CN112704745A - NaErF4@NaGdF4Application of core-shell nanoparticles in preparation of multi-modal contrast agent - Google Patents
NaErF4@NaGdF4Application of core-shell nanoparticles in preparation of multi-modal contrast agent Download PDFInfo
- Publication number
- CN112704745A CN112704745A CN202110025832.9A CN202110025832A CN112704745A CN 112704745 A CN112704745 A CN 112704745A CN 202110025832 A CN202110025832 A CN 202110025832A CN 112704745 A CN112704745 A CN 112704745A
- Authority
- CN
- China
- Prior art keywords
- solution
- naerf
- core
- nagdf
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 80
- 239000011258 core-shell material Substances 0.000 title claims abstract description 50
- 229910021266 NaErF4 Inorganic materials 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 37
- 239000002872 contrast media Substances 0.000 title claims abstract description 24
- 238000003384 imaging method Methods 0.000 claims abstract description 20
- 238000012986 modification Methods 0.000 claims abstract description 10
- 230000004048 modification Effects 0.000 claims abstract description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 63
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 46
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 45
- 238000006243 chemical reaction Methods 0.000 claims description 41
- 238000010438 heat treatment Methods 0.000 claims description 40
- 238000003756 stirring Methods 0.000 claims description 40
- CCCMONHAUSKTEQ-UHFFFAOYSA-N octadec-1-ene Chemical compound CCCCCCCCCCCCCCCCC=C CCCMONHAUSKTEQ-UHFFFAOYSA-N 0.000 claims description 36
- 239000000843 powder Substances 0.000 claims description 28
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 20
- 238000001816 cooling Methods 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 20
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 18
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 18
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 18
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 18
- 239000005642 Oleic acid Substances 0.000 claims description 18
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 18
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- 238000005406 washing Methods 0.000 claims description 11
- 229910052786 argon Inorganic materials 0.000 claims description 10
- 239000012300 argon atmosphere Substances 0.000 claims description 10
- 239000008367 deionised water Substances 0.000 claims description 10
- 229910021641 deionized water Inorganic materials 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 9
- UJBPGOAZQSYXNT-UHFFFAOYSA-K trichloroerbium;hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Cl-].[Er+3] UJBPGOAZQSYXNT-UHFFFAOYSA-K 0.000 claims description 8
- PNYPSKHTTCTAMD-UHFFFAOYSA-K trichlorogadolinium;hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Cl-].[Gd+3] PNYPSKHTTCTAMD-UHFFFAOYSA-K 0.000 claims description 8
- 238000004140 cleaning Methods 0.000 claims description 6
- 238000001556 precipitation Methods 0.000 claims description 5
- 238000003860 storage Methods 0.000 claims description 5
- 238000004020 luminiscence type Methods 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 239000002245 particle Substances 0.000 abstract description 5
- 239000000243 solution Substances 0.000 description 105
- 238000002591 computed tomography Methods 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- 239000007789 gas Substances 0.000 description 12
- 238000002595 magnetic resonance imaging Methods 0.000 description 11
- 238000012360 testing method Methods 0.000 description 8
- 239000012535 impurity Substances 0.000 description 6
- 229910052761 rare earth metal Inorganic materials 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 238000012634 optical imaging Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- -1 rare earth ions Chemical class 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 238000012984 biological imaging Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000000634 powder X-ray diffraction Methods 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 238000003917 TEM image Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000002296 dynamic light scattering Methods 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 238000002189 fluorescence spectrum Methods 0.000 description 2
- 238000010603 microCT Methods 0.000 description 2
- 150000002910 rare earth metals Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000012285 ultrasound imaging Methods 0.000 description 2
- QIVUCLWGARAQIO-OLIXTKCUSA-N (3s)-n-[(3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl]-2-oxospiro[1h-pyrrolo[2,3-b]pyridine-3,6'-5,7-dihydrocyclopenta[b]pyridine]-3'-carboxamide Chemical class C1([C@H]2[C@H](N(C(=O)[C@@H](NC(=O)C=3C=C4C[C@]5(CC4=NC=3)C3=CC=CN=C3NC5=O)C2)CC(F)(F)F)C)=C(F)C=CC(F)=C1F QIVUCLWGARAQIO-OLIXTKCUSA-N 0.000 description 1
- DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 description 1
- 229910052691 Erbium Inorganic materials 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000005415 bioluminescence Methods 0.000 description 1
- 230000029918 bioluminescence Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- UYAHIZSMUZPPFV-UHFFFAOYSA-N erbium Chemical compound [Er] UYAHIZSMUZPPFV-UHFFFAOYSA-N 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 230000005865 ionizing radiation Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000002715 modification method Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000008832 photodamage Effects 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 125000006853 reporter group Chemical group 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
Images
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
- A61K49/0089—Particulate, powder, adsorbate, bead, sphere
- A61K49/0091—Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer
- A61K49/0093—Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—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
- A61K49/1878—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 the nanoparticle having a magnetically inert core and a (super)(para)magnetic coating
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Nanotechnology (AREA)
- Radiology & Medical Imaging (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The invention belongs to the technical field of biomedical imaging, and discloses a NaErF4@NaGdF4The application of the core-shell nano-particles in preparing a multi-modal contrast agent. The preparation method of the contrast agent comprises NaErF4Preparation of bare core nanoparticles, NaErF4@NaGdF4Preparation of core-shell nanoparticles, NaErF4@NaGdF4Three steps of water-solubility modification of core-shell structure nano particles to obtain NaErF4@NaGdF4The nano particles have single appearance and controllable particle size, show excellent developing performance in MRI/CT/UCL representation, and have wide application in the biomedical field.
Description
Technical Field
The invention belongs to the technical field of contrast agents, and particularly relates to NaErF4@NaGdF4The application of the core-shell nano-particles in preparing a multi-modal contrast agent.
Background
Commonly used biological imaging techniques include Optical Imaging (OI), Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), single electron emission computed tomography (SPECT), ultrasound imaging (US), X-ray Computed Tomography (CT), and the like. Among them, MRI, CT and OI imaging have their own characteristics and advantages and disadvantages due to the differences in the imaging principles. MRI is to collect the proton relaxation time information in magnetic field, to avoid the non-ionizing radiation damage in principle; CT is a high-resolution three-dimensional tissue organ anatomy image obtained by acquiring attenuation information of X-rays after penetrating different tissues and analyzing the attenuation information by a computer; however, both the CT and MRI imaging techniques have their own limitations in use, such as insufficient sensitivity to the resolution of the cells, for which the optical imaging happens to be perfectly solved.
Depending on the detection mode, the bio-optical imaging can be classified into fluorescence imaging, bioluminescence imaging, photoacoustic imaging, optical tomography, etc., wherein the fluorescence technology has been widely used in some molecular biology and small molecule in vivo metabolism research. The fluorescence technology can adopt inorganic materials and organic materials as fluorescence reporter groups, wherein the up-conversion mainly depends on doped rare earth ions. Actually, the rare earth doped up-conversion luminescent nanoparticles can convert infrared light into a novel luminescent material of ultraviolet light or visible light, and because the infrared light has the advantages of deep penetration of biological tissues, small light damage, no excitation of autofluorescence and the like, the rare earth doped up-conversion luminescent nanoparticles have great application prospects in the aspects of biological labeling, biological imaging, photodynamic therapy and the like.
In order to make up for the deficiency of a single imaging mode, in actual biological detection, a plurality of biological imaging technologies are often combined to realize comprehensive monitoring of diseases, and development of contrast agents supporting multi-modal imaging is necessary. The invention designs a NaErF4@NaGdF4Gd is introduced when the shell is coated by the core-shell structure nano-particles, so that possibility is provided for MRI imaging; as the Er has proper K-edge binding energy, the contrast efficiency of the CT is effectively enhanced; and secondly, Er has rich energy level and unique 4f electronic structure, is an ideal object for researching the phenomenon of up-conversion luminescence (UCL) and is also a suitable fluorescence sensitizer. NaErF designed based on the invention4@NaGdF4The imaging probe of the core-shell structure nano particles can be simultaneously used for UCL, MRI and CT three-mode imaging.
Disclosure of Invention
Aiming at overcoming the defects and actual needs in the prior art, the invention aims to provide a contrast agent capable of being used for multi-mode imaging, and the core-shell structure NaErF designed by the invention4@NaGdF4The nano-particles have excellent MRI/CT/UCL imaging performance.
In order to realize the purpose, the invention adopts the following technical scheme:
NaErF4@NaGdF4Use of core-shell nanoparticles for the preparation of a multimodal contrast agent for simultaneous MRI, CT and up-conversion luminescence imaging; the preparation of the multi-modal contrast agent comprises NaErF4@NaGdF4Preparing core-shell nano particles and modifying water solubility;
the NaErF4@NaGdF4The preparation of the core-shell nano-particles comprises the following steps:
(1) sequentially adding oleic acid, 1-octadecene and gadolinium chloride hexahydrate into a reaction bottle under the condition of argon atmosphere and continuous stirring, and continuously stirring for 0.5-2h at room temperature after the addition is finished;
(2) heating the solution obtained in the step (1) to 120-180 ℃, stirring for 0.5-2h, and then cooling to room temperature;
(3) mixing NaOH powder and NH4Adding the powder F into a methanol solution, uniformly dispersing by ultrasonic, adding the obtained solution into the reaction solution obtained in the step (2), heating to 50-90 ℃, and keeping for 0.1-2 h;
(4) dropwise adding the solution I prepared in advance into the solution obtained in the step (3), heating to 50-90 ℃, and keeping for 0.5-2 h;
(5) introducing argon into the solution obtained in the step (4), heating to 200-350 ℃, keeping the temperature for 0.5-2h, and then cooling the solution to room temperature;
(6) adding acetone into the solution obtained in the step (5), centrifuging and cleaning to obtain the NaErF4@NaGdF4Core-shell nanoparticles dispersed into ringsObtaining a solution II in a hexane solvent for later use;
the water-soluble modification steps are as follows: and (4) mixing the solution II obtained in the step (6) with a hydrochloric acid solution, stirring, adding acetone for precipitation, centrifuging, washing to obtain ligand-free up-conversion nanoparticles, and dispersing the ligand-free up-conversion nanoparticles into deionized water for storage.
Further, the preparation method of the solution I is as follows:
(1) sequentially adding oleic acid, 1-octadecene and erbium chloride hexahydrate into a reaction bottle under the condition of argon atmosphere and continuous stirring, and continuously stirring for 0.5-2 hours at room temperature after the addition is finished;
(2) heating the solution obtained in the step (1) to 120-180 ℃ at the heating rate of 10-15 ℃/min, stirring for 0.5-2h, and then cooling to room temperature;
(3) mixing NaOH powder and NH4Adding the powder F into a methanol solvent, uniformly dispersing by ultrasonic, adding the obtained solution into the reaction solution obtained in the step (2), heating to 50-90 ℃, and keeping for 0.1-2 h;
(4) introducing argon into the solution obtained in the step (3), heating to 200-350 ℃, stirring for 0.5-2h, and then cooling the solution to room temperature;
(5) adding acetone into the solution obtained in the step (4), centrifuging and cleaning to obtain the NaErF4And (3) dispersing the bare-core nano particles into a cyclohexane solvent to obtain a solution I for later use.
Further, NaErF4@NaGdF4In the preparation of the core-shell nano-particles, the dosage of gadolinium chloride hexahydrate is 200-500mg, the dosage of oleic acid is 5-10mL, the dosage of 1-octadecene is 10-25mL, the dosage of NaOH powder is 25-200mg, and NH is added4The dosage of the F powder is 20-200mg, the dosage of the methanol is 5-20mL, the dosage of the acetone is 10-30mL, and the dosage of the cyclohexane in the solution II is 2-10 mL.
Further, NaErF4@NaGdF4The addition amount of the solution I in the preparation of the core-shell nano-particles is 1-5 mL.
Further, NaErF4@NaGdF4In the preparation of the core-shell nano-particles, the centrifugal rotating speed is 6500-8000 rpm, and the centrifugal time is 4-10 min.
Further, in the preparation of the solution I, the dosage of erbium chloride hexahydrate is 200-500mg, the dosage of oleic acid is 5-10mL, the dosage of 1-octadecene is 10-25mL, the dosage of NaOH powder is 50-200mg, and NH is added4The dosage of the F powder is 100-300mg, the dosage of the methanol is 5-20mL, and the dosage of the acetone is 10-30 mL.
Further, the solvent used in the cleaning process is a solvent with a volume ratio of 1:3, cyclohexane and ethanol.
Further, in the preparation of the solution I, the centrifugal rotation speed is 6000-.
Further, the water-soluble modification has the centrifugation rotating speed of 10000-11000 r/min, the centrifugation time of 10-60min, the addition of acetone of 5-20mL and the pH value of hydrochloric acid solution of 3-5.
Compared with the prior art, the invention has the following beneficial effects:
(1) the NaErF prepared by the preparation method provided by the invention4@NaGdF4The particles have better appearance, and the inventor creatively discovers that the prepared NaErF has better appearance4@NaGdF4The nano-particles have UCL, MRI and CT three-mode imaging capability and have potential application in the field of biomedicine.
(2) The invention searches for the growth dynamics rule of the nano particles by controlling a series of synthesis conditions, such as reaction temperature, reaction time, solute and solvent ratio, and the like, and prepares the product with controllable particle size and uniform appearance.
(3) No report is found on the core-shell nanoparticles based on erbium element as core and gadolinium element as shell, and the method aims at NaErF4@NaGdF4The application of nanoparticles in multi-modal imaging has not been studied yet, and therefore, the application of nanoparticles in UCL, MRI and CT three-mode imaging is proposed for the first time by the applicant.
(4) The present invention is directed to NaErF4@NaGdF4The characteristic optimization modification method of the core-shell nano-particles does not adopt a conventionally used PEG solvent but adopts acetone, so that NaErF is guaranteed4@NaGdF4Core-shell structure nanoThe rice grains are converted from hydrophobicity to hydrophilicity, thus ensuring the basic condition of biological application.
Drawings
FIG. 1 shows NaErF in example 24@NaGdF4TEM images of the nanoparticles;
FIG. 2 shows NaErF in example 24@NaGdF4The particle size distribution of the nanoparticles;
FIG. 3 shows NaErF in example 24@NaGdF4XRD pattern of nanoparticles;
FIG. 4 shows NaErF in example 44@NaGdF4Testing of MRI properties of the nanoparticles;
FIG. 5 shows NaErF in example 54@NaGdF4Testing the CT property of the nano-particles;
FIG. 6 shows NaErF in example 64@NaGdF4And (3) testing the upconversion fluorescence property of the nanoparticles.
The specific implementation mode is as follows:
the invention is further illustrated by the following specific examples. It should be understood that these examples are only for illustrating the present invention and are not intended to limit the scope of the claims of the present invention. Further, it should be understood that various changes and modifications of the present invention may be made by those skilled in the art after reading the teachings of the present invention, and such equivalents may fall within the scope of the present invention as defined in the appended claims.
Erbium chloride hexahydrate (99.9%), gadolinium chloride hexahydrate (99.9%), oleic acid, 1-octadecene, ammonium fluoride, sodium hydroxide, methanol, hydrochloric acid, acetone, absolute ethanol and cyclohexane used in the application are all of analytical grade and purchased from the national drug group, and the water used is deionized water.
Example 1
A multi-mode core-shell nano contrast medium is prepared from NaErF4@NaGdF4Preparing core-shell nano particles and modifying water solubility;
NaErF4@NaGdF4the preparation of the core-shell nano-particles comprises the following steps:
(1) under the condition of argon atmosphere and continuous stirring, sequentially adding 6mL of oleic acid, 15mL of 1-octadecene and 0.25mmol of gadolinium chloride hexahydrate into a reaction bottle, and continuously stirring for 0.5h at room temperature after the addition is finished;
(2) heating the solution obtained in the step (1) to 150 ℃, stirring for 0.5h, and then cooling to room temperature;
(3) 25mg of NaOH powder and 37mg of NH4Adding the powder F into 2.5mL of methanol solution, uniformly dispersing by ultrasonic, adding the obtained solution into the reaction solution obtained in the step (2), heating to 70 ℃, and keeping for 1h until the methanol in the solution is completely removed;
(4) dropwise adding 2mL of solution I prepared in advance into the solution obtained in the step (3), heating to 80 ℃, and keeping for 0.5h until cyclohexane in the solution is completely removed;
(5) introducing argon gas into the solution obtained in the step (4) for 1.0h to remove impurity gas and water vapor, then heating to 300 ℃, keeping for 1.0h, and then naturally cooling the solution to room temperature;
(6) to the solution obtained in step (5), 20mL of acetone was added, centrifuged at 7000 rpm for 6min, the supernatant was removed, and then washed with cyclohexane: washing the solution with 1:3 ethanol, and centrifuging the solution three times to obtain the NaErF4@NaGdF4Dispersing the core-shell nano particles into 4mL of cyclohexane solvent to obtain a solution II for later use;
wherein, the water-solubility modification step is as follows: and (3) mixing the 4mL solution II obtained in the step (6) with a hydrochloric acid solution with the pH value of 3, stirring overnight, adding 8mL acetone for precipitation after the reaction is finished, centrifuging at 10000 r/min for 50min, washing with deionized water twice to obtain ligand-free up-conversion nanoparticles, and dispersing the ligand-free up-conversion nanoparticles into 10mL deionized water for storage.
The obtained product is named as Er @ Gd 1.
Further, in this example, the solution i was prepared as follows:
(1) under the argon atmosphere and the continuous stirring condition, adding 6mL of oleic acid, 15mL of 1-octadecene and 1mmol of erbium chloride hexahydrate into a round bottom three-necked bottle in sequence, and continuously stirring for 2 hours at room temperature after the addition is finished;
(2) heating the solution obtained in the step (1) to 180 ℃ at a heating rate of 15 ℃/min, stirring for 0.5h, enabling the solution to become pink transparent liquid, indicating that rare earth ions and oleic acid are successfully coordinated to form a complex which can be dissolved in 1-octadecene, and then cooling to room temperature;
(3) 100mg of NaOH powder and 148mg of NH4Adding the powder F into 10mL of methanol solvent, uniformly dispersing by ultrasonic, adding the obtained solution into the reaction solution obtained in the step (2), heating to 90 ℃, and keeping for 0.5h until the methanol in the solution is completely removed;
(4) introducing argon gas into the solution obtained in the step (3) for 60min to remove impurity gas and water vapor, then heating to 350 ℃, stirring for 1h, and then naturally cooling the solution to room temperature;
(5) adding 20mL of acetone into the solution obtained in the step (4), centrifuging for 10min at the rotating speed of 6000 rpm, removing the supernatant, and then adding cyclohexane: washing the mixed solution with the volume ratio of ethanol being 1:3, and centrifuging the solution for three times to obtain the NaErF4And (3) dispersing the naked core nano particles into 8mL of cyclohexane solvent to obtain a solution I for later use.
Example 2
A multi-mode core-shell nano contrast medium is prepared from NaErF4@NaGdF4Preparing core-shell nano particles and modifying water solubility;
NaErF4@NaGdF4the preparation of the core-shell nano-particles comprises the following steps:
(1) under the condition of argon atmosphere and continuous stirring, sequentially adding 6mL of oleic acid, 15mL of 1-octadecene and 0.5mmol of gadolinium chloride hexahydrate into a reaction bottle, and continuously stirring for 1h at room temperature after the addition is finished;
(2) heating the solution obtained in the step (1) to 180 ℃, stirring for 0.5h, and then cooling to room temperature;
(3) 50mg of NaOH powder and 74mg of NH4Adding the powder F into 5mL of methanol solution, uniformly dispersing by ultrasonic, adding the obtained solution into the reaction solution obtained in the step (2), heating to 90 ℃, and keeping for 0.5h until the methanol in the solution is completely removed;
(4) dropwise adding 2mL of solution I prepared in advance into the solution obtained in the step (3), heating to 60 ℃, and keeping for 2 hours until cyclohexane in the solution is completely removed;
(5) introducing argon gas into the solution obtained in the step (4) for 0.5h to remove impurity gas and water vapor, then heating to 250 ℃, keeping for 2h, and then naturally cooling the solution to room temperature;
(6) to the solution obtained in step (5) was added 20mL of acetone, centrifuged at 6500 rpm for 10min, the supernatant removed, and then washed with cyclohexane: washing the mixed solution with the volume ratio of ethanol being 1:3, and centrifuging the solution for three times to obtain the NaErF4@NaGdF4And dispersing the core-shell nano particles into 8mL of cyclohexane solvent to obtain a solution II for later use.
Wherein, the water-solubility modification step is as follows: and (3) mixing the 4mL solution II obtained in the step (6) with a hydrochloric acid solution with the pH value of 4, stirring overnight, adding 8mL acetone for precipitation after the reaction is finished, centrifuging at 11000 r/min for 20min, washing twice with deionized water to obtain ligand-free up-conversion nanoparticles, and dispersing the ligand-free up-conversion nanoparticles into 10mL deionized water for storage.
The obtained product is named as Er @ Gd 2.
Further, in this example, the preparation method of the solution i is as follows:
(1) under the argon atmosphere and the continuous stirring condition, adding 6mL of oleic acid, 15mL of 1-octadecene and 1mmol of erbium chloride hexahydrate into a round bottom three-necked bottle in sequence, and continuously stirring for 0.5h at room temperature after the addition is finished;
(2) heating the solution obtained in the step (1) to 150 ℃ at a heating rate of 12 ℃/min, stirring for 1h, enabling the solution to become pink transparent liquid, indicating that rare earth ions and oleic acid are successfully coordinated to form a complex soluble in 1-octadecene, and then cooling to room temperature;
(3) 100mg of NaOH powder and 148mg of NH4Adding the powder F into 10mL of methanol solvent, uniformly dispersing by ultrasonic, adding the obtained solution into the reaction solution obtained in the step (2), heating to 70 ℃, and keeping for 1h until the methanol in the solution is completely removed;
(4) introducing argon gas into the solution obtained in the step (3) for 60min to remove impurity gas and water vapor, then heating to 300 ℃, stirring for 1.5h, and then naturally cooling the solution to room temperature;
(5) to the solution obtained in step (4) was added 20mL of acetone, centrifuged at 7500 rpm for 6min, the supernatant was removed, and the mixture was washed with cyclohexane: washing the mixed solution with the volume ratio of ethanol being 1:3, and centrifuging the solution for three times to obtain the NaErF4The bare core nanoparticles were dispersed in 4mL cyclohexane solvent to obtain solution i for use.
NaErF prepared in this example4@NaGdF4The core-shell structure nanoparticles are scanned by a transmission electron microscope, and an obtained TEM image is shown in FIG. 1, and as can be seen from FIG. 1, the Er @ Gd2 nanoparticles are beta-type (hexagonal phase), have better dispersibility and uniform particle size distribution; FIG. 2 Dynamic Light Scattering (DLS) measured hydrated diameters of about 113 nm; meanwhile, the nano-particles are characterized by adopting an X-ray powder diffraction (XRD) instrument, and as shown in figure 3, the measured spectrum and NaErF with a hexagonal phase structure are obtained4Comparing the XRD standard spectrograms, and matching diffraction peak positions. The above results indicate that NaErF was successfully synthesized using the above preparation method4@NaGdF4Core-shell structured nanoparticles.
Example 3
A multi-mode core-shell nano contrast medium is prepared from NaErF4@NaGdF4Preparing core-shell nano particles and modifying water solubility;
NaErF4@NaGdF4the preparation of the core-shell nano-particles comprises the following steps:
(1) under the condition of argon atmosphere and continuous stirring, sequentially adding 6mL of oleic acid, 15mL of 1-octadecene and 0.75mmol of gadolinium chloride hexahydrate into a reaction bottle, and continuously stirring for 2 hours at room temperature after the addition is finished;
(2) heating the solution obtained in the step (1) to 120 ℃, stirring for 2h, and then cooling to room temperature;
(3) 75mg of NaOH powder and 111mg of NH4Adding F powder into 7.5mL of methanol solution, uniformly dispersing by ultrasonic wave, adding the obtained solution into the reaction solution obtained in the step (2), heating to 50 ℃, and keeping for 2 hours until the temperature is up to 50 DEG CUntil the methanol in the solution is completely removed;
(4) dropwise adding 2mL of solution I prepared in advance into the solution obtained in the step (3), heating to 70 ℃, and keeping for 1.5h until cyclohexane in the solution is completely removed;
(5) introducing argon gas into the solution obtained in the step (4) for 2 hours to remove impurity gas and water vapor, then heating to 350 ℃, keeping for 0.5 hour, and then naturally cooling the solution to room temperature;
(6) to the solution obtained in step (5) was added 20mL of acetone, centrifuged at 8000 rpm for 8min, the supernatant removed, and then washed with cyclohexane: washing the solution with 1:3 ethanol, and centrifuging the solution three times to obtain the NaErF4@NaGdF4And dispersing the core-shell nano particles into 4mL of cyclohexane solvent to obtain a solution II for later use.
Wherein, the water-solubility modification step is as follows: and (3) mixing the 4mL solution II obtained in the step (6) with a hydrochloric acid solution with the pH value of 5, stirring overnight, adding 8mL acetone for precipitation after the reaction is finished, centrifuging at 10000 r/min for 30min, washing twice with deionized water to obtain ligand-free up-conversion nanoparticles, and dispersing the ligand-free up-conversion nanoparticles into 10mL deionized water for storage.
The obtained product is named as Er @ Gd 3.
Further, in this example, the preparation method of the solution i is as follows:
(1) under the argon atmosphere and the continuous stirring condition, adding 6mL of oleic acid, 15mL of 1-octadecene and 1mmol of erbium chloride hexahydrate into a round bottom three-necked bottle in sequence, and continuously stirring for 1h at room temperature after the addition is finished;
(2) heating the solution obtained in the step (1) to 120 ℃ at a heating rate of 10 ℃/min, stirring for 2h to obtain pink transparent liquid, indicating that rare earth ions and oleic acid are successfully coordinated to form a complex soluble in 1-octadecene, and then cooling to room temperature;
(3) 100mg of NaOH powder and 148mg of NH4Adding the powder F into 10mL of methanol solvent, uniformly dispersing by ultrasonic, adding the obtained solution into the reaction solution obtained in the step (2), heating to 50 ℃, and keeping for 2 hours until the methanol in the solution is completely removed;
(4) introducing argon gas into the solution obtained in the step (3) for 60min to remove impurity gas and water vapor, then heating to 260 ℃, stirring for 2h, and then naturally cooling the solution to room temperature;
(5) to the solution obtained in step (4) was added 20mL of acetone, centrifuged at 8000 rpm for 5min, the supernatant removed, and then washed with cyclohexane: washing the mixed solution with the volume ratio of ethanol being 1:3, and centrifuging the solution for three times to obtain the NaErF4And (3) dispersing the naked core nano particles into 8mL of cyclohexane solvent to obtain a solution I for later use.
Example 4
Three products of Er @ Gd1, Er @ Gd2 and Er @ Gd3 prepared in examples 1-3 are characterized by a 7T nuclear magnetic resonance imager to study NaErF with different core-shell ratios4@NaGdF4The lateral relaxation efficiency of the nanoparticles.
The test method comprises the following steps:
1. respectively weighing three products of Er @ Gd1, Er @ Gd2 and Er @ Gd3, and preparing to-be-detected liquid (c (Gd) with different concentrations of different products3+) 4.9,9.8,24.5,49mM) sample, sonicated for 30min, and loaded into a 5mM nuclear magnetic tube;
2. transverse relaxation time (T2) values were determined. T2-weighted NMR in vitro water tube imaging was performed on the samples using a 7T MR scanner. Instrument test parameters: TR 2500ms, TE 132ms, matrix 64 × 64, FOV 3.00cm, slice thickness 1.0 mm.
And (3) test results:
respectively obtaining Gd of three products of Er @ Gd1, Er @ Gd2 and Er @ Gd33+The concentration is plotted against the transverse relaxation rate (1/T2) to obtain a straight line, the slope of the straight line is the transverse relaxation efficiency (r2), and the r2 value is calculated and determined, as shown in FIG. 4, the T2 of Er @ Gd2 which is screened out is the strongest in contrast ability.
Example 5
Three products of Er @ Gd1, Er @ Gd2 and Er @ Gd3 prepared in examples 1-3 are characterized by Micro-CT to research NaErF with different core-shell ratios4@NaGdF4The X-ray attenuation capability of the nanoparticles.
The test method comprises the following steps:
1. respectively weighing Er @Preparing three products of Gd1, Er @ Gd2 and Er @ Gd3 to prepare solutions to be detected (c (Gd) with different concentrations of different products3+) 4.9,9.8,24.5,49mM) sample, sonicated for 30min, and loaded into a 5mM nuclear magnetic tube;
2. and opening the Micro-CT, preheating for 20min, putting the nuclear magnetic tube into the instrument, and testing to obtain the HU value. The imaging parameters of the instrument are as follows: image Pixel size 35 μm, U50 kVp, I500 μ a.
And (3) test results:
and (3) making a function of the CT value and the concentration of the probe, and calculating the slope of the function to obtain a graph 5, so that the Er @ Gd2 nano-particle has the strongest CT contrast capability.
Example 6
The up-conversion fluorescence spectra of three products, namely Er @ Gd1, Er @ Gd2 and Er @ Gd3, prepared in examples 1 to 3 were tested by using an infrared fiber coupled laser and a QE600 spectrometer.
The test method comprises the following steps:
1. respectively weighing three products of Er @ Gd1, Er @ Gd2 and Er @ Gd3, dissolving 2mg in 1mL of deionized water to prepare an aqueous solution, and performing ultrasonic treatment for 30min to uniformly disperse the aqueous solution;
2. under the excitation of near infrared light of 980nm, an infrared fiber coupled laser and a QE600 spectrometer are used for testing to obtain the up-conversion fluorescence spectra of three products, as shown in figure 6, the strongest emission part of the up-conversion nano particles is 660nm, wherein the property up-conversion luminescence capacity of the Er @ Gd2 nano particles is strongest.
The above embodiments are only for illustrating the technical concept and features of the present invention, and the purpose thereof is to enable those skilled in the art to understand the contents of the present invention and implement the present invention accordingly, and not to limit the protection scope of the present invention accordingly. All equivalent changes or modifications made in accordance with the spirit of the present disclosure are intended to be covered by the scope of the present disclosure.
Claims (9)
1. NaErF4@NaGdF4The application of the core-shell nano particles in preparing a multi-modal contrast agent is characterized in that the multi-modal contrast agent is simultaneously used for MRI, CT and up-conversion luminescence imaging; the multimode isThe preparation of the contrast agent comprises NaErF4@NaGdF4Preparing core-shell nano particles and modifying water solubility;
the NaErF4@NaGdF4The preparation of the core-shell nano-particles comprises the following steps:
(1) sequentially adding oleic acid, 1-octadecene and gadolinium chloride hexahydrate into a reaction bottle under the condition of argon atmosphere and continuous stirring, and continuously stirring for 0.5-2h at room temperature after the addition is finished;
(2) heating the solution obtained in the step (1) to 120-180 ℃, stirring for 0.5-2h, and then cooling to room temperature;
(3) mixing NaOH powder and NH4Adding the powder F into a methanol solution, uniformly dispersing by ultrasonic, adding the obtained solution into the reaction solution obtained in the step (2), heating to 50-90 ℃, and keeping for 0.1-2 h;
(4) dropwise adding the solution I prepared in advance into the solution obtained in the step (3), heating to 50-90 ℃, and keeping for 0.5-2 h;
(5) introducing argon into the solution obtained in the step (4), heating to 200-350 ℃, keeping the temperature for 0.5-2h, and then cooling the solution to room temperature;
(6) adding acetone into the solution obtained in the step (5), centrifuging and cleaning to obtain the NaErF4@NaGdF4Dispersing the core-shell nano particles into a cyclohexane solvent to obtain a solution II for later use;
the water-soluble modification steps are as follows: and (4) mixing the solution II obtained in the step (6) with a hydrochloric acid solution, stirring, adding acetone for precipitation, centrifuging, washing to obtain ligand-free up-conversion nanoparticles, and dispersing the ligand-free up-conversion nanoparticles into deionized water for storage.
2. A NaErF according to claim 14@NaGdF4The application of the core-shell nano particles in the preparation of the multi-modal contrast agent is characterized in that the preparation method of the solution I is as follows:
(1) sequentially adding oleic acid, 1-octadecene and erbium chloride hexahydrate into a reaction bottle under the condition of argon atmosphere and continuous stirring, and continuously stirring for 0.5-2 hours at room temperature after the addition is finished;
(2) heating the solution obtained in the step (1) to 120-180 ℃ at the heating rate of 10-15 ℃/min, stirring for 0.5-2h, and then cooling to room temperature;
(3) mixing NaOH powder and NH4Adding the powder F into a methanol solvent, uniformly dispersing by ultrasonic, adding the obtained solution into the reaction solution obtained in the step (2), heating to 50-90 ℃, and keeping for 0.1-2 h;
(4) introducing argon into the solution obtained in the step (3), heating to 200-350 ℃, stirring for 0.5-2h, and then cooling the solution to room temperature;
(5) adding acetone into the solution obtained in the step (4), centrifuging and cleaning to obtain the NaErF4And (3) dispersing the bare-core nano particles into a cyclohexane solvent to obtain a solution I for later use.
3. A NaErF according to claim 14@NaGdF4The application of the core-shell nano-particles in the preparation of the multi-modal contrast agent is characterized in that NaErF4@NaGdF4In the preparation of the core-shell nano-particles, the dosage of gadolinium chloride hexahydrate is 200-500mg, the dosage of oleic acid is 5-10mL, the dosage of 1-octadecene is 10-25mL, the dosage of NaOH powder is 25-200mg, and NH is added4The dosage of the F powder is 20-200mg, the dosage of the methanol is 5-20mL, the dosage of the acetone is 10-30mL, and the dosage of the cyclohexane in the solution II is 2-10 mL.
4. A NaErF according to claim 14@NaGdF4The application of the core-shell nano-particles in the preparation of the multi-modal contrast agent is characterized in that NaErF4@NaGdF4The addition amount of the solution I in the preparation of the core-shell nano-particles is 1-5 mL.
5. A NaErF according to claim 14@NaGdF4The application of the core-shell nano-particles in the preparation of the multi-modal contrast agent is characterized in that NaErF4@NaGdF4In the preparation of the core-shell nano-particles, the centrifugal rotating speed is 6500-8000 rpm, and the centrifugal time is 4-10 min.
6. Root of herbaceous plantA NaErF according to claim 24@NaGdF4The application of the core-shell nano-particles in the preparation of the multi-modal contrast agent is characterized in that in the preparation of the solution I, the dosage of erbium chloride hexahydrate is 200-500mg, the dosage of oleic acid is 5-10mL, the dosage of 1-octadecene is 10-25mL, the dosage of NaOH powder is 50-200mg, and NH is added4The dosage of the F powder is 100-300mg, the dosage of the methanol is 5-20mL, and the dosage of the acetone is 10-30 mL.
7. A NaErF according to claim 24@NaGdF4The application of the core-shell nano particles in the preparation of the multi-modal contrast agent is characterized in that the volume ratio of the solvent used in the cleaning process is 1:3, cyclohexane and ethanol.
8. A NaErF according to claim 24@NaGdF4The application of the core-shell nano-particles in the preparation of the multi-modal contrast agent is characterized in that in the preparation of the solution I, the centrifugal rotating speed is 6000-8000 rpm, the centrifugal time is 5-10min, and the dosage of cyclohexane in the solution I is 2-10 mL.
9. A NaErF according to claim 14@NaGdF4The application of the core-shell nano-particles in the preparation of the multi-modal contrast agent is characterized in that the centrifugal rotation speed in the water-soluble modification is 10000-11000 r/min, the centrifugal time is 10-60min, the addition amount of acetone is 5-20mL, and the pH value of a hydrochloric acid solution is 3-5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110025832.9A CN112704745A (en) | 2021-01-08 | 2021-01-08 | NaErF4@NaGdF4Application of core-shell nanoparticles in preparation of multi-modal contrast agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110025832.9A CN112704745A (en) | 2021-01-08 | 2021-01-08 | NaErF4@NaGdF4Application of core-shell nanoparticles in preparation of multi-modal contrast agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112704745A true CN112704745A (en) | 2021-04-27 |
Family
ID=75548658
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110025832.9A Pending CN112704745A (en) | 2021-01-08 | 2021-01-08 | NaErF4@NaGdF4Application of core-shell nanoparticles in preparation of multi-modal contrast agent |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112704745A (en) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102391874A (en) * | 2011-09-21 | 2012-03-28 | 中国科学院上海硅酸盐研究所 | NaYF4-based fluorescent nano particles with double effects and preparation method thereof |
| CN103173222A (en) * | 2013-03-15 | 2013-06-26 | 吉林大学 | Water soluble NaYF4@NaGdF4 nanocrystalline with upconversion core-shell structure and preparation method thereof |
| CN106620700A (en) * | 2016-12-28 | 2017-05-10 | 中国科学院长春光学精密机械与物理研究所 | Compound and application thereof |
| US20180208688A1 (en) * | 2017-01-20 | 2018-07-26 | City University Of Hong Kong | Method for surface modification of nanoparticles |
| CN109983080A (en) * | 2016-11-18 | 2019-07-05 | 维也纳农业大学 | The ligand substituting method of surfaces of metal nanoparticles |
| CN110358530A (en) * | 2019-08-09 | 2019-10-22 | 苏州大学 | A kind of rare earth core shell nanoparticles and its preparation and application |
| CN111426658A (en) * | 2019-09-23 | 2020-07-17 | 湖北大学 | Method for detecting thrombin by using quantum dot sensitized up-conversion nano material |
| CN112080278A (en) * | 2020-09-21 | 2020-12-15 | 东北林业大学 | Up/down conversion dual-mode luminescent nanocrystal and preparation method and application thereof |
-
2021
- 2021-01-08 CN CN202110025832.9A patent/CN112704745A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102391874A (en) * | 2011-09-21 | 2012-03-28 | 中国科学院上海硅酸盐研究所 | NaYF4-based fluorescent nano particles with double effects and preparation method thereof |
| CN103173222A (en) * | 2013-03-15 | 2013-06-26 | 吉林大学 | Water soluble NaYF4@NaGdF4 nanocrystalline with upconversion core-shell structure and preparation method thereof |
| CN109983080A (en) * | 2016-11-18 | 2019-07-05 | 维也纳农业大学 | The ligand substituting method of surfaces of metal nanoparticles |
| CN106620700A (en) * | 2016-12-28 | 2017-05-10 | 中国科学院长春光学精密机械与物理研究所 | Compound and application thereof |
| US20180208688A1 (en) * | 2017-01-20 | 2018-07-26 | City University Of Hong Kong | Method for surface modification of nanoparticles |
| CN110358530A (en) * | 2019-08-09 | 2019-10-22 | 苏州大学 | A kind of rare earth core shell nanoparticles and its preparation and application |
| CN111426658A (en) * | 2019-09-23 | 2020-07-17 | 湖北大学 | Method for detecting thrombin by using quantum dot sensitized up-conversion nano material |
| CN112080278A (en) * | 2020-09-21 | 2020-12-15 | 东北林业大学 | Up/down conversion dual-mode luminescent nanocrystal and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Shi et al. | A new near-infrared persistent luminescence nanoparticle as a multifunctional nanoplatform for multimodal imaging and cancer therapy | |
| Yang et al. | Hydrothermal synthesis of NaLuF4: 153Sm, Yb, Tm nanoparticles and their application in dual-modality upconversion luminescence and SPECT bioimaging | |
| Sun et al. | Upconversion nanophosphors NaLuF4: Yb, Tm for lymphatic imaging in vivo by real-time upconversion luminescence imaging under ambient light and high-resolution X-ray CT | |
| Wang et al. | Dye‐sensitized downconversion nanoprobes with emission beyond 1500 nm for ratiometric visualization of cancer redox state | |
| Shi et al. | X‐ray‐induced persistent luminescence promotes ultrasensitive imaging and effective inhibition of orthotopic hepatic tumors | |
| Mignot et al. | A Top‐Down synthesis route to ultrasmall multifunctional Gd‐Based silica nanoparticles for theranostic applications | |
| Liu et al. | Controlled synthesis of uniform and monodisperse upconversion core/mesoporous silica shell nanocomposites for bimodal imaging | |
| Ge et al. | New nanoplatforms based on UCNPs linking with polyhedral oligomeric silsesquioxane (POSS) for multimodal bioimaging | |
| Sun et al. | Radioisotope post-labeling upconversion nanophosphors for in vivo quantitative tracking | |
| Wu et al. | Lanthanide-based nanocrystals as dual-modal probes for SPECT and X-ray CT imaging | |
| Xia et al. | Enhanced dual contrast agent, Co2+-doped NaYF4: Yb3+, Tm3+ nanorods, for near infrared-to-near infrared upconversion luminescence and magnetic resonance imaging | |
| Wu et al. | Silica‐encapsulated Gd3+‐aggregated gold nanoclusters for in vitro and in vivo multimodal cancer imaging | |
| Li et al. | In vitro photodynamic therapy based on magnetic-luminescent Gd 2 O 3: Yb, Er nanoparticles with bright three-photon up-conversion fluorescence under near-infrared light | |
| CN110373193B (en) | Preparation and application of homoenergetic rare earth luminescent probe based on luminescent life change | |
| CN108760692B (en) | Composite nano probe and method for detecting living body ratio imaging by using same | |
| CN113797357B (en) | Drug delivery system, preparation method and application thereof | |
| Maurya et al. | Assessment of colloidal NaGdF4: Er3+/Yb3+ upconversion phosphor as contrast enhancer for optical coherence tomography | |
| Zhao et al. | A magnetofluorescent boron-doped carbon dots as a metal-free bimodal probe | |
| Wang et al. | A nanocomposite of rare earth upconversion nanoparticles and nanodiamonds for dual-mode imaging and drug delivery | |
| Wang et al. | Nanostructures based on vanadium disulfide growing on UCNPs: simple synthesis, dual-mode imaging, and photothermal therapy | |
| Fathi et al. | Near-infrared emitting dual-stimuli-responsive carbon dots from endogenous bile pigments | |
| Wang et al. | LiGa5O8: Cr3+@ PEG nanomaterials with near-infrared-persistent luminescence for bioimaging applications | |
| Li et al. | Potential detection of cancer with fluorinated silicon nanoparticles in 19 F MR and fluorescence imaging | |
| Yu et al. | Microwave–assisted synthesis of water–disperse and biocompatible NaGdF4: Yb, Ln@ NaGdF4 nanocrystals for UCL/CT/MR multimodal imaging | |
| Chen et al. | Preparation of AIEgen-based near-infrared afterglow luminescence nanoprobes for tumor imaging and image-guided tumor resection |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210427 |