimulate NK cells to secrete more cell factors so as to improve the anti-tumor effect of cell therapy, the raw materials of the obtained nano-selenium sensitizer are cheap and easy to obtain, the operability of synthesis and purification steps is high, the synthesis scale is properly expanded, and commercialization and application of drugs are achieved.

Description

technical field [0001] The invention belongs to the technical field of medical compounds, and in particular relates to an NK cell sensitizer prepared by functionalized nano-selenium combined with metformin and its application in anti-tumor. Background technique [0002] Liver cancer is the sixth most common cancer in the world, accounting for 11% of cancer mortality. Diabetes is a metabolic disease characterized by dysregulation of blood sugar and insulin. Many studies have found that the longer the onset duration of diabetes, the greater the risk of liver cancer, which is 2 to 3 times higher than that of non-diabetic patients. The possible carcinogenic mechanisms are the patient's own hyperglycemia, chronic inflammation, obesity and hyperinsulinemia. Hyperglycemia can cause oxidative stress through glycosylation of hemoglobin to release ferrous ions (as a pro-oxidant), generating free radicals; autologous chronic inflammation induces tumor necrosis factor (TNF-α) and inte...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/04A61K47/59A61K47/58A61K47/61A61K47/64A61K35/17A61P35/00A61P37/04A61K31/155
CPCA61K33/04A61K31/155A61P35/00A61P37/04A61K47/58A61K47/59A61K47/61A61K47/644A61K35/17A61K2300/00
Inventor 李晓玲陈填烽刘婷陈义康李海伟
Owner GUANGDONG JINAN ESTABLISHED SELENIUM SOURCE NANO TECH RES INST CO LTD
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