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Application of carbon nanomaterial SWCNT and derivative thereof in inhibition of tumor stem cells and preparation of drugs for treating tumors

A technology of tumor stem cells and derivatives, applied in the direction of anti-tumor drugs, drug combinations, carbon active ingredients, etc., to achieve the effect of improving sensitivity, high biocompatibility, and inhibiting tumor growth

Active Publication Date: 2017-06-06
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there are no other reports at home and abroad that SWCNT and its derivatives can specifically target and inhibit CSC and TGFβ1 signaling pathways

Method used

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  • Application of carbon nanomaterial SWCNT and derivative thereof in inhibition of tumor stem cells and preparation of drugs for treating tumors
  • Application of carbon nanomaterial SWCNT and derivative thereof in inhibition of tumor stem cells and preparation of drugs for treating tumors
  • Application of carbon nanomaterial SWCNT and derivative thereof in inhibition of tumor stem cells and preparation of drugs for treating tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Dissolve 5-10 mg of SWCNT-Raw, SWCNT-COOH and MWCNT in ultra-pure water, ultrasonically disperse them with a probe-type ultrasonic instrument, and then add hydrochloric acid with a final concentration of 1-6M. After continuing to ultrasonically disperse in the ultrasonic cleaner, the nanomaterial precipitate in the solution is separated by centrifugation, and then the precipitate is washed with ultrapure water several times, and finally resuspended with a small amount of ultrapure water, and dispersed in the ultrasonic cleaner by ultrasonic method. In water, nanomaterials stably suspended in water are finally obtained, and the concentration is about 100-150 μg / mL.

[0054] Osteosarcoma cells MNNG / HOS were cultured in serum-free medium. When the cells were in the logarithmic growth phase, 5-10 μg / mL SWCNT-Raw, SWCNT-COOH and MWCNT were added to incubate for 24 hours, and the cells were collected and placed in In 2% glutaraldehyde overnight. Subsequently, the cells were ...

Embodiment 2

[0056] According to existing research reports, common osteosarcoma cells can dedifferentiate under the action of TGFβ1 to form CSC. We take osteosarcoma cell MNNG / HOS as an example to illustrate the inhibitory effect of SWCNT and its derivatives on osteosarcoma cell dedifferentiation and CSC formation. MNNG / HOS was cultured in serum-free medium containing 4ng / mL LTGFβ1, and different concentrations of SWCNT-Raw, SWCNT-COOH and MWCNT were added for treatment. Such as Figure 4 As shown in A, after 5 days, SWCNT-Raw and SWCNT-COOH could significantly inhibit the formation of balloon-like CSCs, and this inhibitory effect was enhanced with the increase of the concentration of SWCNT nanomaterials. However, MWCNT as a control material failed to show the inhibitory effect on the dedifferentiation of osteosarcoma cells and the formation of CSC. Such as Figure 4 As shown in B, compared with the control group (Control), SWCNT-COOH can significantly inhibit the expression of osteosar...

Embodiment 3

[0059] The MNNG / HOS cells were cultured in the pH 6.4 serum-free medium containing TGFβ1 to simulate the acidic microenvironment in the tumor; the MNNG / HOS cells were cultured in the pH 7.4 serum-free medium containing TGFβ1 while culturing in 3% O 2 In the hypoxic incubator, the hypoxic microenvironment in the tumor was simulated; SWCNT-Raw and SWCNT-COOH were added to the medium for treatment, and the same volume of ultrapure water was added to the control group (Control). After 3 or 5 days, if Figure 5 As shown, compared with the control group (Control), SWCNT and its derivatives can significantly inhibit the dedifferentiation of MNNG / HOS cells to form spherical CSCs under both acidic and hypoxic conditions. This shows that the inhibitory effect of SWCNT on the dedifferentiation of tumor cells and the formation of tumor stem cells is not limited to normal conditions, but also applicable to the extreme microenvironment of acidity and hypoxia in tumors.

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Abstract

The invention discloses application of a carbon nanomaterial SWCNT and a derivative thereof in inhibition of cancer stem cells (CSC) and preparation of drugs for treating cancers. The application of the carbon nanomaterial SWCNT and the derivative thereof in inhibition of the cancer stem cells and preparation of the drugs for treating the cancers comprises the purposes: 1) the SWCNT and the derivative thereof can obviously inhibit the formation of the CSC; 2) the SWCNT and the derivative thereof can obviously enhance the sensitivity of cancer cells in a cancer microenvironment to chemotherapy drugs and promote the killing forces of the chemotherapy drugs; 3) the SWCNT and the derivative thereof can obviously reduce the number of the CSC in a cancer tissue and cancer blood vessel density, can obviously weaken the proliferation capacity of the cancer cell and so on and can inhibit the growth of the cancer; and 4) the SWCNT and the derivative thereof can obviously inhibit related gene expressions of a TGF(beta) signaling pathway and the downstream of the TGF(beta) signaling pathway so as to destroy the cancer microenvironment on which the CSC depends for existence. The application of the carbon nanomaterial SWCNT and the derivative thereof in inhibition of the cancer stem cells and preparation of the drugs for treating the cancers, disclosed by the invention, has the advantages that the material preparation method is simple, low in cost and easy to operate; the obtained aqueous SWCNT and the derivative thereof are specifically targeted at the cancer microenvironment, inhibit the CSC cell populations and realize wide application prospect in the treatment of the cancers.

Description

technical field [0001] The present invention relates to an inorganic nanomaterial used for tumor treatment, in particular to a kind of SWCNT and its derivatives in destroying tumor microenvironment, inhibiting TGFβ signaling pathway, inhibiting tumor stem cells, reducing tumor blood vessel density and tumor cell proliferation ability, increasing tumor cell Sensitivity to chemotherapeutic drugs and application in tumor therapy. Background technique [0002] Cancer stem cells (CSCs) are a group of tumor cells with stem cell-like characteristics in tumor tissues, which play a vital role in the occurrence, development and malignant metastasis of tumors. CSC is highly resistant to chemotherapeutic drugs and can avoid the killing of chemotherapeutic drugs. At present, chemotherapy, a routine clinical tumor treatment method, can only remove ordinary tumor cells, but cannot effectively kill CSCs in tumors, which is the key reason for tumor recurrence and treatment failure. Therefo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/44A61P35/00
CPCA61K33/44
Inventor 松阳洲苗彦彦
Owner SUN YAT SEN UNIV
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