CN109266349A - The preparation method and applications of conversion nano particle on a kind of water-solubility rare-earth - Google Patents
The preparation method and applications of conversion nano particle on a kind of water-solubility rare-earth Download PDFInfo
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- CN109266349A CN109266349A CN201811269813.5A CN201811269813A CN109266349A CN 109266349 A CN109266349 A CN 109266349A CN 201811269813 A CN201811269813 A CN 201811269813A CN 109266349 A CN109266349 A CN 109266349A
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- 239000002105 nanoparticle Substances 0.000 title claims abstract description 133
- 238000006243 chemical reaction Methods 0.000 title claims abstract description 122
- 229910052761 rare earth metal Inorganic materials 0.000 title claims abstract description 84
- 150000002910 rare earth metals Chemical class 0.000 title claims abstract description 47
- 238000002360 preparation method Methods 0.000 title claims abstract description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 238000002595 magnetic resonance imaging Methods 0.000 claims abstract description 8
- 238000000799 fluorescence microscopy Methods 0.000 claims abstract description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 30
- 239000002904 solvent Substances 0.000 claims description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 24
- -1 rare earth oleate Chemical class 0.000 claims description 24
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 claims description 22
- 239000002202 Polyethylene glycol Substances 0.000 claims description 20
- 229920001223 polyethylene glycol Polymers 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 19
- 229910052769 Ytterbium Inorganic materials 0.000 claims description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 14
- 238000009835 boiling Methods 0.000 claims description 14
- 238000010792 warming Methods 0.000 claims description 14
- NAWDYIZEMPQZHO-UHFFFAOYSA-N ytterbium Chemical compound [Yb] NAWDYIZEMPQZHO-UHFFFAOYSA-N 0.000 claims description 12
- 235000013024 sodium fluoride Nutrition 0.000 claims description 11
- 239000011775 sodium fluoride Substances 0.000 claims description 11
- 229910052691 Erbium Inorganic materials 0.000 claims description 10
- 229910052689 Holmium Inorganic materials 0.000 claims description 10
- 229910052775 Thulium Inorganic materials 0.000 claims description 9
- 235000019441 ethanol Nutrition 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- 239000008367 deionised water Substances 0.000 claims description 8
- 229910021641 deionized water Inorganic materials 0.000 claims description 8
- KJZYNXUDTRRSPN-UHFFFAOYSA-N holmium atom Chemical compound [Ho] KJZYNXUDTRRSPN-UHFFFAOYSA-N 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 7
- UYAHIZSMUZPPFV-UHFFFAOYSA-N erbium Chemical compound [Er] UYAHIZSMUZPPFV-UHFFFAOYSA-N 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 229940049964 oleate Drugs 0.000 claims description 7
- 239000002994 raw material Substances 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 229910052688 Gadolinium Inorganic materials 0.000 claims description 5
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 claims description 5
- 239000003208 petroleum Substances 0.000 claims description 5
- FRNOGLGSGLTDKL-UHFFFAOYSA-N thulium atom Chemical compound [Tm] FRNOGLGSGLTDKL-UHFFFAOYSA-N 0.000 claims description 5
- 229910052727 yttrium Inorganic materials 0.000 claims description 5
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 claims description 5
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 238000005119 centrifugation Methods 0.000 claims description 3
- 239000011261 inert gas Substances 0.000 claims description 3
- 230000001376 precipitating effect Effects 0.000 claims description 3
- 238000000108 ultra-filtration Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000002243 precursor Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
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- 238000012986 modification Methods 0.000 abstract description 4
- 238000011017 operating method Methods 0.000 abstract description 3
- 238000000034 method Methods 0.000 description 29
- 239000000463 material Substances 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 229960004756 ethanol Drugs 0.000 description 8
- CAYGPTUERPUBQK-KVVVOXFISA-N gadolinium;(z)-octadec-9-enoic acid Chemical compound [Gd].CCCCCCCC\C=C/CCCCCCCC(O)=O CAYGPTUERPUBQK-KVVVOXFISA-N 0.000 description 7
- 238000002173 high-resolution transmission electron microscopy Methods 0.000 description 7
- 238000003384 imaging method Methods 0.000 description 7
- 230000002776 aggregation Effects 0.000 description 6
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- 230000000694 effects Effects 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- OAXOJAZGUNGBCG-KVVVOXFISA-N (z)-octadec-9-enoic acid;ytterbium Chemical compound [Yb].CCCCCCCC\C=C/CCCCCCCC(O)=O OAXOJAZGUNGBCG-KVVVOXFISA-N 0.000 description 5
- 238000005054 agglomeration Methods 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 5
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- 150000001991 dicarboxylic acids Chemical class 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 238000002189 fluorescence spectrum Methods 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
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- SQTJTENXYVXDLR-KVVVOXFISA-N erbium;(z)-octadec-9-enoic acid Chemical compound [Er].CCCCCCCC\C=C/CCCCCCCC(O)=O SQTJTENXYVXDLR-KVVVOXFISA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 238000001027 hydrothermal synthesis Methods 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 239000002086 nanomaterial Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000009938 salting Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000005979 thermal decomposition reaction Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- IKVSHRQGYANLFM-KVVVOXFISA-N (z)-octadec-9-enoic acid;thulium Chemical compound [Tm].CCCCCCCC\C=C/CCCCCCCC(O)=O IKVSHRQGYANLFM-KVVVOXFISA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 244000154870 Viola adunca Species 0.000 description 1
- 235000005811 Viola adunca Nutrition 0.000 description 1
- 235000013487 Viola odorata Nutrition 0.000 description 1
- 235000002254 Viola papilionacea Nutrition 0.000 description 1
- ATLJOUJUCRBASY-UHFFFAOYSA-N [Tm].[Yb] Chemical compound [Tm].[Yb] ATLJOUJUCRBASY-UHFFFAOYSA-N 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
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- 210000000981 epithelium Anatomy 0.000 description 1
- KWMNWMQPPKKDII-UHFFFAOYSA-N erbium ytterbium Chemical compound [Er].[Yb] KWMNWMQPPKKDII-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- XWFVFZQEDMDSET-UHFFFAOYSA-N gadolinium(3+);trinitrate;hexahydrate Chemical compound O.O.O.O.O.O.[Gd+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XWFVFZQEDMDSET-UHFFFAOYSA-N 0.000 description 1
- LGMLJQFQKXPRGA-VPVMAENOSA-K gadopentetate dimeglumine Chemical compound [Gd+3].CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O LGMLJQFQKXPRGA-VPVMAENOSA-K 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- HHALJHUNPMFVDC-KVVVOXFISA-N holmium;(z)-octadec-9-enoic acid Chemical compound [Ho].CCCCCCCC\C=C/CCCCCCCC(O)=O HHALJHUNPMFVDC-KVVVOXFISA-N 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/08—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
- C09K11/77—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing rare earth metals
- C09K11/7766—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing rare earth metals containing two or more rare earth metals
- C09K11/7772—Halogenides
- C09K11/7773—Halogenides with alkali or alkaline earth metal
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/0002—General or multifunctional contrast agents, e.g. chelated agents
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
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- A61K49/0054—Macromolecular compounds, i.e. oligomers, polymers, dendrimers
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/12—Macromolecular compounds
- A61K49/126—Linear polymers, e.g. dextran, inulin, PEG
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
- A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
- A61K49/1821—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles
- A61K49/1824—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles
- A61K49/1827—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle
- A61K49/1851—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule
- A61K49/1857—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule the organic macromolecular compound being obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. PLGA
- A61K49/186—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule the organic macromolecular compound being obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. PLGA the organic macromolecular compound being polyethyleneglycol [PEG]
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y20/00—Nanooptics, e.g. quantum optics or photonic crystals
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- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
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- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
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Abstract
The present disclosure provides a kind of preparation methods of conversion nano particle on water-solubility rare-earth, carry out bio-compatible sex modification to the surface of nano particle while nano particle formation, can simplify operating procedure, can accelerate production efficiency, reduce production cost；And the rare earth upconversion nano particle being prepared has excellent water solubility and biocompatibility, can not only apply as contrast agent in magnetic resonance imaging, but also can apply in fluorescence imaging.
Description
Technical field
The present invention relates to a kind of preparation method and application of nano particle, conversion nano on specially a kind of water-solubility rare-earth
The preparation method and applications of particle, belong to technical field of inorganic nanometer material
Background technique
In recent years, along with the fast development of nanosecond science and technology, rare earth ion doped up-conversion nano material is because of its brilliance
Optics, magnetic property have important research and application prospect in fields such as bio-imaging, optical dynamic therapies.Rear-earth-doped
Up-conversion luminescence nanomaterial can by low frequency converting photons be high frequency photon, by sensitizer ion in material and shine in
Heart ion, which carries out regulation, may be implemented to convert visible light or high frequency through the near infrared light of window for the light for being located at biological tissue
Near infrared light.Biological tissue is very weak to this wave band light absorption, thus can to avoid the generation of autofluorescence, thus obtain compared with
High fluorescence signal signal-to-noise ratio.Wherein, the NaYF of Gd doping4Nano particle and Yb3+And Er3+、Tm3+Or Ho3+Codope
NaGdF4Nano particle due to Gd presence, with more brilliant T1Magnetic resonance imaging performance, can be realized simultaneously up-conversion fluorescence
Imaging and magnetic resonance imaging.NaYF4Base rare earth upconversion nano particle and NaGdF4The synthesis of base rare earth upconversion nano particle has
A variety of methods can be selected according to different needs.Currently, the preparation method of rare earth upconversion nano particle mainly includes hydro-thermal
Method, solvent-thermal method and thermal decomposition method.However, hydro-thermal method is difficult to control to the partial size and dispersibility of nano particle, solvent-thermal method and
The rare earth upconversion nano particle of thermal decomposition method preparation has hydrophobicity, and further biologic applications are needed this hydrophobicity material
Material is converted into hydrophilic material, and experimentation is relative complex, cumbersome, and efficiency is lower, is unfavorable for practical application.In addition, upper conversion
Nano particle not only needs it to have water solubility in biologic applications, while also requiring it with good biocompatibility.
Currently, there is no a kind of preparation methods of rare earth upconversion nano particle can be realized method and step in the prior art
Simply, yield is big and the rare earth upconversion nano particle that is prepared has excellent water solubility and biocompatibility.
Therefore it provides the simple and convenient process for preparing of conversion nano particle is art technology in a kind of water-soluble biological compatibility
The problem of personnel's urgent need to resolve.
Summary of the invention
In view of this, the present invention provides a kind of preparation method and applications of conversion nano particle on water-solubility rare-earth,
Its method and step is simple, carries out bio-compatible sex modification to the surface of nano particle while nano particle formation；And it makes
Standby obtained rare earth upconversion nano particle has excellent water solubility and biocompatibility, can be applied to magnetic resonance imaging.
To achieve the goals above, the present invention adopts the following technical scheme:
The preparation method of conversion nano particle on a kind of water-solubility rare-earth, which is characterized in that specifically comprise the following steps:
A, rare earth element presoma, biocompatiblity molecules and sodium fluoride are weighed respectively, measure high boiling solvent, it is spare；
B, above-mentioned raw materials are added in reaction vessel and are passed through inert gas shielding, be then warming up to reaction vessel
100-130 DEG C, and 0.5-1h is kept under the conditions of 100-130 DEG C；It is continuously heating to boil under stirring condition and keeps 0.1-
24h；
C, after reaction system is cooled to 15~25 DEG C, solvent washing, centrifugation, drying is added, obtains described water-soluble raw
Conversion nano particle in object compatibility.
The beneficial effect of above-mentioned optimal technical scheme is: method preparation process disclosed by the invention is simple, in nano particle
Bio-compatible sex modification is carried out to the surface of nano particle while formation, simplifies operating procedure, so as to reduce production
Cost；And the rare earth upconversion nano particle with excellent water solubility and biocompatibility is prepared, there is optics/magnetic
The effect of resonance Double-mode imaging.
It preferably, further include step d, specifically:
Conversion nano particle in water-soluble biological compatibility that step c is obtained is dissolved in deionized water, by dialysis or
Centrifugal ultrafiltration is purified, and conversion nano particle solution in water-soluble biological compatibility is obtained；Then water-soluble biological is compatible
Property on conversion nano particle solution by precipitating, wash and to be dried to obtain in water-soluble biological compatibility conversion nano particle dry
Powder.
Preferably, rare earth element presoma described in step a includes gadolinium presoma, ytterbium presoma, erbium presoma, thulium forerunner
Body, holmium presoma or the one such or a variety of mixture of yttrium presoma.
The beneficial effect of above-mentioned optimal technical scheme is: the present invention uses gadolinium presoma, ytterbium presoma, erbium presoma, thulium
Presoma, holmium presoma or yttrium presoma can be prepared as rare earth element presoma comprising gadolinium, ytterbium, erbium, thulium, holmium or yttrium
Conversion nano particle on the water-solubility rare-earth of equal rare earth elements, may be implemented up-conversion luminescence；Wherein NaYF4And NaGdF4It is mesh
The preceding highest host material of up-conversion luminescence efficiency；In addition, by ytterbium presoma, erbium presoma mixture as rare earth element before
Body is driven, conversion nano particle on the double-doped water-solubility rare-earth of ytterbium erbium can be obtained, and ytterbium can as activator as sensitizer, erbium
To improve upper conversion effect；By ytterbium presoma, thulium presoma mixture as rare earth element presoma, it is double that ytterbium thulium can be obtained
Conversion nano particle on the water-solubility rare-earth mixed, and upper conversion effect can be improved as activator as sensitizer, thulium in ytterbium；By
Ytterbium presoma, holmium presoma mixture as rare earth element presoma, can obtain on the holmium double doped water-solubility rare-earth of ytterbium turn
Nano particle is changed, and ytterbium is sensitizer, holmium is activator, and conversion effect can be improved.
Preferably, rare earth element presoma described in step a includes rare earth oleate, rare earth nitrades or rare earth hydrochloric acid
Salt.
Preferably, biocompatiblity molecules described in step a are polyethylene glycol or polyethyleneglycol derivative, the biofacies
The number-average molecular weight of capacitive molecule is 300~50000.
The beneficial effect of above-mentioned optimal technical scheme is: the polyethylene glycol (PEG) and its derivative that the present invention uses are one
Kind water-soluble high-molecular material, has very low interfacial free energy, and Chain Flexibility is good, activity is high in water, so
With good biocompatibility；Also, since there is polyethylene glycol lesser surface can, be easy to be soaked by aqueous medium, so
The adhesive capacity of blood platelet is all fewer on hydrophilic material surface containing PEG structure, thus polyethylene glycol and its derivative are also
Nano particle can be helped to escape the identification and removing of netted epithelial tissue.Discovery is formed same in nano particle between the present invention is accidental
When, polyethylene glycol and its derivative can form thin film in nano grain surface, intergranular mutual aggregation is prevented, so that
Nano-dispersibility, water solubility, the biocompatibility arrived is good.Meanwhile the present invention uses number-average molecular weight for 300~50000
Biocompatiblity molecules are wrapped in nanoparticle surface, can assign water-soluble nano particle, colloidal stability and bio-compatible
Property.
Preferably, high boiling solvent described in step a includes phenylate, benzyl oxide or octadecylene.
Preferably, rare earth element presoma described in step a, biocompatiblity molecules, the molar ratio of sodium fluoride are 1:
0.5-20:2-16；It then is 1mmol:5-40mL addition according to the molal volume of rare earth element presoma and high boiling solvent ratio
High boiling solvent.
Preferably, rare earth oleate used in the step a is prepared by chemical reaction, specifically includes following step
It is rapid:
1. weighing enuatrol and rare-earth salts respectively, deionized water, ethyl alcohol and n-hexane are then measured respectively, it is spare；
It is chemically reacted 2. above-mentioned raw materials are uniformly mixed；
3. after chemical reaction, rare earth oleate can be obtained by separating-purifying to reaction product；
Preferably, 1. middle rare-earth salts includes rare earth nitrades or rare earth hydrochloride to the step.
Preferably, the step 1. in enuatrol, rare-earth salts, deionized water, ethyl alcohol, hexane stoichiometric ratio be
1mmol:2-6mmol:2-20mL:2-20mL:2-40mL.
Preferably, 2. middle reaction temperature is 15-35 DEG C to the step, reaction time 6-24h.
Preferably, speed of agitator is 400-1000r/min in the step b.
Preferably, solvent used in the step c includes ethyl alcohol, ether, acetone, petroleum ether, ethyl acetate or hexane
One of or a variety of mixtures.
The beneficial effect of above-mentioned optimal technical scheme is: inventor chances on the water-soluble nano that the present invention is prepared
Particle does not dissolve in ether, acetone, petroleum ether, ethyl acetate and hexane equal solvent, so the present invention utilizes above-mentioned solvent to wash
Reactant can only be such that high boiling solvent is dissolved in above-mentioned solvent, so as to remove high boiling solvent, to reach purified water
The purpose of dissolubility nanoparticle.
Preferably, the partial size of conversion nano particle is 2-100nm on the water-solubility rare-earth that the step c is prepared.
Conversion nano particle is in magnetic resonance imaging and glimmering on a kind of water-solubility rare-earth that preparation method as described above obtains
Application in light imaging.
The beneficial effect of above-mentioned optimal technical scheme is: conversion nano particle on the water-solubility rare-earth that the present invention is prepared
Not only it can apply as contrast agent in magnetic resonance imaging, but also can apply in fluorescence imaging, there is excellent using effect.
It can be seen via above technical scheme that compared with prior art, the present disclosure provides a kind of water-solubility rare-earths
The preparation method of upper conversion nano particle carries out biocompatibility to the surface of nano particle while nano particle formation and repairs
Decorations, simplified operating procedure can accelerate production efficiency, reduce production cost；And the rare earth upconversion nano being prepared
Particle has excellent water solubility and biocompatibility, can not only apply as contrast agent in magnetic resonance imaging, but also can answer
Used in fluorescence imaging.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described, it should be apparent that, the accompanying drawings in the following description is only this
The embodiment of invention for those of ordinary skill in the art without creative efforts, can also basis
The attached drawing of offer obtains other attached drawings.
Conversion nano particle NaGdF in the 25nm water-soluble biological compatibility that Fig. 1 attached drawing is prepared for embodiment 14:Yb3 +,Er3+Conversion nano particle NaGdF in the 15nm water-soluble biological compatibility that (20/2mol%), embodiment 2 are prepared4:Yb3 +,Er3+Conversion nano particle in the 9nm water-soluble biological compatibility that (30/1.5mol%) and embodiment 3 are prepared
NaGdF4:Yb3+,Er3+The XRD diagram of (30/1mol%)；
Conversion nano particle NaGdF in the 25nm water-soluble biological compatibility that Fig. 2 attached drawing is prepared for embodiment 14:Yb3 +,Er3+The TEM of (20/2mol%) schemes and HR-TEM figure；
Conversion nano particle NaGdF in the 25nm water-soluble biological compatibility that Fig. 3 attached drawing is prepared for embodiment 14:Yb3 +,Er3+The stability analysis of (20/2mol%) in the salting liquid of various concentration；
Conversion nano particle NaGdF in the 25nm water-soluble biological compatibility that Fig. 4 attached drawing is prepared for embodiment 14:Yb3 +,Er3+The T of (20/2mol%)1Weighted imaging figure；
Conversion nano particle NaGdF in the 15nm water-soluble biological compatibility that Fig. 5 attached drawing is prepared for embodiment 24:Yb3 +,Er3+The TEM of (30/1.5mol%) schemes and HR-TEM figure；
Conversion nano particle NaGdF in the 15nm water-soluble biological compatibility that Fig. 6 attached drawing is prepared for embodiment 24:Yb3 +,Er3+The cytotoxicity analysis of (30/1.5mol%)；
Conversion nano particle NaGdF in the 9nm water-soluble biological compatibility that Fig. 7 attached drawing is prepared for embodiment 34:Yb3 +,Er3+The TEM of (30/1mol%) schemes；
Fig. 8 attached drawing is conversion nano particle NaGdF in 25nm water-soluble biological compatibility4:Yb3+,Er3+(20/2mol%),
Conversion nano particle NaGdF in 15nm water-soluble biological compatibility4:Yb3+,Er3+(30/1.5mol%) and 9nm water-soluble biological
Conversion nano particle NaGdF in compatibility4:Yb3+,Er3+The fluorescence spectra of (30/1mol%)；
Conversion nano particle NaGdF in the 30nm water-soluble biological compatibility that Fig. 9 attached drawing is prepared for embodiment 44:Yb3 +,Tm3+The XRD diagram of (20/5mol%)；
Conversion nano particle NaGdF in the 30nm water-soluble biological compatibility that Figure 10 is prepared for embodiment 44:Yb3+,
Tm3+The TEM of (20/5mol%) schemes；
Conversion nano particle NaGdF in the 30nm water-soluble biological compatibility that Figure 11 is prepared for embodiment 44:Yb3+,
Tm3+The fluorescence spectra of (20/5mol%)；
Conversion nano particle NaGdF in the 25nm water-soluble biological compatibility that Figure 12 is prepared for embodiment 54:Yb3+,
Ho3+The XRD diagram of (20/2mol%)；
Conversion nano particle NaGdF in the 25nm water-soluble biological compatibility that Figure 13 is prepared for embodiment 54:Yb3+,
Ho3+The TEM of (20/2mol%) schemes；
Conversion nano particle NaGdF in the 25nm water-soluble biological compatibility that Figure 14 is prepared for embodiment 54:Yb3+,
Ho3+The infrared spectrogram of (20/2mol%)；
Conversion nano particle NaGdF in the 25nm water-soluble biological compatibility that Figure 15 is prepared for embodiment 54:Yb3+,
Ho3+The stability analysis of (20/2mol%).
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts every other
Embodiment shall fall within the protection scope of the present invention.
The embodiment of the invention discloses a kind of preparation methods of conversion nano particle on water-solubility rare-earth, specifically include as follows
Step:
A, rare earth element presoma, biocompatiblity molecules and sodium fluoride are weighed respectively, measure high boiling solvent, it is spare；
B, above-mentioned raw materials are added in reaction vessel and are passed through inert gas shielding, be then warming up to reaction vessel
100-130 DEG C, and 0.5-1h is kept under the conditions of 100-130 DEG C；Then the water in reaction system is removed；Continue under stirring condition
It is warming up to reflux, continues the 0.1-24h that flows back；
C, after reaction system is cooled to 15~25 DEG C, solvent washing, centrifugation, drying is added, obtains the water solubility
Conversion nano particle on biocompatibility；
D, conversion nano particle in water-soluble biological compatibility that step c is obtained is dissolved in deionized water, passes through dialysis
Or centrifugal ultrafiltration is purified, and conversion nano particle solution in water-soluble biological compatibility is obtained；Then by water-soluble biological phase
Conversion nano particle solution is dry by precipitating, washing and being dried to obtain conversion nano particle in water-soluble biological compatibility in capacitive
Powder.
For further optimisation technique scheme, rare earth element presoma includes gadolinium presoma, ytterbium presoma, erbium forerunner
Body, thulium presoma, holmium presoma or yttrium presoma is one such or a variety of mixing.
For further optimisation technique scheme, rare earth element presoma includes rare earth oleate, rare earth nitrades or dilute
Earth salt hydrochlorate.
For further optimisation technique scheme, biocompatiblity molecules are polyethylene glycol or polyethyleneglycol derivative, life
The number-average molecular weight of object biocompatiblity molecules is 300~50000.
For further optimisation technique scheme, high boiling solvent includes phenylate, benzyl oxide or octadecylene.
For further optimisation technique scheme, rare earth element presoma, biocompatiblity molecules, the chemical of sodium fluoride are counted
Amount is then 1mmol:5- according to the molal volume of rare earth element presoma and high boiling solvent ratio than being 1:0.5-20:2-16
High boiling solvent is added in 40mL.
For further optimisation technique scheme, rare earth oleate used in step a is prepared by chemical reaction,
Specifically comprise the following steps:
1. weighing enuatrol and rare-earth salts respectively, deionized water, ethyl alcohol and n-hexane are then measured respectively, it is spare；
It is chemically reacted 2. above-mentioned raw materials are uniformly mixed；
3. after chemical reaction, rare earth oleate can be obtained by separating-purifying to reaction product；
For further optimisation technique scheme, 1. middle rare-earth salts includes rare earth nitrades or rare earth hydrochloride to step.
For further optimisation technique scheme, step 1. in enuatrol, rare-earth salts, deionized water, ethyl alcohol, hexane
Stoichiometric ratio is 1mmol:2-6mmol:2-20mL:2-20mL:2-40mL.
For further optimisation technique scheme, 2. middle reaction temperature is 15-35 DEG C to step, reaction time 6-24h.
For further optimisation technique scheme, the revolving speed stirred in step b is 400-2000rpm.
For further optimisation technique scheme, solvent used in step c include ethyl alcohol, ether, acetone, petroleum ether,
One of ethyl acetate or hexane or a variety of mixing.
For further optimisation technique scheme, the grain of conversion nano particle on the water-solubility rare-earth that step c is prepared
Diameter is 2-100nm.
Embodiment 1
The preparation method of conversion nano particle, specifically comprises the following steps: on a kind of water-solubility rare-earth
A, 19.26g (0.78mmol) oleic acid gadolinium, 2.98g (0.2mmol) oleic acid ytterbium and 0.03g are first weighed respectively
(0.02mmol) oleic acid erbium is added in the dry three-necked flask of 50mL, 20mL octadecylene is then added into flask, then successively
0.34g (4mmol) NaF and 12g (20mmol) polyethylene glycol dicarboxylic acids (M is addedn=600), spare；
B, nitrogen protection is passed through into three-necked flask, warming while stirring keeps 1h to 100 DEG C and under the conditions of 100 DEG C；
Then, continuation is warming up to 310 DEG C under agitation and starts to flow back and react 1h under reflux conditions；
C, after reaction system is cooled to 15~25 DEG C, the mixed solvent of 10mL hexane, 30mL acetone and 3mL ether is added
It is washed and is centrifugated, washed repeatedly, be centrifugated three times, 25nm water-soluble biological phase then can be obtained by drying
Conversion nano particle NaGdF in capacitive4:Yb3+,Er3+(20/2mol%).
Embodiment 2
The preparation method of conversion nano particle, specifically comprises the following steps: on a kind of water-solubility rare-earth
A, 16.92g (0.685mmol) oleic acid gadolinium, 4.47g (0.3mmol) oleic acid ytterbium and 0.02g are first weighed respectively
(0.015mmol) oleic acid erbium is added in the dry three-necked flask of 50mL, and 10mL benzyl oxide is then added into flask, then is successively added
Enter 0.085g (2mmol) NaF and 2.4g (4mmol) polyethylene glycol dicarboxylic acids (Mn=600), spare；
B, nitrogen protection is passed through into three-necked flask, warming while stirring is kept to 105 DEG C and under the conditions of 105 DEG C
0.5h；Then, continuation is warming up to 298 DEG C under agitation and starts to flow back and react 1h under reflux conditions；
C, after reaction system is cooled to 15~25 DEG C, 10mL ethyl acetate is added and is washed and is centrifugated, repeats
Three times, conversion nano particle in 15nm water-soluble biological compatibility then can be obtained by drying in washing, centrifuge separation
NaGdF4:Yb3+,Er3+(30/1.5mol%).
Embodiment 3
The preparation method of conversion nano particle, specifically comprises the following steps: on a kind of water-solubility rare-earth
A, 17.04g (0.69mmol) oleic acid gadolinium, 4.47g (0.3mmol) oleic acid ytterbium and 0.01g are first weighed respectively
(0.01mmol) oleic acid erbium is added in the dry three-necked flask of 50mL, and 35mL phenylate is then added into flask, then is successively added
Enter the single-ended carboxyl polyethylene glycol (M of 1.36g (16mmol) NaF and 1.2g (2mmol)n=600), spare；
B, nitrogen protection is passed through into three-necked flask, warming while stirring is kept to 130 DEG C and under the conditions of 130 DEG C
0.5h；Then, continuation is warming up to 260 DEG C under agitation and starts to flow back and react 0.5h under reflux conditions；
C, after reaction system is cooled to 15~25 DEG C, addition is washed and is centrifugated with 10mL petroleum ether, is repeated
Three times, conversion nano particle in 9nm water-soluble biological compatibility then can be obtained by drying in washing, centrifuge separation
NaGdF4:Yb3+,Er3+(30/1mol%).
Embodiment 4
The preparation method of conversion nano particle, specifically comprises the following steps: on a kind of water-solubility rare-earth
A, 18.52g (0.75mmol) oleic acid gadolinium, 2.98g (0.2mmol) oleic acid ytterbium and 0.06g are first weighed respectively
(0.05mmol) oleic acid thulium is added in the dry three-necked flask of 50mL, 20mL octadecylene is then added into flask, then successively
0.34g (4mmol) NaF and 9.2g (2mmol) polyethylene glycol dicarboxylic acids (M is addedn=4600), spare；
B, nitrogen protection is passed through into three-necked flask, warming while stirring keeps 1h to 135 DEG C and under the conditions of 135 DEG C；
Then, continuation is warming up to 310 DEG C under agitation and starts to flow back and react 10h under reflux conditions；
C, after reaction system is cooled to 15~25 DEG C, the mixing of 10mL ethyl alcohol, 30mL acetone and 3mL ether composition is added
Solvent is washed and is centrifugated, and is washed repeatedly, is centrifugated three times, and the life of 30nm water solubility then can be obtained by dry
Conversion nano particle NaGdF in object compatibility4:Yb3+,Tm3+(20/5mol%).
Embodiment 5
The preparation method of conversion nano particle, specifically comprises the following steps: on a kind of water-solubility rare-earth
A, 18.52g (0.75mmol) oleic acid gadolinium, 2.98g (0.2mmol) oleic acid ytterbium and 0.06g are first weighed respectively
(0.05mmol) oleic acid holmium is added in the dry three-necked flask of 50mL, 20mL octadecylene is then added into flask, then successively
0.34g (4mmol) NaF and 6g (10mmol) polyethylene glycol (M is addedn=600), spare；
B, nitrogen protection is passed through into three-necked flask, warming while stirring keeps 1h to 100 DEG C and under the conditions of 100 DEG C；
Then, continuation is warming up to 310 DEG C under agitation and starts to flow back and react 1h under reflux conditions；
C, after reaction system is cooled to 15~25 DEG C, the mixed solvent of 10mL hexane, 30mL acetone and 3mL ether is added
It is washed and is centrifugated, washed repeatedly, be centrifugated three times, 25nm water-soluble biological phase then can be obtained by drying
Conversion nano particle NaGdF in capacitive4:Yb3+,Ho3+(20/2mol%).
Embodiment 6
Oleic acid gadolinium presoma is prepared with the following method in Examples 1 to 5, specifically comprises the following steps:
1. weighing 1mmol gadolinium nitrate hexahydrate (Gd (NO respectively3)3·6H2) and 3mmol enuatrol (C O17H33COONa),
Then 3mL deionized water, 4mL dehydrated alcohol and 7mL n-hexane are measured respectively, it is spare；
2. adjustment, is persistently stirred at room temperature.Above-mentioned raw materials are uniformly mixed under the magnetic agitation of 600rpm, and are continued
12h is reacted under room temperature, stirring condition；
3. after chemical reaction, removing water layer using separatory funnel, organic layer 10mL distilled water and ethyl alcohol being mixed
Liquid (V/V=1:1) washs three times, removes solvent and obtains oleic acid gadolinium presoma.
The upper conversion nano particle that above-described embodiment 1-5 is prepared is characterized.
1, conversion nano particle NaGdF in the 25nm water-soluble biological compatibility that embodiment 1 is prepared4:Yb3+,Er3+
Conversion nano particle NaGdF in the 15nm water-soluble biological compatibility that (20/2mol%), embodiment 2 are prepared4:Yb3+,Er3+
Conversion nano particle NaGdF in the 9nm water-soluble biological compatibility that (30/1.5mol%) and embodiment 3 are prepared4:Yb3 +,Er3+(30/1mol%) carries out X-ray diffraction, as a result as shown in Figure 1.
Fig. 1 is as the result is shown: the XRD diagram and NaGdF for the product that embodiment 1, embodiment 2 and embodiment 3 are prepared4Standard
Card (JCPDS No.27-0699) correspond, and peak intensity and its between ratio it is also unanimous on the whole with standard card, say
Bright host material NaGdF4Success synthesizes, and crystal growth is good, is hexagonal phase crystal form, illustrates Yb, Er doping to main structure
It has not significant impact.In addition, the position of diffraction maximum is compared with the position of standard card superiors, it is whole to be deviated to wide-angle, due to
Yb and Er ionic radius ratio Gd ion is small, further shows that Yb, Er are successfully doped into NaGdF according to bragg's formula4Base
In matter.
2, conversion nano particle NaGdF in the 25nm water-soluble biological compatibility that embodiment 1 is prepared4:Yb3+,Er3+
(20/2mol%) shoots photo under transmission electron microscope (TEM) and high resolution TEM (HR-TEM), as a result as shown in Figure 2.
Fig. 2 is as the result is shown: the average grain diameter of nano particle is 25nm, and nano particle does not have apparent agglomeration, shows
Nano particle favorable dispersibility in water.Spacing of lattice is corresponding (101) face 0.297nm in HR-TEM figure, shows NaGdF4:
Yb3+,Er3+(20/2mol%) nano particle crystalline state is good.
3, conversion nano particle NaGdF in the 25nm water-soluble biological compatibility that embodiment 1 is prepared4:Yb3+,Er3+
(20/2mol%) is placed in different concentration in the NaCl salting liquid of 0.08-2.5mmol/L, and measures its hydrated diameter, as a result
As shown in Figure 3.
Fig. 3 is as the result is shown: the hydrated diameter of nano particle does not have significant changes, shows nano particle in 0.08-
Without significantly reunion behavior in the NaCl solution of 2.5mmol/L, there is good colloidal stability.
4, conversion nano particle NaGdF in the 25nm water-soluble biological compatibility that embodiment 1 is prepared4:Yb3+,Er3+
(20/2mol%) carries out T1Weighted imaging, as a result as shown in Figure 4.
Fig. 4 is as the result is shown: as the concentration of nano particle increases, T1Weighted imaging gradually brightens, and pcolor gradually reddens,
External imaging changing rule is obvious, and the r of nano particle1Value is 4.6956mM-1s-1, it is greater than clinical contrast agent Magnevist.
5, conversion nano particle NaGdF in the 15nm water-soluble biological compatibility that embodiment 2 is prepared4:Yb3+,Er3+
(30/1.5mol%) shoots photo under transmission electron microscope (TEM) and high resolution TEM (HR-TEM), as a result such as Fig. 5 institute
Show.
Shown in Fig. 5 result: nano particle does not have apparent agglomeration, average grain diameter 15nm, nano particle crystalloid
State is good.
6, conversion nano particle NaGdF in the 15nm water-soluble biological compatibility that embodiment 2 is prepared4:Yb3+,Er3+
Cytotoxicity under (30/1.5mol%) various concentration is detected, as a result as shown in Figure 6.
Fig. 6 is as the result is shown: the survival rate of HeLa cell is still maintained at 90% under the conditions of high concentration (100mg/L Gd)
More than, display nano particle freeze-dried powder does not have significant cytotoxicity, shows the upper conversion nano being prepared using this method
Particle has good biocompatibility.
7, conversion nano particle NaGdF in the 9nm water-soluble biological compatibility that embodiment 3 is prepared4:Yb3+,Er3+
(30/1mol%) shoots photo at transmission electron microscope (TEM), as a result as shown in Figure 7.
Fig. 7 is as the result is shown: nano particle does not have apparent agglomeration, average grain diameter 9nm, nano particle crystalline state
Well.
8, to conversion nano particle NaGdF in 25nm water-soluble biological compatibility4:Yb3+,Er3+(20/2mol%), 15nm
Conversion nano particle NaGdF in water-soluble biological compatibility4:Yb3+,Er3+(30/1.5mol%) and 9nm water-soluble biological are compatible
Conversion nano particle NaGdF in property4:Yb3+,Er3+(30/1mol%) carries out fluorescence spectrum detection, as a result as shown in Figure 8.
Fig. 8 is as the result is shown: having strong emission peak at about 526nm, is due to Er3+'s2H11/2→4I15/2、4S3/2→4I15/2
Transition, corresponding green emission.The result shows that by change reactant in rare earth precursor ratio, can regulate and control Yb in matrix,
The ratio of Er doping, so as to adjust the launch wavelength and luminous intensity of nano particle.
9, conversion nano particle NaGdF in the 30nm water-soluble biological compatibility that embodiment 4 is prepared4:Yb3+,Tm3+
(20/5mol%) carries out X-ray diffraction, as a result as shown in Figure 9；
Fig. 9 is as the result is shown: with NaGdF4The quantity at peak and distribution etc. are corresponding in standard card (JCPDS No.27-0699),
Illustrate host material NaGdF4Growing state is good, and is hexagonal phase crystal form.In addition, in the position and standard card of diffraction maximum
Peak position is compared, whole to deviate to wide-angle, since Yb and Tm ionic radius ratio Gd ion is small, according to bragg's formula, into one
Step shows that Yb, Tm are successfully doped into NaGdF4In matrix.
10, conversion nano particle NaGdF in the 30nm water-soluble biological compatibility that Figure 10 is prepared for embodiment 44:Yb3 +,Tm3+(20/5mol%) shoots photo at transmission electron microscope (TEM), and the results are shown in Figure 10.
Figure 10 is not the results show that nano particle has apparent agglomeration, average grain diameter 30nm.
11, conversion nano particle NaGdF in the 30nm water-soluble biological compatibility that embodiment 4 is prepared4:Yb3+,
Tm3+(20/5mol%) carries out fluorescence spectrum detection；
Figure 11 is respectively corresponded the results show that the emission peak at 474nm is better than the peak of 696nm1D2→3F4Transition process with1G4
→3H6Transition process.In addition, sample issues apparent blue violet light after 980nm excitation, this is because1D2→3F4Transition process hair
Purple light out with1G4→3H6The result that the blue light that transition process issues generates after being overlapped.
12, conversion nano particle NaGdF in the 25nm water-soluble biological compatibility that embodiment 5 is prepared4:Yb3+,
Ho3+The carry out X-ray diffraction test of (20/2mol%), as a result as shown in figure 12.
Figure 12 is as the result is shown: the XRD diagram and NaGdF for the product that embodiment 5 is prepared4Standard card (JCPDS
No.27-0699 the quantity at peak and distribution etc. are corresponding in), illustrate host material NaGdF4Growing state is good, is that hexagonal phase is brilliant
Type.The position of diffraction maximum is whole to deviate to wide-angle compared with the peak position in standard card, this is because Yb and Ho ion half
Diameter ratio Gd ionic radius is small, according to bragg's formula, further demonstrates that Yb, Ho are successfully doped into NaGdF4In matrix.
13, conversion nano particle NaGdF in the 25nm water-soluble biological compatibility that embodiment 5 is prepared4:Yb3+,
Ho3+(20/2mol%) shoots photo at transmission electron microscope (TEM), as a result as shown in figure 13.
Figure 13 is not the results show that nano particle has apparent agglomeration, average grain diameter 25nm.
14, conversion nano particle NaGdF in the 25nm water-soluble biological compatibility that embodiment 5 is prepared4:Yb3+,
Ho3+(20/2mol%) carries out infrared spectroscopy detection, as a result as shown in figure 14；
Figure 14 is as the result is shown: wherein 3400cm-1Place be in polyethylene glycol dicarboxylic acids in-OH characteristic absorption peak, 2922cm-1And 2873cm-1Place is the stretching vibration of alkyl C-H, 1110cm-1Place is the absorption peak of the C-O-C of polyethylene glycol dicarboxylic acids,
1740cm-1And 908cm-1The absorption peak at place shows that nano grain surface is successfully repaired from the characteristic absorption peak of-COO- group
Polyethylene glycol is adornd, and surface has carboxyl functional group.
15, conversion nano particle NaGdF in the 25nm water-soluble biological compatibility that embodiment 5 is prepared4:Yb3+,
Ho3+The stability of (20/2mol%) is detected, as a result as shown in figure 15
Figure 15 is as the result is shown: showing the narrow distribution of nano particle, without significantly reunion behavior, has good glue
Body stability.
Each embodiment in this specification is described in a progressive manner, the highlights of each of the examples are with other
The difference of embodiment, the same or similar parts in each embodiment may refer to each other.For device disclosed in embodiment
For, since it is corresponded to the methods disclosed in the examples, so being described relatively simple, related place is said referring to method part
It is bright.
The foregoing description of the disclosed embodiments enables those skilled in the art to implement or use the present invention.
Various modifications to these embodiments will be readily apparent to those skilled in the art, as defined herein
General Principle can be realized in other embodiments without departing from the spirit or scope of the present invention.Therefore, of the invention
It is not intended to be limited to the embodiments shown herein, and is to fit to and the principles and novel features disclosed herein phase one
The widest scope of cause.
Claims (10)
1. the preparation method of conversion nano particle on a kind of water-solubility rare-earth, which is characterized in that specifically comprise the following steps:
A, rare earth element presoma, biocompatiblity molecules and sodium fluoride are weighed respectively, measure high boiling solvent, it is spare；
B, above-mentioned raw materials are added in reaction vessel and are passed through inert gas shielding, reaction vessel is then warming up to 100-
130 DEG C, and 0.5-1h is kept under the conditions of 100-130 DEG C；It is continuously heating to boil under stirring condition and keeps 0.1-24h；
C, after reaction system is cooled to 15~25 DEG C, washed solvent, centrifugation, drying is added, obtains the water-soluble biological
Conversion nano particle in compatibility.
2. the preparation method of conversion nano particle on a kind of water-solubility rare-earth according to claim 1, which is characterized in that also
Including step d, specifically:
Conversion nano particle in water-soluble biological compatibility that step c is obtained is dissolved in deionized water, by dialysing or being centrifuged
Ultrafiltration is purified, and conversion nano particle solution in water-soluble biological compatibility is obtained；It then will be in water-soluble biological compatibility
Conversion nano particle solution is by precipitating, washing and be dried to obtain conversion nano particle dry powder in water-soluble biological compatibility.
3. the preparation method of conversion nano particle on a kind of water-solubility rare-earth according to claim 1, which is characterized in that step
Before rare earth element presoma described in rapid a includes gadolinium presoma, ytterbium presoma, erbium presoma, thulium presoma, holmium presoma or yttrium
Drive the one such or a variety of mixture of body.
4. the preparation method of conversion nano particle on a kind of water-solubility rare-earth according to claim 1, which is characterized in that step
Rare earth element presoma described in rapid a includes rare earth oleate, rare earth nitrades or rare earth hydrochloride.
5. the preparation method of conversion nano particle on a kind of water-solubility rare-earth according to claim 1, which is characterized in that step
Biocompatiblity molecules described in rapid a are polyethylene glycol or polyethyleneglycol derivative, and the number of the biocompatiblity molecules is divided equally
Son amount is 300~50000.
6. the preparation method of conversion nano particle on a kind of water-solubility rare-earth according to claim 1, which is characterized in that step
High boiling solvent described in rapid a includes phenylate, benzyl oxide or octadecylene.
7. the preparation method of conversion nano particle on a kind of water-solubility rare-earth according to claim 1, which is characterized in that step
Rare earth element presoma described in rapid a, biocompatiblity molecules, the molar ratio of sodium fluoride are 1:0.5-20:2-16；According to rare earth
The molal volume of elemental precursor and high boiling solvent ratio is that high boiling solvent is added in 1mmol:5-40mL.
8. the preparation method of conversion nano particle on a kind of water-solubility rare-earth according to claim 1, which is characterized in that institute
Stating speed of agitator in step b is 400-1000r/min.
9. the preparation method of conversion nano particle on a kind of water-solubility rare-earth according to claim 1, which is characterized in that institute
It includes one of ethyl alcohol, ether, acetone, petroleum ether, ethyl acetate or hexane or a variety of mixed for stating solvent used in step c
It closes.
10. conversion nano on the water-solubility rare-earth that preparation method described in -9 any one is prepared according to claim 1
Application of the grain in magnetic resonance imaging and fluorescence imaging.
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| CN103623436A (en) * | 2012-08-22 | 2014-03-12 | 北京万德高科技发展有限公司 | Magnetic rare earth nanoparticle with biocompatibility, preparation method thereof, and applications of magnetic rare earth nanoparticle in magnetic resonance imaging |
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| JIYOUNG RYU ET AL.: "Facile Synthesis of Ultrasmall and Hexagonal NaGdF4:Yb3+,Er3+ Nanoparticles with Magnetic and Upconversion Imaging Properties", 《J. PHYS. CHEM. C》 * |
| 宣琎楠等: "PEG修饰NaGdF4:Yb3+,Er3+纳米粒子合成及上转换发光性质", 《人工晶体学报》 * |
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| CN113429972A (en) * | 2021-06-25 | 2021-09-24 | 中国农业科学院农业质量标准与检测技术研究所 | Parathion fluorescent probe, preparation method thereof and parathion fluorescent resonance energy transfer detection method based on bionic recognition |
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