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CN104692343A - Tin selenide nano material, preparation method and application thereof - Google Patents

Tin selenide nano material, preparation method and application thereof Download PDF

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Publication number
CN104692343A
CN104692343A CN201510114830.1A CN201510114830A CN104692343A CN 104692343 A CN104692343 A CN 104692343A CN 201510114830 A CN201510114830 A CN 201510114830A CN 104692343 A CN104692343 A CN 104692343A
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nano material
tin diselenide
tin
thermal
medicine
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CN104692343B (en
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杨黄浩
张晓龙
郑琤
梁虹
王丽萍
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Fuzhou University
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Fuzhou University
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    • CCHEMISTRY; METALLURGY
    • C01INORGANIC CHEMISTRY
    • C01BNON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B19/00Selenium; Tellurium; Compounds thereof
    • C01B19/007Tellurides or selenides of metals
    • CCHEMISTRY; METALLURGY
    • C01INORGANIC CHEMISTRY
    • C01PINDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2002/00Crystal-structural characteristics
    • C01P2002/70Crystal-structural characteristics defined by measured X-ray, neutron or electron diffraction data
    • C01P2002/72Crystal-structural characteristics defined by measured X-ray, neutron or electron diffraction data by d-values or two theta-values, e.g. as X-ray diagram
    • CCHEMISTRY; METALLURGY
    • C01INORGANIC CHEMISTRY
    • C01PINDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2002/00Crystal-structural characteristics
    • C01P2002/80Crystal-structural characteristics defined by measured data other than those specified in group C01P2002/70
    • CCHEMISTRY; METALLURGY
    • C01INORGANIC CHEMISTRY
    • C01PINDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2004/00Particle morphology
    • C01P2004/01Particle morphology depicted by an image
    • C01P2004/04Particle morphology depicted by an image obtained by TEM, STEM, STM or AFM
    • CCHEMISTRY; METALLURGY
    • C01INORGANIC CHEMISTRY
    • C01PINDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2004/00Particle morphology
    • C01P2004/60Particles characterised by their size
    • C01P2004/62Submicrometer sized, i.e. from 0.1-1 micrometer
    • CCHEMISTRY; METALLURGY
    • C01INORGANIC CHEMISTRY
    • C01PINDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2004/00Particle morphology
    • C01P2004/60Particles characterised by their size
    • C01P2004/64Nanometer sized, i.e. from 1-100 nanometer
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00Technologies relating to chemical industry
    • Y02P20/10Process efficiency
    • Y02P20/129Energy recovery, e.g. by cogeneration, H2recovery or pressure recovery turbines

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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Inorganic Chemistry (AREA)

Abstract

The invention discloses a tin selenide nano material, a preparation method and application thereof. Tin selenide is synthesized by utilizing a simple, mild and green method, further, hydrophilic ligands are modified in an ultrasonic method and tin selenide nano-sheets with good water dispersibility are synthesized. The nano material has strong near-infrared absorption property and is capable of converting effective near-infrared laser into thermal energy; the photo-thermal conversion efficiency is up to 29.8%; meanwhile, the nano material has good photo-thermal stability and can be applied to light-heat treatment for cancer cells. Meanwhile, the nano material has big specific surface area of a two-dimensional laminated structure and higher medicine-carrying capacity; the nano medicine complex is capable of realizing medicine release effects of pH value response and photo-thermal response and can be utilized as a medicine carrier for chemotherapy of cancer cells. The nano material can be applied to photoacoustic imaging and infrared thermal imaging and realizes photo-thermal and medicine integrated treatment of imaging guidance.

Description

A kind of Tin diselenide nano material and its preparation method and application
Technical field
The invention belongs to nano material preparation and biomedical sector, be specifically related to a kind of Tin diselenide nano material and its preparation method and application.
Background technology
In recent years, nano material more and more causes the attention of researchist in the application of biomedical sector, has become an important directions of Nano-technology Development.Nano material being introduced biomedicine and likely in single system, realize several functions simultaneously, is one of the important development trend in nanosecond medical science field.This multi-functional nanometer material namely in single nano material simultaneously integrated multiple object as while imaging and treatment or integrate multiple parts to realize plurality of target function to realize some Premium Features, the side effect that can reduce repeatedly diagnosis and treatment reaches better treatment effect.
Near infrared light has the advantage of dark penetration into tissue and minimum tissue injury.When target tumor position, the near infrared luminous energy of absorption can be converted to heat energy and be used for photo-thermal therapy or can produce the real time imagery that ultrasonic wave is used for tumor tissues simultaneously by the diagnosis and treatment reagent of near infrared light response.Therefore, based on the nano material that single near infrared light responds, can realize Real-Time Optical and respond into picture (as photoacoustic imaging(PAI), optical imagery) and the treatment of photoresponse simultaneously (as photo-thermal therapy, optical dynamic therapy, light inspire chemotherapy), be the very promising diagnosis and treatment material of a class.
The group IV-VI series semiconductor material of narrow band gap, as SnS, SnSe, GeS, GeSe, PbS, PbSe, is with a wide range of applications in photovoltaic solar cell, near infrared light electric installation, memory switch device, lithium ion battery material, catalysis etc.The band gap that Tin diselenide has large uptake factor and superposes with solar spectrum, being regarded as may replacer relative to the low toxicity of the narrow band gap nano material of leaded and cadmium and environmental friendliness.
Up till now, the synthesis Tin diselenide nanometer sheet method of bibliographical information, general needs the equal organic-inorganic of high temperature oleyl amine participation or use organic selenium source, make that synthetic operation requirement is high, synthesis is inconvenient or cost is high, biomedicine to be applied in addition and need more loaded down with trivial details surface-functionalized operation, limit these methods in biomedical further application.Therefore, develop a kind of more easy method and adopt the inorganic selenium source of more low cost to synthesize Tin diselenide nano material, and rationally carry out modified biological consistency part, develop its application in biomedical diagnosis and treatment and there is important using value.
Summary of the invention
The object of the present invention is to provide a kind of Tin diselenide nano material and its preparation method and application.Obtained Tin diselenide nanometer sheet (SnSeNSs) can be used for photo-thermal therapy, photoacoustic imaging(PAI), the infrared thermal imaging of cancer cells.Simultaneously, this nano material has two-dimentional laminated structure, large specific surface area, have high drug carrying capacity, its Nano medication complex body can realize the drug release of acid ph value response and photothermal response, can be used as the chemotherapy that pharmaceutical carrier is applied to tumour or disease cells.
For achieving the above object, the present invention adopts following technical scheme:
The particle diameter of Tin diselenide nano material is a 20-500 nanometer, finishing biocompatible hydrophilic part.
Described biocompatible hydrophilic part is one or more in polyacrylic acid, polyvinylpyrrolidone, polymine, polyoxyethylene glycol, hyaluronic acid, chitosan, Fucose, dextran, albumin, gelatin, liposome.
Preparation method comprises the following steps:
(1) in water, add selenium powder, then add sodium hydroxide, stir and selenium powder is dissolved;
(2) citric acid is dissolved in the water, adds SnCl 22H 2o, ultrasonic making it is dissolved completely;
(3) under fast stirring, the solution that step (2) is obtained is added drop-wise in the obtained solution of step (1);
(4), after reaction terminates, room temperature is cooled to, centrifugal, be washed to clear liquid in neutral;
(5) in biocompatible hydrophilic part, the Tin diselenide material that step (4) obtains is added, supersound process, centrifugal removing bulk Tin diselenide material; Collect upper solution, then the Tin diselenide nano material that collected by centrifugation biocompatible hydrophilic is ligand modified, after washing three times, be again scattered in water and preserve.
In step (1), the mol ratio of selenium powder and sodium hydroxide is 0.1-1:1-40, and volume of water is 1-10 times of sodium hydroxide weight.
SnCl in step (2) 22H 2the mol ratio of O and citric acid is 0.1-1:1-20, and the volume of water is 0.5-10 times of citric acid weight.
Described Tin diselenide nano material as pharmaceutical carrier, by adsorption carrying medicament bioactive molecule.
Described pharmaceutical activity molecule is one or more in cancer therapy drug, microbiotic, Interferon, rabbit, tumour necrosis factor, proteinase inhibitor, labelled with radioisotope composition, antisense nucleic acid, tiny RNA, antibody, gastrointestinal system medicine, optical dynamic therapy medicine.
Described cancer therapy drug is one or more in Zorubicin, taxol, phthalocyanine, camptothecine, epirubicin, cis-platinum, carboplatin, anti-platinum, docetaxel, daunorubicin, bleomycin, vinealeucoblastine(VLB), methotrexate gemcitabine, Etoposide, tamoxifen.
Remarkable advantage of the present invention is:
(1) the simple gentleness of Tin diselenide nano material preparation process, less energy-consumption, easily mass-producing in the present invention;
(2) in the present invention, ligand modified Tin diselenide nano material has had biocompatibility, strong near infrared absorption, photo-thermal conversion efficiency reaches 29.8%, and has good photo and thermal stability simultaneously, can be used for photo-thermal therapy, photoacoustic imaging(PAI), infrared thermal imaging;
(3) in the present invention, Tin diselenide nano material has two-dimentional laminated structure, large specific surface area, and can realize high drug molecule and can't harm load, mode of loading is suction type, avoids the destruction of covalent modification process to drug molecular structure;
(4) in the present invention, Tin diselenide nano material-drug composite can realize medicament slow release.Drug molecule is by suction type load, and its active substance is easy to discharge from carrier under condition of acidic pH or photothermy, and keeps long slow releasing, can reach and keep drug effect for a long time;
(5) Tin diselenide nano material-drug composite of the present invention possesses the feature such as good stability and long circulating, has outstanding photothermal deformation ability, good drug carrying capacity and passive targeting, biocompatibility, can realize photoacoustic imaging(PAI), infrared thermal imaging, drug delivery chemotherapy to tumour or disease cells or tissue.
Accompanying drawing explanation
Fig. 1 is the transmission electron microscope image of Tin diselenide nanometer sheet.
Fig. 2 (A) figure is the X-ray diffraction image (XRD) of Tin diselenide nanometer sheet, and (B) figure is the X-ray energy dispersion spectrum (EDS) of Tin diselenide nanometer sheet.
Fig. 3 is the visible near-infrared abosrption spectrogram of different concns Tin diselenide nanometer sheet solution.
Fig. 4 is the photo-thermal heating curve variation diagram in time of different concns Tin diselenide nanometer sheet solution.
Fig. 5 is the Cell viability figure of different concns Tin diselenide nanometer sheet solution.
Fig. 6 is that the photo-thermal of different concns Tin diselenide nanometer sheet solution irradiates and the lower Cell viability comparison diagram of unglazed photograph.
The load different concns medicine DOX ability examination of Fig. 7 (A) Tin diselenide nanometer sheet solution and the release dynamics of (B) Tin diselenide nanometer sheet-drug composite under condition of different pH.
Fig. 8 is the photoacoustic imaging(PAI) image of Tin diselenide nanometer sheet solution.
Embodiment
Below by concrete exemplifying embodiment, technical scheme of the present invention is described further, but can not limits the scope of the invention with this.
Embodiment 1:
The preparation of Tin diselenide nano material:
Reaction solution A: the selenium powder taking 0.040g, be added in the ultrapure water of 10 milliliters, taking 5.00 g sodium hydroxide is again added in selenium powder solution, middling speed magnetic agitation is dissolved to selenium powder, can accelerate the dissolving of selenium powder because the heat release of sodium hydroxide dissolution process makes solution temperature rise in this process, last solution is burgundy.Reaction soln B: take 2.00 g citric acids and be fully dissolved in 1 milliliter of ultrapure water, then take 0.21 g tindichloride dihydrate (SnCl 22H 2o) citric acid solution ultrasonic dissolution is added to.Under rapid mixing conditions, negate answers solution B to be added dropwise in reaction soln A, and solution is shoaled gradually by burgundy, and---colourless---brown---brown-black, becomes cotton-shaped and avales.This process shows to define Tin diselenide material.Continue reaction 5 minutes, be cooled to room temperature.Reaction soln is divided into 4 pipes, and 9000 rpms centrifugal 5 minutes, abandoning supernatant, add ultrapure water dispersion, then 9500 rpms centrifugal 5 minutes, repeats this operation and is washed to supernatant liquor pH value for neutral.
Modified biological consistency part: the Tin diselenide material of synthesis to be added in polyacrylic acid (molecular weight 3000) solution of 25 milliliters 10 milligrams every milliliter supersound process 6 hours.After ultrasonic end, elder generation 3000 rpms is centrifugal 5 minutes, discards the Tin diselenide from the bulk of getting off, and collects upper solution; In order to remove excessive polyacrylic acid, again to centrifugal 10 minutes of the solution 9500 rpms collected, collecting precipitation, adds milli-Q water 3 times, precipitation is scattered in 5 milliliters of ultrapure waters, and the dispersion soln getting 1 milliliter carrys out the concentration of Tin diselenide nano material in volumetric soiutions by drying means.The Tin diselenide nano material transmission electron microscope obtained characterizes as shown in Figure 1, illustrates and synthesize laminated structure have the ability for carrying medicament.Carry out XRD and EDS characterization result as shown in Figure 2 to the Tin diselenide nano material obtained, proves that the material synthesized is SnSe, containing selenium and tin element, wherein carbon, oxygen are that modified ligand contains, and copper is copper mesh used when testing.The visible near-infrared absorption spectrum of the Tin diselenide nanometer sheet solution of different concns as shown in Figure 3, illustrates that Tin diselenide nanometer sheet has good near infrared absorption, can be used for photo-thermal therapy, photoacoustic imaging(PAI), infrared thermal imaging application.
Embodiment 2:
The photo-thermal heating curve of test Tin diselenide nanometer sheet solution: the Tin diselenide nanometer sheet solution getting 1 milliliter is to quartz colorimetric utensil (light path 1cm, the area 1cm of constant 2), also record temperature variation with the laser radiation solution of 808 nm simultaneously.Utilize a temperature monitor being furnished with thermopair microprobe (φ=0.5 mm), microprobe is immersed in solution, the microprobe position in the solution direct irradiation that will avoid being subject to laser with contact bottom cuvette or side, to record the temperature of a solution every 1s by connecting software.The photo-thermal heating curve of the Tin diselenide nanometer sheet solution of test different concns: preparation different concns (0-80 μ gmL -1) Tin diselenide nanometer sheet solution, regulate laser power density be 2 Wcm -2, measure the temperature variation curve between 0-600 second of solution under 808 nm laser radiations.Be illustrated in figure 4 the photo-thermal heating curve of corresponding Tin diselenide nanometer sheet solution.Visible Tin diselenide nanometer sheet solution can be rapidly heated under light illumination, is expected to for photo-thermal therapy.
Embodiment 3:
The cytotoxicity of Tin diselenide nanometer sheet is examined or check: by the relative reactivity of CCK-8 method test cell with HepG2 cell.Particularly, the HepG2 cell (about 1 × 10 of exponential phase of growth 4individual every hole) be inoculated in 96 orifice plates the cell culture fluid (the RPMI-1640 substratum containing 10% foetal calf serum, 1% penicillin and 1% Streptomycin sulphate) of hatching in 100 μ L and cultivate at 37 DEG C containing 5% CO 2moistening atmosphere cell culture incubator 24 hours.Afterwards, take out nutrient solution, add the cell culture fluid that 100 μ L contain the Tin diselenide nanometer sheet of different concns, parallel 3 times of each concentration, continues to hatch 24 hours.After pipetting nutrient solution, 2 times are washed with phosphate buffered saline buffer, with reference to the operation of CCK-8 test kit specification sheets, each hole adds 100 uL nutrient solutions and 10 uL CCK-8 solution (the CCK-8 solution of volume of culture 10 %), be positioned over incubator and hatch 1 hour again, test the absorption value of each hole at 450 nm places by microplate reader.The cell not adding Tin diselenide nanometer sheet only to add nutrient solution is 100% survival rate, and the versus cell calculating the Tin diselenide nanometer sheet of each concentration is active.As shown in Figure 5, result display Tin diselenide nanometer sheet reaches 200 μ gmL in concentration to result 1time, it does not still have obvious toxicity for HepG2 cell, illustrates that its biocompatibility is good.
The photo-thermal therapy cytotoxicity of Tin diselenide nanometer sheet: HepG2 cell is inoculated in 96 orifice plates to be cultivated at 37 DEG C containing 5 % CO 2moistening atmosphere cell culture incubator 24 hours.After removing nutrient solution, add 100 μ L and contain different concns (0-60 μ gmL -1) Tin diselenide nanometer sheet, parallel 3 groups, continue cultivation after 6 hours, each hole is 2 Wcm with 808 nm laser power densities -2irradiate 5 minutes, then after cultivating 24 hours, the survival rate of CCK-8 Evaluation cell.Each concentration Tin diselenide nanometer sheet also does 3 groups of not illumination as a comparison simultaneously.Result as shown in Figure 6, along with the increase of Tin diselenide nanometer sheet concentration, at 2 Wcm -2808 nm laser light were shone after 5 minutes, and the survival rate of cell reduces gradually.30 μ gmL are reached in Tin diselenide nanometer sheet concentration -1time, cell has death clearly, at 60 μ gmL -1time the overwhelming majority cell dead after illumination.Illustrate that Tin diselenide nanometer sheet can be used for the photo-thermal therapy of tumour cell.
Embodiment 4:
The drug loading of Tin diselenide nanometer sheet and release: with Zorubicin (DOX) for drug molecule, Tin diselenide nanometer sheet (final concentration 100 μ gmL -1) be mixed in 20 mM phosphoric acid (PB) buffered soln with the DOX of different concns, lucifuge is vibrated 12 hours.Afterwards, 10000 rpms 10 minutes centrifugal, calculate adsorptive capacity by DOX typical curve after the DOX(do not adsorbed of excessive separation collects) and Tin diselenide nanometer sheet-DOX; Tin diselenide nanometer sheet-DOX uses PB solution washing 3 times again, and after dispersion, lucifuge 4 degree preservation is stand-by again.DOX surveys DOX in the adsorptive capacity of Tin diselenide nanometer sheet by UV-Visible spectrophotometer and makes DOX typical curve in the absorption at 490nm place and calculate, and compares the DOX that adds and not by the DOX adsorbed.Tin diselenide nanometer sheet loads DOX capacity calculation formula: W dOX/ W snSeNSs× 100%=(W dOX add-on-W dOX does not adsorb)/W snSeNSs× 100%.Result, as shown in Fig. 7 (A), illustrates the drug carrying capacity that Tin diselenide nanometer sheet is high.
The release dynamics of Tin diselenide nanometer sheet-DOX: get load DOX(600 μ gmL -1) the pH value being scattered in 1 mL respectively of Tin diselenide nanometer sheet-DOX mixture be in the 10 mM PBS buffered soln of 5.0 and 7.4, be positioned over 37 degree of shaking tables 200 rpms shake.Collect clear liquid by after the solution centrifugal of getting 100 uL, the absorption value measuring DOX in clear liquid calculates the release conditions of different time DOX.Result, as shown in Fig. 7 (B), describes Tin diselenide nanometer sheet-DOX mixture, can realize the release of drug molecule under condition of acidic pH.Can be used for tumour cell drug treatment.
Embodiment 5:
Scan with 808 nanometer lasers under the centrifuge tube of the solution that Tin diselenide nanometer sheet is housed being put in photoacoustic imaging(PAI) instrument, carry out photoacoustic imaging(PAI).Result as shown in Figure 8, can find out that the solution of Tin diselenide nanometer sheet has good photoacoustic signal, can be used for photoacoustic imaging(PAI) in tumour cell and tissue.
The foregoing is only preferred embodiment of the present invention, all equalizations done according to the present patent application the scope of the claims change and modify, and all should belong to covering scope of the present invention.

Claims (8)

1. a Tin diselenide nano material, is characterized in that: particle diameter is 20-500 nanometer, finishing biocompatible hydrophilic part.
2. Tin diselenide nano material according to claim 1, is characterized in that: described biocompatible hydrophilic part is one or more in polyacrylic acid, polyvinylpyrrolidone, polymine, polyoxyethylene glycol, hyaluronic acid, chitosan, Fucose, dextran, albumin, gelatin, liposome.
3. prepare a method for Tin diselenide nano material as claimed in claim 1, it is characterized in that: comprise the following steps:
(1) in water, add selenium powder, then add sodium hydroxide, stir and selenium powder is dissolved;
(2) citric acid is dissolved in the water, adds SnCl 22H 2o, ultrasonic making it is dissolved completely;
(3) under fast stirring, the solution that step (2) is obtained is added drop-wise in the obtained solution of step (1);
(4), after reaction terminates, room temperature is cooled to, centrifugal, be washed to clear liquid in neutral;
(5) in biocompatible hydrophilic part, the Tin diselenide material that step (4) obtains is added, supersound process, centrifugal removing bulk Tin diselenide material; Collect upper solution, then the Tin diselenide nano material that collected by centrifugation biocompatible hydrophilic is ligand modified, after washing three times, be again scattered in water and preserve.
4. method according to claim 3, is characterized in that: in step (1), the mol ratio of selenium powder and sodium hydroxide is 0.1-1:1-40, and volume of water is 1-10 times of sodium hydroxide weight.
5. method according to claim 3, is characterized in that: SnCl in step (2) 22H 2the mol ratio of O and citric acid is 0.1-1:1-20, and the volume of water is 0.5-10 times of citric acid weight.
6. a Tin diselenide applications to nanostructures as claimed in claim 1, is characterized in that: described Tin diselenide nano material as pharmaceutical carrier, by adsorption carrying medicament bioactive molecule.
7. application according to claim 6, is characterized in that: described pharmaceutical activity molecule is one or more in cancer therapy drug, microbiotic, Interferon, rabbit, tumour necrosis factor, proteinase inhibitor, labelled with radioisotope composition, antisense nucleic acid, tiny RNA, antibody, gastrointestinal system medicine, optical dynamic therapy medicine.
8. application according to claim 7, is characterized in that: described cancer therapy drug is one or more in Zorubicin, taxol, phthalocyanine, camptothecine, epirubicin, cis-platinum, carboplatin, anti-platinum, docetaxel, daunorubicin, bleomycin, vinealeucoblastine(VLB), methotrexate gemcitabine, Etoposide, tamoxifen.
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