CN106798752A - Carbon nanomaterial SWCNT and its derivative are used to suppress the application in tumor stem cell and preparation tumor - Google Patents
Carbon nanomaterial SWCNT and its derivative are used to suppress the application in tumor stem cell and preparation tumor Download PDFInfo
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Abstract
A kind of application in being used to suppress tumor stem cell (CSC) and preparation tumor the invention discloses carbon nanomaterial SWCNT and its derivative, including：1) SWCNT and its derivative can significantly inhibit the formation of CSC；2) SWCNT and its derivative can significantly improve sensitiveness of the tumor microenvironment inner tumour cell to chemotherapeutics, promote killing of the chemotherapeutics to it；3) SWCNT and its derivative can significantly reduce multiplication capacity of CSC quantity, microvessel density and tumour cell in tumor tissues etc., and suppress the growth of tumour；4) SWCNT and its derivative can significantly inhibit the expression in TGF signal betas path and downstream and related gene, and then destroy CSC and rely the tumor microenvironment of presence.Material preparation method of the invention is simple, low cost, it is easy to operate, and the water phase SWCNT and its selectively targeted tumor microenvironment of derivative energy for obtaining, and suppresses CSC cell masses, is with a wide range of applications in the treatment of tumour.
Description
Technical field
It is used for oncotherapy the present invention relates to a kind of inorganic nano material, more particularly to a kind of SWCNT and its derivative exist
Destruction tumor microenvironment, suppression TGF signal betas path, suppression tumor stem cell, reduction microvessel density and tumor cell proliferation
Ability, increase tumour cell are to the application in chemotherapy drug susceptibility and oncotherapy.
Background technology
Tumor stem cell (CSC) is the tumour cell that a group has stem-like cell feature in tumor tissues, in the hair of tumour
Vital effect is played in raw, development and pernicious transfer.CSC has the tolerance of height to chemotherapeutics, can
Hide the killing of chemotherapeutics.At present, clinically conventional tumor therapeuticing method chemotherapy, can only remove common tumour cell,
But the CSC in tumour can not be effectively killed, this is the key reason for causing tumor recurrence and Endodontic failure.Therefore, in the urgent need to
The new therapeutic strategy of design comes selectively targeted and removes CSC, and then reaches final preferably therapeutic effect.With traditional chemotherapy
Medicine is compared, the unique physicochemical property of nano material make it have more preferable biocompatibility, dissolubility, targeting, through blood
The ability of brain barrier and cell membrane, stronger plasticity and light thermal property etc., have in targeting with killing CSC and well should
Use prospect.
Now, nano material is commonly used for pharmaceutical carrier and carrys out targeted therapy CSC, such as target CSC marks (CD44,
CD90, CD133 etc.) or targeting press down with the performance-relevant signal paths of CSC (TGF β, Wnt/ β-catenin, Notch etc.)
The self-renewing of CSC processed and Multidirectional Differentiation.However, in the evolution of tumour, CSC Populations are not unalterable
, under the influence of specific tumors microenvironment, common tumour cell can gradually obtain dryness and be dedifferentiated into CSC, and then accelerate
The malignant progression of tumour, makes more tumour cells obtain chemotherapy tolerance, so as to escape killing of the classic chemotherapy to it.Cause
This, tumoricidal microenvironment, the Common tumors cell acquisition dryness that suppresses are likely to become the side of more effective treatment tumour
Method.At present, both at home and abroad have labs correlative study, such as the nano materials of Gd@C82 (OH) 22 can suppress epithelial cell-
Mesenchymal cell changes (EMT), so that suppressing breast epithelium cancer cell obtains CSC features, effectively reduces CSC quantity and suppresses swollen
Knurl grows.
Research finds that the expressions of TGF β 1 are extremely high in kinds of tumors, and the signal paths of TGF β 1 are to tumor microenvironment
Formed and the generation development of tumour is most important.Existing numerous studies show that TGF β 1 are a kind of strong EMT inducing agents, energy
The tumour cell of epithelial origin is enough promoted to obtain CSC characteristics, and it is closely related with the malignant transformation of tumour cell.Osteosarcoma is originated
It is a kind of grade malignancy primary bone tumor very high in mescenchymal stem cell or osteoprogenitor cells.Develop in osteosarcoma
During, tumour cell constantly invades the bone matrix of surrounding, while substantial amounts of TGF β 1 in bone matrix are discharged, progressively shape
The microenvironment of osteogenic sarcoma.Nearest research finds that TGF β 1 can also induce osteosarcoma cell to dedifferente, make common osteosarcoma
Cells switch osteogenic sarcoma stem cell, i.e. CSC cells, so as to accelerate the malignant progression of osteosarcoma.Patients with Osteosarcoma easily occurs
Lung metastases, patient's poor prognosis after transfer and survival rate is low.At present, the evil of osteosarcoma is clinically still suppressed without targeted drug
Property progress.Therefore, the targeting of regulation and control and osteosarcoma stem cell that TGF β 1 can be used for osteosarcoma microenvironment as therapy target is controlled
Treat.
SWCN (SWCNT) has a good application prospect in biomedicine field, such as the diagnosis of disease with
Treatment, biology sensor etc..In oncotherapy, SWCNT is widely used as pharmaceutical carrier, for target and drug delivery, so
And itself influence to cancer cell and the effect in cancer development are also not very clear.In the present invention, we are with bone
Illustrate that SWCNT and its derivative specificity can suppress Common tumors cell de-differentiation formation CSC in vitro as a example by sarcoma, reduce swollen
The quantity and tumor microvessel density of CSC in tumor tissue, and then suppress the growth of tumour.SWCNT and its derivative can show simultaneously
Write and suppress the signal paths of TGF β 1, and then destroy tumor microenvironment, the formation of CSC and the purpose for the treatment of tumour are suppressed so as to reach.
At present, both at home and abroad also without other on SWCNT and its derivative in itself can the selectively targeted signals of suppressions CSC and TGF β 1 it is logical
The report on road.
The content of the invention
It is an object of the invention to provide a kind of carbon nanomaterial SWCNT and its derivative be used to suppressing tumor stem cell and
The application in tumor is prepared, technical problem to be solved is the carbon nanomaterial of the aqueous-phase suspending of synthesizing stable
SWCNT and its derivative.Compared with traditional cancer treatment drugs, the material can suppress the formation of CSC, in reduction tumor tissues
The quantity of CSC, microvessel density and tumor cell proliferation ability etc., suppress TGF signal beta paths, destroy tumor microenvironment, suppression
Tumour growth processed.The nano material can be used as CSC inhibitor for the treatment of tumour, improve the therapeutic effect of tumour.
The present invention is achieved by the following technical solutions.
The present invention provides a kind of application of SWCNT and its derivative in terms of specificity suppresses tumor stem cell (CSC).
In addition, the present invention also provides a kind of SWCNT and its derivative is suppressing TGF signal betas path and destruction tumour micro-loop
Application in border.
The present invention also provides a kind of application of SWCNT and its derivative in tumor is prepared.
The application of the embodiment of the present invention, the derivative includes SWCNT-Raw and SWCNT-COOH.
The application of the embodiment of the present invention, the synthetic method of the SWCNT-Raw and SWCNT-COOH is：
1) SWCNT-Raw and SWCNT-COOH are dissolved in ultra-pure water respectively, are filled with probe type ultrasonic instrument ultrasound to material
Dispersion, is then optionally added into the hydrochloric acid of final concentration of 1-6M；
2) ultrasonic, the nano material that by centrifugation goes out in solution fully dispersed to material is continued in instrument is cleaned by ultrasonic
Precipitation, is then cleaned multiple times precipitation with ultra-pure water, finally resuspended with a small amount of ultra-pure water, using being cleaned by ultrasonic instrument ultrasonic method by its point
Dissipate in water, the final nano material for obtaining stable suspersion in water, and concentration is about 100-150 μ g/mL.
The application of the embodiment of the present invention, including：
1) suppress the method that CSC is formed, it is found that SWCNT and its derivative can significantly inhibit the formation of CSC；
2) SWCNT and its derivative can significantly improve sensitiveness of the tumor microenvironment inner tumour cell to chemotherapeutics, promote
Enter killing of the chemotherapeutics to it；
3) to significantly reduce CSC quantity in tumor tissues, tumor microvessel density and tumour thin for SWCNT and its derivative
Multiplication capacity of born of the same parents etc., and suppress the growth of tumour；
4) SWCNT and its derivative can significantly inhibit the expression of the related gene of TGF signal betas path and downstream, and then broken
Bad CSC is rely the tumor microenvironment of presence.
By above-mentioned technical proposal, the invention has the advantages that：
1) carbon nanomaterial preparation condition used in the present invention and step are simple, it is easy to operate, be combined to industry
Prospect；
2) carbon nanomaterial prepared in the present invention has biocompatibility higher, and specific can suppress CSC's
Formed；
3) carbon nanomaterial prepared in the present invention can significantly inhibit CSC in tumor tissues, reduce microvessel density
With tumor cell proliferation ability etc., suppress tumour growth；
4) carbon nanomaterial prepared in the present invention can effectively suppress TGF signal beta paths, destroy tumor microenvironment, can
The reagent as selectively targeted suppression CSC and TGF signal beta paths is expected to, for oncotherapy.
Brief description of the drawings
Fig. 1 is that water phase SWCNT and its derivative aqueous solution (A) and TEM characterize (B).
Fig. 2 is nano material to HF (A) and the CCK8 results of Common tumors cell (B).
Fig. 3 is that nano material enters tumour cell biological electron microscope picture, and green arrow meaning is intracellular nanometer material
Material.
Fig. 4 is that nano material suppression tumour cell dedifferentes to form CSC sacculus (A) and CSC marker proteins expression (B),
Cell clonality (C) and fat induction differentiation capability (D) are reduced, does not influence chemotherapeutics to kill Common tumors cell
Wound (E), increases killing (F) of the chemotherapeutics to drug tolerance tumour cell in microenvironment.
Fig. 5 is the influence of the formation CSC sacculus that nano material is dedifferented to tumour cell under hypoxemia and acid condition.
Fig. 6 is that nano material dedifferentes the influence to form CSC sacculus to other tumor cell lines.
Fig. 7 is nano material administration time and number of times (A), and to tumor tissues inner tumour cell propagation, (Ki-67 expresses water
It is flat) and microvessel density (CD31) influence (B), and reduce interior CSC abilities (D) of tissue.
Fig. 8 is nano material to TGF beta receptors TGF β RI in TGF signal betas path in tumour cell and downstream smad2 phosphoric acid
The influence (B) of the expression of change level (A) and downstream and CSC performance related genes, nano material is to TGF β RI in tumor tissues
With the influence (D) of the expression of downstream smad2 phosphorylation levels (C) and downstream gene.
Specific embodiment
Application of the invention is described in further detail below by way of specific preferred embodiment combination accompanying drawing, but the present invention
It is not limited in following embodiment.
A kind of carbon nanomaterial SWCNT of the invention and its derivative bag aqueous phase SWCNT-Raw and SWCNT-COOH,
MWCNT is control material, and the synthetic method of SWCNT-Raw, SWCNT-COOH and MWCNT is：
1) by 5-10mg SWCNT-Raw, SWCNT-COOH and MWCNT is dissolved in ultra-pure water 10-20mL respectively, with probe
After formula Ultrasound Instrument ultrasonic disperse, the hydrochloric acid of final concentration of 1-6M is added；
2) it is being cleaned by ultrasonic in instrument after continuation ultrasonic disperse, the nano material gone out in solution by centrifugation is precipitated, so
Precipitation is cleaned multiple times with ultra-pure water afterwards, it is finally resuspended with ultra-pure water, it is dispersed in water using instrument ultrasonic method is cleaned by ultrasonic, most
Nano material of the stable suspersion in water is obtained eventually, and concentration is about 100-150 μ g/mL.
The nano particle prepared in the present invention is characterized using transmission electron microscope (TEM) method；Cell CCK8 experiment inspections
Measure and monitor the growth of standing timber the biocompatibility of material；Differentiation, chemotherapeutics are induced by cell self-renewal, cellular immunofluorescence, fat cell
The methods such as sensitiveness detect that the nano material suppresses tumour cell and dedifferentes to form CSC abilities；Using mouse tumor model, tumour
The methods such as histogenic immunity group, tumor tissues immunofluorescence analyze the nano material and suppress CSC and to tumour in tumor tissues
Therapeutic effect；Suppression by the experimental studies such as RT-PCR, Western blot nano material to the signal paths of TGF β 1 is made
With.
Specific testing result is as follows respectively：
1) TEM of nano materials is characterized
The TEM pictures (Fig. 1) of the nano material for suspending in water of synthesis show, the SWCNT-Raw being dispersed in water with
SWCNT-COOH nano particles length is 1-3 μm, and outside dimension is 1-2nm.
2) biocompatibility analysis
CCK8 test result indicate that, the HF of the SWCNT-Raw and SWCNT-COOH of 0-10 μ g/mL treatment and
Common tumors cell keeps survival rate (Fig. 2) higher, illustrates that the nano material has good biocompatibility.
3) nano material enters cell analysis
Cell biological Electronic Speculum test result indicate that, SWCNT-Raw and SWCNT-COOH can enter tumour cell in (Fig. 3).
4) tumour cell dedifferentes to form CSC detections
Dedifferente to form CSC using the tumour cell (MNNG/HOS) of the induction free serum cultures of TGF β 1, pasted in Induction Process
Parietal cell can gradually change and form CSC sacculus.SWCNT (SWCNT-Raw and SWCNT-COOH) can significantly inhibit CSC sacculus
Form and suppress the expression of CSC marks, and the cell self-renewal ability (clonality) of SWCNT treatment, be divided into
The ability and chemotherapy drug susceptibility of fat cell are similar to Common tumors cell (Fig. 4), show that SWCNT is effectively inhibited
The tumour cell of the inductions of TGF β 1 dedifferentes to form CSC processes.
In hypoxemia or acidic micro-environment, the tumour cell that SWCNT still can suppress the inductions of TGF β 1 dedifferentes to be formed
CSC processes (Fig. 5).In other tumor cell lines (Saos-2 and MG63), SWCNT has same inhibition (Fig. 6).Control
Material MWCNT does not influence then on the process of dedifferenting.
5) vivo tumor model experiment detection
MNNG/HOS cell muscles are injected to mouse leg, diameter of tumor size is treated in 1cm or so, SWCNT is direct
It is expelled in tumor tissues, after processing 31 days, tumor tissues is taken out and coherent detection is carried out.SWCNT can significantly inhibit tumour
Growth, and reduce propagation, tumor microvessel density and the CSC Populations (Fig. 7) of tissue inner tumour cell.
6) signal paths of TGF β 1 analysis
Cell culture invitro and the inductions of TGF β 1 CSC experimental results show that SWCNT can significantly inhibit the signal path mistakes of TGF β 1
The expression (Fig. 8) of journey and downstream gene.Vivo tumor model experimental result explanation SWCNT can suppress TGF β in tumor tissues
The expression (Fig. 8) of 1 signal path process and downstream gene.
Embodiment 1
SWCNT-Raw, SWCNT-COOH and MWCNT 5-10mg are dissolved in ultra-pure water respectively, it is super with probe type ultrasonic instrument
After sound dispersion, the hydrochloric acid of final concentration of 1-6M is added.It is being cleaned by ultrasonic in instrument after continuation ultrasonic disperse, is being gone out by centrifugation molten
Nano material precipitation in liquid, is then cleaned multiple times precipitation with ultra-pure water, finally resuspended with a small amount of ultra-pure water, using ultrasonic cleaning
Instrument ultrasonic method is dispersed in water, the final nano material for obtaining stable suspersion in water, and concentration is about 100-150 μ g/
mL。
By osteosarcoma cell MNNG/HOS cultures in serum free medium, when cell is in exponential phase, respectively
Add 5-10 μ g/mL SWCNT-Raw, SWCNT-COOH and MWCNT to be incubated 24 hours, collect cell and cell is placed in 2%
Stood overnight in glutaraldehyde.Then, cell fixes 1 hour after 1% four three osmiums of oxidation, is prepared after gradient alcohol dehydration ultra-thin
Electron microscopic section.After ultra-thin section is dyeed through uranyl acetate and lead citrate, observation under transmission electron microscope is placed in.As shown in figure 3,
SWCNT-Raw, SWCNT-COOH and MWCNT can be found (shown in green arrow) in MNNG/HOS cytoplasm, and this says
Bright three kinds of nano materials can be absorbed by tumour cell well.
Embodiment 2
According to existing research report, common osteosarcoma cell can be dedifferented in the presence of TGF β 1, formed
CSC.We illustrate that SWCNT and its derivative are dedifferented and CSC shapes to osteosarcoma cell by taking osteosarcoma cell MNNG/HOS as an example
Into inhibitory action.By MNNG/HOS cultures in the serum free medium containing 4ng/mLTGF β 1, while adding respectively different
SWCNT-Raw, SWCNT-COOH and MWCNT treatment of concentration.As shown in Figure 4 A, after 5 days, SWCNT-Raw and
SWCNT-COOH can significantly inhibit the formation of sacculus sample CSC, and this inhibitory action with SWCNT nano material concentration
Raise and strengthen.And could not then be shown as the MWCNT of control material osteosarcoma cell is dedifferented and CSC formed suppression
Make and use.As shown in Figure 4 B, compared with control group (Control), SWCNT-COOH can significantly inhibit MNNG/HOS cell tables
Marker gene c-Kit, stro-1, TRA-1-60, SSEA1 and SSEA4 up to osteosarcoma CSC.As shown in Figure 4 C, TGF β 1 are processed
The clonality of MNNG/HOS cells is significantly stronger than the common MNNG/HOS cells (Adherent) of before processing afterwards, but adds
After entering SWCNT-COOH, TGF β 1 are suppressed significantly to the castering action of MNNG/HOS Cell clonalities.Meanwhile, also show
Work inhibits the ability (Fig. 4 D) of the MNNG/HOS cell differentiation lipoblasts after the treatment of TGF β 1.The explanation of these results,
The MNNG/HOS cells that SWCNT and its derivative SWCNT-COOH can effectively suppress the effects of TGF β 1 obtain CSC characteristics, such as
The expression of CSC surface marker genes, self-renewal capacity and Multidirectional Differentiation ability.
By the ultra-pure water (control) of SWCNT-Raw, SWCNT-COOH or same volume respectively with the chemotherapy of various dose
Drug adriamycin (adriamycin) is jointly processed by the MNNG/HOS cells of adhere-wall culture after 24 hours, using CCK8 reagent analysis
The quantity of living cells.As shown in Figure 4 E, SWCNT and its derived material have no effect on common MNNG/HOS cells to chemotherapeutic to result
The sensitiveness of thing.Then, by the ultrapure of SWCNT-Raw and TGF β 1, SWCNT-COOH and TGF β 1, TGF β 1 or same volume
Water (control) processes the MNNG/HOS cells of free serum culture, and TGF β 1 can promote cell de-differentiation to form CSC after 5d, while
Each group adds the chemotherapeutics of various dose.After treatment 24 hours, using the quantity of CCK8 reagent analysis living cells.Result is as schemed
Shown in 4F, compared with control group (Control), after TGF β 1 make MNNG/HOS cell de-differentiations form CSC, greatly improve thin
Born of the same parents are to the tolerance of chemotherapeutic drugs Doxorubicin, and SWCNT and its derivative significantly reduce the MNNG/HOS cells of the inductions of TGF β 1
Chemotherapy tolerance.The explanation of these results, SWCNT and its derived material can destroy the microenvironment of osteosarcoma cell, so as to carry
Sensitiveness of the tumour cell to chemotherapeutics is risen, strengthens therapeutic effect.
Embodiment 3
MNNG/HOS cell culture is simulated the micro- of intra-tumor acidity in the serum free mediums of pH 6.4 containing TGF β 1
Environment；Culture is in 3%O while by MNNG/HOS cell culture in the PH7.4 serum free mediums containing TGF β 12It is low
In oxygen incubator, the microenvironment of intra-tumor hypoxemia is simulated；Being separately added into SWCNT-Raw, SWCNT-COOH in the medium is carried out
The ultra-pure water of same volume is added in treatment, control group (Control).After 3 days or 5 days, as shown in figure 5, and control group
(Control) compare, SWCNT and its derivative can significantly inhibit MNNG/HOS cells under the conditions of acid and two kinds of hypoxemia
Dedifferente to form sacculus shape CSC.This explanation, SWCNT tumour cell is dedifferented and tumor stem cell formation suppression make
With being not limited only under normal condition, acid and hypoxemia the extreme microenvironment of intra-tumor is also applied for.
Embodiment 4
Osteosarcoma cell line Saos-2, MG-63 are cultivated in the serum free medium containing TGF β 1 respectively, while
SWCNT-Raw, SWCNT-COOH treatment are added in experimental group respectively, the middle addition same volume of control group (Control)
Ultra-pure water.After 5 days, as shown in fig. 6, compared with control group (Control), SWCNT and its derivative can significantly inhibited
Saos-2 forms sacculus shape CSC with MG-63 cell de-differentiations.This explanation, SWCNT and its derived material can suppress various kindred
Oncocyte is dedifferented, and osteosarcoma cell is dedifferented to form the inhibitory action of CSC and have general applicability.
Embodiment 5
By 4 × 106MNNG/HOS cells are seeded in 4~5 weeks BALB/c nude mice leg muscles of size, make it into knurl.
When longest diameter of tumor is up to 1.0cm or so, according to the time shaft shown in Fig. 7 A, by 6 μ g SWCNT-COOH, MWCNT with it is ultrapure
Water (Control) distinguishes direct injection to intra-tumor.Every other day mouse is weighed, and measures the volume of mouse tumor.
As shown in Figure 7 B, the volume growth of SWCNT-COOH group mouse tumors is significantly less than MWCNT groups and ultra-pure water control group (figure to result
8C), and MWCNT groups are with control group that there was no significant difference.This explanation SWCNT-COOH specific can suppress kindred in Mice Body
The growth of knurl.
Then, we carry out HE dyeing and immunohistochemical analysis, as a result as seen in figure 7 c, SWCNT- to mouse tumor tissue
CD31 around necrotic area in COOH treatment group tumor tissues+Blood vessel (green arrow) density is substantially less than MWCNT groups and ultra-pure water
Control group, while significantly reducing the expression of cell propagation marker gene Ki67.What is more important, SWCNT-COOH treatment groups
The expression of CSC surface markers gene c-Kit, stro-1, TRA-1-60, SSEA1 and SSEA4 shows around necrotic area in tumor tissues
Writing reduces (Fig. 7 D), and this explanation SWCNT-COOH significantly reduces the quantity of CSC in tumor tissues stem cell pool.
Embodiment 6
In order to further elucidate the influence of SWCNT and its derivative to the signal paths of TGF β 1 in osteosarcoma microenvironment, we
By MNNG/HOS cell culture in serum free medium, and carry out following treatment：
1) same volume ultra-pure water, 2 are added) add TGF β 1 and same volume ultra-pure water, 3) addition TGF β 1 and SWCNT-
COOH, 4) addition TGF β 1 and SWCNT-Raw, 5) addition TGF β 1 and MWCNT, after 24 hours, collect cell and use western
The experimental technique of blot detects the phosphorylation activity of TGF β1receptors TGF β R1 and downstream effect molecule Smad2.
As shown in Figure 8 A, SWCNT and its derivative SWCNT-COOH significantly reduce the phosphorylation work of TGF β R1 and Smad2
Property.Additionally, we further analyze the signal path downstreams of TGF β 1 and cell transformation and the closely related gene of stem cell properties
The expression of Hey1, Snail1 and Sanil2.QRT-PCR results show (Fig. 8 B) that SWCNT and its derivative SWCNT-COOH are notable
Reduce the expression of Hey1, Snail1 and Sanil2 of the inductions of TGF β 1 in MNNG/HOS cells.Then, we further analyze
SWCNT is in vivo to the influence of TGF β 1 signal paths activity.It is small after by SWCNT-COOH, MWCNT and ultrapure water process
Mouse tumor tissues carry out Western blot detections, as a result find that SWCNT-COOH significantly reduces tumour compared with control group
The phosphorylation activity (Fig. 8 C) of TGF β R1 and Smad2 in tissue, and the signal path downstreams of TGF β 1 are special with cell transformation and stem cell
The expression of property closely related gene Hey1, Snail1 and Sanil2 is significantly reduced (Fig. 8 D).And control material MWCNT is then not
TGF β1receptors and its downstream effect molecule, the expression of target gene can be influenceed.This explanation, SWCNT-COOH can be destroyed specifically
The microenvironment of osteosarcoma cell, suppresses the activity of the signal paths of TGF β 1 in tumour cell.
The above, is only presently preferred embodiments of the present invention, and any formal limitation is not made to the present invention, therefore
It is every without departing from technical solution of the present invention content, any simply repaiied according to what technical spirit of the invention was made to above example
Change, equivalent variations and modification, still fall within the range of technical solution of the present invention.
Claims (6)
1. the application of a kind of SWCNT and its derivative in terms of specificity suppresses tumor stem cell (CSC).
2. the application of a kind of SWCNT and its derivative in TGF signal betas path and destruction tumor microenvironment is suppressed.
3. the application of a kind of SWCNT and its derivative in tumor is prepared.
4. the application according to claim 1 or 2 or 3, it is characterised in that：The synthetic method of the SWCNT and its derivative
For：
1) SWCNT and its derivative are dissolved in ultra-pure water respectively, it is fully dispersed to material with probe type ultrasonic instrument ultrasound, then
It is optionally added into the hydrochloric acid of final concentration of 1-6M；
2) continue ultrasonic fully dispersed to material in instrument is cleaned by ultrasonic, the nano material gone out in solution by centrifugation is sunk
Form sediment, precipitation then is cleaned multiple times with ultra-pure water, it is finally resuspended with a small amount of ultra-pure water, disperseed using instrument ultrasonic method is cleaned by ultrasonic
Yu Shuizhong, the final nano material for obtaining stable suspersion in water, and concentration is about 100-150 μ g/mL.
5. application according to claim 4, it is characterised in that：The SWCNT being dispersed in water and its derivative of synthesis receive
Rice grain length is 1-3 μm, and outside dimension is 1-2nm.
6. the application according to claim 1 or 2 or 3, it is characterised in that including：
1) SWCNT and its derivative can significantly inhibit the formation of CSC；
2) SWCNT and its derivative can significantly improve sensitiveness of the tumor microenvironment inner tumour cell to chemotherapeutics, promotionization
Treat killing of the medicine to it；
3) SWCNT and its derivative can significantly reduce the increasing of the CSC quantity, microvessel density and tumour cell in tumor tissues
Ability etc. is grown, and suppresses the growth of tumour；
4) SWCNT and its derivative can significantly inhibit the expression in TGF signal betas path and downstream and related gene, and then destroy
CSC is rely the tumor microenvironment of presence.
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