CN106860865B - A kind of Ni0.85Se nano material and its preparation method and application - Google Patents
A kind of Ni0.85Se nano material and its preparation method and application Download PDFInfo
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- 239000002086 nanomaterial Substances 0.000 title claims abstract description 75
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims abstract description 88
- 239000011669 selenium Substances 0.000 claims abstract description 74
- 238000003384 imaging method Methods 0.000 claims abstract description 15
- 239000003446 ligand Substances 0.000 claims abstract description 10
- 238000007626 photothermal therapy Methods 0.000 claims abstract description 8
- 239000003937 drug carrier Substances 0.000 claims abstract description 5
- -1 selenium anion Chemical class 0.000 claims abstract description 3
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 28
- 239000007864 aqueous solution Substances 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 229940009456 adriamycin Drugs 0.000 claims description 12
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 9
- NLZOGIZKBBJWPB-UHFFFAOYSA-N [Na].[SeH2] Chemical compound [Na].[SeH2] NLZOGIZKBBJWPB-UHFFFAOYSA-N 0.000 claims description 7
- 150000002815 nickel Chemical class 0.000 claims description 6
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 6
- 239000012279 sodium borohydride Substances 0.000 claims description 6
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- 230000004048 modification Effects 0.000 claims description 5
- 238000012986 modification Methods 0.000 claims description 5
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- 239000000126 substance Substances 0.000 claims description 5
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 claims description 4
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims description 4
- 239000002246 antineoplastic agent Substances 0.000 claims description 4
- 229940041181 antineoplastic drug Drugs 0.000 claims description 4
- 239000011261 inert gas Substances 0.000 claims description 4
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 claims description 4
- 239000002872 contrast media Substances 0.000 claims description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 2
- 102000009027 Albumins Human genes 0.000 claims description 2
- 108010088751 Albumins Proteins 0.000 claims description 2
- MQRWBMAEBQOWAF-UHFFFAOYSA-N acetic acid;nickel Chemical compound [Ni].CC(O)=O.CC(O)=O MQRWBMAEBQOWAF-UHFFFAOYSA-N 0.000 claims description 2
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 2
- 238000005119 centrifugation Methods 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 229920002674 hyaluronan Polymers 0.000 claims description 2
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- 229940078494 nickel acetate Drugs 0.000 claims description 2
- IPLJNQFXJUCRNH-UHFFFAOYSA-L nickel(2+);dibromide Chemical compound [Ni+2].[Br-].[Br-] IPLJNQFXJUCRNH-UHFFFAOYSA-L 0.000 claims description 2
- BFSQJYRFLQUZKX-UHFFFAOYSA-L nickel(ii) iodide Chemical compound I[Ni]I BFSQJYRFLQUZKX-UHFFFAOYSA-L 0.000 claims description 2
- KBJMLQFLOWQJNF-UHFFFAOYSA-N nickel(ii) nitrate Chemical compound [Ni+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O KBJMLQFLOWQJNF-UHFFFAOYSA-N 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 2
- 229960001603 tamoxifen Drugs 0.000 claims description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims 2
- 108010006654 Bleomycin Proteins 0.000 claims 1
- 229960001561 bleomycin Drugs 0.000 claims 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims 1
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- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
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- A—HUMAN NECESSITIES
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- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/221—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by the targeting agent or modifying agent linked to the acoustically-active agent
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
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- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5138—Organic macromolecular compounds; Dendrimers obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
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- A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
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- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
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Abstract
The invention discloses a kind of Ni0.85Se nano material and its preparation method and application obtains the good Ni of dispersibility by lower valency selenium anion and nickel cation being stirred reaction, is then centrifuged for, dialyses in the presence of hydrophilic ligand0.85Se nano material.Gained nano material of the invention has very strong near infrared absorption characteristic, and near infrared light effectively can be converted into thermal energy, has very strong photothermal conversion efficiency and preferable photo and thermal stability, can be used in the photo-thermal therapy of tumour;And present invention gained nano material is also used as chemotherapy of the pharmaceutical carrier for tumour, or is used for photoacoustic imaging, to realize the combination therapy of imaging guidance photo-thermal therapy and chemotherapy.
Description
Technical field
The invention belongs to nano material preparation and fields of biomedicine, and in particular to a kind of Ni0.85Se nano material and its
Preparation method and application.
Background technique
In recent years, nano material biomedical aspect application obtained the attention of scientist, especially medical diagnosis on disease,
Disease prevention, drug therapy etc. all obtain very big progress.Nano material biomedical aspect development so that single
Realize that multiple functions become possible to simultaneously in system, it is current for can be realized simultaneously the multi-functional nanometer material of diagnosing and treating
One of hot spot of research.The integrated realization of diagnosis and treatment, can significantly improve the therapeutic effect of tumour.
Near infrared light has many advantages, such as that penetration into tissue is strong, almost not damaged to organizing, and is a kind of in field of biomedicine
Ideal light source.Near infrared light needs to there is good absorption to receive near infrared light to play diagnosis and treatment effect in vivo
Rice material convert thereof into thermal energy, so as to for tumor locus photoresponse treatment and real time imagery.It would therefore be highly desirable to develop base
In the nano material of near infrared light response, and possesses it while realizing that (such as optical dynamic therapy, photo-thermal therapy) is treated in photoresponse
With the ability of photoresponse imaging (such as optical imagery, photoacoustic imaging).
Ni0.85Se is a kind of critically important semiconductor material, has excellent electromagnetism and physical and chemical performance, exists
The fields such as solar battery, catalysis, supercapacitor, sensor, conducting material have a wide range of applications.Currently,
Ni0.85The synthetic method of Se mainly has hydrothermal/solvent thermal synthesis method, solid-phase synthesis, ultrasonic, machine-alloying, change
Learn vapour deposition process etc..Complicated synthetic method, cumbersome surface modification, poor biocompatibility etc., limits Ni0.85Se
Application of the nano material in biomedical aspect.Up to the present, there are no Ni0.85Se nano material tumor thermal therapy,
Report in terms of chemotherapy and photoacoustic imaging.Therefore, develop a kind of simple method one-step synthesis favorable dispersibility of green
Ni0.85Se nano material, and its application in biomedical aspect is studied with important researching value.
Summary of the invention
The present invention is to provide a kind of Ni to avoid above-mentioned existing deficiencies in the technology0.85Se nano material and
Preparation method and application, it is intended to which there is the Ni of good biocompatibility and preferably dispersibility by one-step synthesis method0.85Se
Nano material, and it is used for the photo-thermal therapy and chemotherapy and photoacoustic imaging of tumour.
The present invention solves technical problem, adopts the following technical scheme that
The present invention discloses a kind of Ni first0.85Se nano material, partial size are 2~50nm, and there is hydrophilic ligand on surface
Modification.The hydrophilic ligand is at least one of albumin, polyacrylic acid and hyaluronic acid.
Above-mentioned Ni0.85The preparation method of Se nano material, includes the following steps:
(1) under inert gas protection, selenium powder and sodium borohydride are dissolved in water, are uniformly mixed, are then restored to molten
Liquid is colourless, obtains sodium hydrogen selenide solution;
(2) mixed aqueous solution of hydrophilic ligand and nickel salt is added drop-wise in the sodium hydrogen selenide solution, then at room temperature
5min~2h is stirred, centrifugation obtains Ni0.85Se nano material;
(3) by the Ni0.85Se nano material, which is placed in ultrapure water, dialyses for 24 hours, changes a water every 3~4h, that is, obtains
Ni0.85The aqueous solution of Se nano material.
Wherein, the nickel salt is at least one of nickel chloride, nickel acetate, nickel nitrate, nickelous bromide and nickel iodide.
Wherein, the ratio between amount of substance of selenium powder and sodium borohydride is 1:3, and the ratio between nickel salt and the amount of substance of selenium powder are 1:1.
The present invention further discloses above-mentioned Ni0.85Se applications to nanostructures passes through that is, for being used as pharmaceutical carrier
Suction-operated loads anticancer drug;And/or for being used as photo-thermal therapy agent;And/or for the contrast agent as photoacoustic imaging.
Wherein, the anticancer drug is cis-platinum, adriamycin, camptothecine, daunorubicin, vincaleukoblastinum, tamoxifen and Bo Lai
At least one of mycin.
The beneficial effects of the present invention are embodied in:
1, the present invention passes through the one-step synthesis method Ni of favorable dispersibility under conditions of room temperature water phase0.85Se nanometers of materials
Material, synthetic method is simply green, convenient for industrialization;
2, the Ni prepared by the present invention0.85Se nano material has good biocompatibility, has in the near infrared region
Stronger absorption has higher photothermal conversion efficiency, and has good photo and thermal stability, and the photo-thermal that can be used for tumour is controlled
It treats, photoacoustic imaging;
3, the Ni prepared by the present invention0.85Se nano material can be used as pharmaceutical carrier, to anticancer by way of absorption
Drug is loaded, gained Ni0.85Se Nano medication compound has the drug release of pH response, can be used for the chemotherapy of tumour.
Detailed description of the invention
Fig. 1 is that whether there is or not the Ni of hydrophilic ligand modification in embodiment 1 and embodiment 20.85Se nano material is dispersed in water
The comparison of property;
Fig. 2 is 2 gained Ni of embodiment0.85The x-ray diffraction pattern of Se nano material;
Fig. 3 is 2 gained Ni of embodiment0.85The transmission electron microscope picture of Se nano material;
Fig. 4 is various concentration Ni0.85The UV-visible absorption spectrum of the aqueous solution of Se nano material;
Fig. 5 is various concentration Ni0.85The aqueous solution of Se nano material irradiates the heating curve of 10min under 808nm laser
Figure;
Fig. 6 is Ni0.85The aqueous solution of Se nano material irradiates 5 photo-thermal stablizing effect figures repeatedly under 808nm laser;
Fig. 7 is that Ni is injected in Mice Body0.85Photoacoustic imaging comparison diagram before and after Se nano material;
Fig. 8 is free adriamycin, Ni0.85Se Nano medication compound is in the case where pH is 7.4 and 5.0 phosphate buffer
Drug release patterns;
Fig. 9 is mtt assay characterization irradiation front and back free adriamycin, Ni0.85Se nano material and Ni0.85Se Nano medication is compound
Object is to Hela cell activity figure (a is laser irradiation 0min, and b is laser irradiation 5min).
Specific embodiment
Elaborate below to the embodiment of the present invention, following embodiments under the premise of the technical scheme of the present invention into
Row is implemented, and the detailed implementation method and specific operation process are given, but protection scope of the present invention is not limited to following realities
Apply example.
The Ni that embodiment 1, surface are modified without hydrophilic ligand0.85The preparation of Se nano material
(1) under inert gas protection, 0.1mmol selenium powder and 0.3mmol sodium borohydride are dissolved in 80mL water, are mixed
Uniformly, it is colourless to be restored to solution, obtains sodium hydrogen selenide solution;
(2) by the mixed solution of 0.1mmol nickel chloride dissolution 20mL ultrapure water, selenium hydrogen obtained by step (1) is added dropwise
Change sodium solution, stir 5min at room temperature, be centrifuged, obtains Ni0.85Se nano material
(3) by Ni0.85Se nano material, which is placed in ultrapure water, dialyses for 24 hours, changes a water every 3~4h, i.e. acquisition black
Ni0.85The aqueous solution of Se nano material.
The Ni that embodiment 2, surface have polyacrylic acid to modify0.85The preparation of Se nano material
(1) under inert gas protection, 0.1mmol selenium powder and 0.3mmol sodium borohydride are dissolved in 80mL water, are mixed
Uniformly, it is colourless to be restored to solution, obtains sodium hydrogen selenide solution;
(2) 0.1mmol nickel chloride is dissolved in the mixed solution of 100 μ L polyacrylic acid solutions and 20mL ultrapure water, by
It is added dropwise to sodium hydrogen selenide solution obtained by step (1), stirs 5min at room temperature, is centrifuged, Ni is obtained0.85Se nano material
(3) by Ni0.85Se nano material, which is placed in ultrapure water, dialyses for 24 hours, changes a water every 3~4h, i.e. acquisition black
Ni0.85The aqueous solution of Se nano material.
As shown in Figure 1, comparative example 1 (right side sample bottle in figure) and embodiment 2 (left side sample bottle in figure) are obtained
Ni0.85The aqueous solution of Se nano material is it is found that the Ni that surface does not have hydrophilic ligand to modify0.85Se nano material is in water
Dispersibility is very poor, is in precipitated form, and the Ni for having polyacrylic acid to modify0.85Se nano material has good dispersibility in water.
Fig. 2 is 2 gained Ni of embodiment0.85The x-ray diffraction pattern of Se nano material, card corresponding with standard card 18-0888
Bright product is Ni0.85Se。
Fig. 3 is 2 gained Ni of embodiment0.85The transmission electron microscope picture of Se nano material, it can be seen that primer size is uniform, average
Partial size is in 10nm or so.
Fig. 4 is various concentration Ni0.85The UV-visible absorption spectrum of the aqueous solution of Se nano material.It can be seen that In
Under lower concentration, Ni0.85Se nano material just has higher near infrared absorption, shows that it can be used near infrared light induction
Photo-thermal therapy, photoacoustic imaging.
Embodiment 3, photo-thermal heating test
Take the Ni of various concentration in 3mL embodiment 2 (0~500 μM)0.85The aqueous solution of Se nano material is placed in granularity pond
In, the probe of digital display thermometer is immersed in solution, with 808nm laser with the power illumination 10min of 2W, is recorded in every 10 seconds
The temperature of solution tests various concentration Ni0.85The photo-thermal heating curve of Se nano material, is as a result shown in Fig. 5.As can be seen that
Under 808nm laser irradiation, Ni0.85Se nano material can reach higher temperature under lower concentration, show Ni0.85Se
Nano material can be applied to the photo-thermal therapy of tumour.
Fig. 6 is Ni0.85Se nano material aqueous solution irradiates 5 photo-thermal stablizing effect figures repeatedly under 808nm laser.Tool
Body takes 340 μM of 3mL concentration of Ni0.85The aqueous solution of Se nano material is placed in granularity pond, then with 808nm laser with 2W
Power illumination 10min, then turn off 808nm laser, allow it to naturally cool to initial temperature, use thermometer in the process
Record the variation of temperature, so circulation 5 times.It can be seen that Ni0.85Se nano material has good photo and thermal stability.
Embodiment 4, Ni0.85The living body photoacoustic imaging of Se nano material
Take 100 μ L Ni0.85The aqueous solution (concentration 5M) of Se nano material is by intravenous injection to being inoculated with human cervical cancer 1
The female BAl BIc of tumour/C nude mice (weight 20g) in vivo, and carries out photoacoustic imaging scanning to it after injecting 0h, 4h, with
This injects the front and back variation of mouse tumor image areas and the size of optoacoustic intensity value to observe.
Fig. 7 is that Ni is injected in Mice Body0.85Photoacoustic imaging comparison diagram before and after Se nano material, it can be seen that do not inject
Ni0.85When Se nano material, mouse tumor position can only see very faint photoacoustic signal;And inject Ni0.85Se nanometers of materials
Expect 4h after, mouse tumor locus it can be seen that very strong photoacoustic signal, shows Ni0.85Se nano material can be used as swollen
The contrast agent of the photoacoustic imaging of tumor.
Embodiment 5, Ni0.85The preparation of Se Nano medication compound
By the Ni of 3mg0.85Se nano material and 0.3mg adriamycin are dispersed in 3mL phosphate buffer (pH=7.4),
Then it is placed on magnetic stirring apparatus, is protected from light stirring for 24 hours.10min is centrifuged with the revolving speed of 9000rpm/min again, uses milli-Q water
For several times, unadsorbed Doxorubicin solution is separated to get Ni is arrived0.85It, is dispersed in 3mL phosphoric acid by Se Nano medication compound again
In salt buffer (pH=7.4), it is protected from light at 4 DEG C and saves for use.
Take the Ni of the above-mentioned preparation of 1mL0.85Se Nano medication compound is placed in bag filter, is then individually placed to equipped with 30mL
In the centrifuge tube for the phosphate buffer that pH value is 7.4 and 5.0, then it is placed in 37 DEG C of shaking table.At regular intervals, therefrom
3mL supernatant is taken out, and the phosphate solution of equivalent is added thereto.It is counted by the fluorescent value of adriamycin in measurement supernatant
Calculate the release conditions of different adriamycins.For the ease of comparing, test and 1mL Ni0.85Contained Ah mould in Se Nano medication compound
Drug release situation of the pure Doxorubicin solution of plain equivalent under pH value 7.4.
Fig. 8 is free adriamycin, Ni0.85Se Nano medication compound is in the case where pH is 7.4 and 5.0 phosphate buffer
Drug release patterns, it can be seen that Ni0.85Se Nano medication compound, may be implemented the drug release of pH response, and pH value is got over
It is low, drug release it is more.Show Ni0.85Se can be used as chemotherapy of the pharmaceutical carrier for tumour.
Fig. 9 is mtt assay characterization irradiation front and back free adriamycin, Ni0.85Se nano material and Ni0.85Se Nano medication is compound
Object is to Hela cell activity figure (a is laser irradiation 0min, and b is laser irradiation 5min).
Specific test mode are as follows: by the aqueous solution of free adriamycin, Ni0.85Se nano material aqueous solution and Ni0.85Se nanometers
Medicinal composition is separately added into culture medium, is denoted as culture medium a, b, c respectively.Wherein in culture medium a adriamycin concentration and training
Support Ni in base c0.85The concentration of adriamycin is identical in Se Nano medication compound, Ni in culture medium b0.85The concentration of Se nano material
With Ni in culture medium c0.85Se Nano medication compound Ni0.85The concentration of Se nano material is consistent.Then 808nm laser is used respectively
Irradiate 0min and 5min.
In Fig. 9 a when laser irradiation 0min, dissociate adriamycin and Ni0.85Se Nano medication compound water solution is thin to Hela
The influence of born of the same parents is close, and Ni0.85Se nano material aqueous solution is minimum to Hela impact cell.From Fig. 9 b it is found that with 808nm laser
After 2W power illumination 5min, under comparable sodium, Ni0.85Se Nano medication compound ratio Ni0.85Se nano material, free Ah
The cell killing of mycin is bigger, produces the effect of 1+1 > 2, shows Ni0.85Se Nano medication compound is to photo-thermal-chemotherapy combined
Treatment tumour has good curative effect.
The foregoing is merely exemplary embodiment of the present invention, are not intended to limit the invention, all of the invention
Made any modifications, equivalent replacements, and improvements etc., should all be included in the protection scope of the present invention within spirit and principle.
Claims (7)
1. a kind of Ni0.85Se nano material, it is characterised in that: the Ni0.85The partial size of Se nano material is 2~50nm, described
Ni0.85There is hydrophilic ligand modification on the surface of Se nano material.
2. Ni according to claim 10.85Se nano material, it is characterised in that: the hydrophilic ligand be albumin,
At least one of polyacrylic acid and hyaluronic acid.
3. a kind of Ni of any of claims 1 or 20.85The preparation method of Se nano material, which comprises the steps of:
(1) under inert gas protection, selenium powder and sodium borohydride are dissolved in water, be uniformly mixed, be then restored to solution without
Color obtains sodium hydrogen selenide solution;
(2) mixed aqueous solution of hydrophilic ligand and nickel salt is added drop-wise in the sodium hydrogen selenide solution, is then stirred at room temperature
5min~2h, centrifugation obtain Ni0.85Se nano material;
(3) by the Ni0.85Se nano material, which is placed in ultrapure water, dialyses for 24 hours, changes a water every 3~4h, that is, obtains
Ni0.85The aqueous solution of Se nano material.
4. preparation method according to claim 3, it is characterised in that: the nickel salt be nickel chloride, nickel acetate, nickel nitrate,
At least one of nickelous bromide and nickel iodide.
5. preparation method according to claim 3, it is characterised in that: the ratio between amount of substance of selenium powder and sodium borohydride is 1:
3, the ratio between nickel salt and the amount of substance of selenium powder are 1:1.
6. a kind of Ni of any of claims 1 or 20.85Se nano material is in preparation for loading anticancer drug by suction-operated
Pharmaceutical carrier in application, and/or the application in preparation photo-thermal therapy agent, and/or in the contrast agent for preparing photoacoustic imaging
In application.
7. application according to claim 6, it is characterised in that: the anticancer drug is cis-platinum, adriamycin, camptothecine, soft
At least one of erythromycin, vincaleukoblastinum, tamoxifen and bleomycin.
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