CN111110870A - Water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster and preparation method and application thereof - Google Patents
Water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster and preparation method and application thereof Download PDFInfo
- Publication number
- CN111110870A CN111110870A CN201911136194.7A CN201911136194A CN111110870A CN 111110870 A CN111110870 A CN 111110870A CN 201911136194 A CN201911136194 A CN 201911136194A CN 111110870 A CN111110870 A CN 111110870A
- Authority
- CN
- China
- Prior art keywords
- gadolinium
- iron oxide
- water
- magnetic iron
- biocompatible
- 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.)
- Granted
Links
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 title claims abstract description 168
- 230000005291 magnetic effect Effects 0.000 title claims abstract description 93
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 229910052688 Gadolinium Inorganic materials 0.000 claims abstract description 25
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 claims abstract description 24
- 229920000249 biocompatible polymer Polymers 0.000 claims abstract description 21
- 238000002595 magnetic resonance imaging Methods 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 9
- 239000002872 contrast media Substances 0.000 claims abstract description 6
- 239000002202 Polyethylene glycol Substances 0.000 claims description 22
- 229920001223 polyethylene glycol Polymers 0.000 claims description 22
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 18
- HOIQWTMREPWSJY-GNOQXXQHSA-K iron(3+);(z)-octadec-9-enoate Chemical compound [Fe+3].CCCCCCCC\C=C/CCCCCCCC([O-])=O.CCCCCCCC\C=C/CCCCCCCC([O-])=O.CCCCCCCC\C=C/CCCCCCCC([O-])=O HOIQWTMREPWSJY-GNOQXXQHSA-K 0.000 claims description 16
- 229940049964 oleate Drugs 0.000 claims description 16
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- 238000010438 heat treatment Methods 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000012295 chemical reaction liquid Substances 0.000 claims description 6
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 239000002105 nanoparticle Substances 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 2
- 239000003208 petroleum Substances 0.000 claims description 2
- 229920002521 macromolecule Polymers 0.000 claims 1
- 239000002243 precursor Substances 0.000 abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 4
- 229910052751 metal Inorganic materials 0.000 abstract description 3
- 239000002184 metal Substances 0.000 abstract description 3
- 230000001105 regulatory effect Effects 0.000 abstract description 3
- 239000012692 Fe precursor Substances 0.000 abstract description 2
- 238000000354 decomposition reaction Methods 0.000 abstract description 2
- 238000011065 in-situ storage Methods 0.000 abstract description 2
- 239000002798 polar solvent Substances 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 239000002245 particle Substances 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000002524 electron diffraction data Methods 0.000 description 8
- 238000003917 TEM image Methods 0.000 description 7
- 238000002296 dynamic light scattering Methods 0.000 description 7
- 238000010521 absorption reaction Methods 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- SZVJSHCCFOBDDC-UHFFFAOYSA-N ferrosoferric oxide Chemical compound O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 description 5
- 239000002159 nanocrystal Substances 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000012046 mixed solvent Substances 0.000 description 4
- 239000002086 nanomaterial Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 2
- 238000005452 bending Methods 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 206010000871 Acute monocytic leukaemia Diseases 0.000 description 1
- 229910017135 Fe—O Inorganic materials 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- -1 Gadolinium ions Chemical class 0.000 description 1
- 208000035489 Monocytic Acute Leukemia Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000005294 ferromagnetic effect Effects 0.000 description 1
- IQGAADOKZGEEQE-LNTINUHCSA-K gadolinium acetylacetonate Chemical compound [Gd+3].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O IQGAADOKZGEEQE-LNTINUHCSA-K 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- LZKLAOYSENRNKR-LNTINUHCSA-N iron;(z)-4-oxoniumylidenepent-2-en-2-olate Chemical compound [Fe].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O LZKLAOYSENRNKR-LNTINUHCSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000002122 magnetic nanoparticle Substances 0.000 description 1
- 230000005389 magnetism Effects 0.000 description 1
- 230000005415 magnetization Effects 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229940031182 nanoparticles iron oxide Drugs 0.000 description 1
- 231100001083 no cytotoxicity Toxicity 0.000 description 1
- 239000002405 nuclear magnetic resonance imaging agent Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000005476 size effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000005641 tunneling Effects 0.000 description 1
- 238000005303 weighing 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
- A61K49/06—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
-
- 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
- A61K49/1827—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]
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01G—COMPOUNDS CONTAINING METALS NOT COVERED BY SUBCLASSES C01D OR C01F
- C01G49/00—Compounds of iron
- C01G49/02—Oxides; Hydroxides
- C01G49/08—Ferroso-ferric oxide [Fe3O4]
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/50—Agglomerated particles
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/60—Particles characterised by their size
- C01P2004/64—Nanometer sized, i.e. from 1-100 nanometer
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nanotechnology (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Radiology & Medical Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Crystallography & Structural Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Inorganic Chemistry (AREA)
- Biophysics (AREA)
- Immunology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The invention discloses a water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster and a preparation method and application thereof. Dissolving a gadolinium precursor, an iron precursor and a biocompatible polymer in a high-boiling-point nonpolar or weakly polar solvent, forming a gadolinium-doped magnetic iron oxide nanocluster by a high-temperature decomposition method, modifying the biocompatible polymer on the surface of the nanocluster in situ, and regulating the content of gadolinium in the nanocluster by regulating the proportion of the metal precursor. The method has the characteristics of simple process, simple and convenient operation and low cost of raw materials, and the obtained water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster has the advantages of superparamagnetism, good water solubility and high relaxation rate, and can be used as a contrast agent to be applied to magnetic resonance imaging.
Description
Technical Field
The invention relates to a nanocluster and a preparation method and application thereof, in particular to a water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster and a preparation method and application thereof, and belongs to the technical field of inorganic nano materials.
Background
The nano material has the effects of surface effect, volume effect, quantum size effect, dielectric confinement effect, macroscopic quantum tunneling effect and the like, and has good substance compared with small-sized substances such as atoms, molecules and the likePhysical and chemical properties. The magnetic iron oxide nano material has unique superparamagnetism and biocompatibility, becomes a nano material which is widely applied in the medical field at present, and has great advantages in the aspects of magnetic resonance imaging and tumor treatment. Magnetic nanoparticles above the critical dimension (about 25 nm) can switch from superparamagnetic to ferromagnetic, making them unsuitable for biomedical applications. The magnetic iron oxide nanocluster is a secondary structure consisting of a primary structure of iron oxide nanoparticles, and the nanoparticles have superparamagnetism, so that the nanocluster also retains the superparamagnetism, has stronger magnetic performance than the primary structure of the nanoparticles, and can avoid the aggregation of the particle clusters caused by residual magnetism. The magnetic iron oxide particle cluster is a soft magnetic substance, and when other metal ions are doped in the magnetic iron oxide crystal lattice, the structure, the physical and chemical properties and the magnetic properties of the nanocluster can be effectively changed. Gadolinium ions are special ions, have large magnetic moments and excellent magnetic resonance imaging effect, and are used as common magnetic resonance imaging contrast agents. In addition, the spin sequence of gadolinium can generate a local magnetic field in the same direction as that of magnetic iron oxide, so that the local magnetic field strength and nonuniformity are remarkably increased, and T is further improved1And T2Magnetic resonance imaging effect. In recent years, some groups of subjects have studied gadolinium-doped magnetic iron oxide nanoclusters, and Si et al obtained gadolinium-doped magnetic iron oxide nanoclusters by reacting iron acetylacetonate, gadolinium acetylacetonate, polyethylene glycol, and polyvinylpyrrolidone in an autoclave for 72 hours [ Chemical Engineering Journal,2019,360:289 ]]The synthesis method has longer reaction time. Wang et al used stearic acid modified polyethyleneimine to assemble gadolinium doped nanocrystals into nanoclusters in aqueous phase [ nanoscales, 2013,5(17):8098]This synthesis is complex and requires two steps to complete.
At present, no preparation method of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster in the prior art can realize one-pot preparation and has high yield, and the obtained nanocluster has excellent water solubility and biocompatibility. Therefore, the development of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster with low energy consumption and strong reaction controllability is one of the important points of research.
Disclosure of Invention
The invention aims to provide a water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster and a preparation method and application thereof. The prepared nanocluster is soluble in water phase solution, has good colloidal stability and higher relaxation rate and magnetic saturation strength, and can be applied to magnetic resonance imaging.
In order to achieve the purpose, a gadolinium precursor, an iron precursor and a biocompatible polymer are dissolved in a high-boiling-point nonpolar or weak-polar solvent, the biocompatible polymer is modified in situ on the surface of a nanocluster while the gadolinium-doped magnetic iron oxide nanocluster is formed by a high-temperature decomposition method, and the content of gadolinium in the nanocluster is regulated and controlled by adjusting the proportion of the metal precursor. Specifically, the invention adopts the following technical means:
the invention provides a water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster, which is a secondary structure with the size of 50-200 nanometers and comprises primary structure nanoparticles with the size of 2-10 nanometers and a biocompatible polymer coated on the surface of the primary structure nanoparticles; the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster is prepared from iron oleate, gadolinium oleate and a biocompatible polymer, wherein the mass ratio of the gadolinium oleate to the iron oleate to the biocompatible polymer is 0.1-0.5: 1: 2-10.
Preferably, the ratio of the gadolinium oleate to the iron oleate to the biocompatible polymer is 0.2:1: 3.
Preferably, the biocompatible polymer is selected from polyethylene glycol, carboxyl-terminated polyethylene glycol, methoxy polyethylene glycol, carboxylated methoxy polyethylene glycol or branched polyethylene glycol, and the number average molecular weight is 400-50000.
The invention also provides a preparation method of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster, which comprises the following steps:
a. gadolinium oleate, iron oleate and biocompatible polymer are added into the phenyl ether;
b. heating the reaction solution to 100-120 ℃ in a nitrogen atmosphere, keeping the temperature for 0.5-2 hours, continuously heating to 200 ℃ under the stirring condition, keeping the temperature for 0.5-1 hour, then continuously heating to 259 ℃, and reacting for 0.5-12 hours;
c. and after the reaction liquid is cooled, adding a solvent for washing, centrifuging and drying to obtain the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster.
Preferably, the weight ratio of the gadolinium oleate to the iron oleate to the biocompatible polymer in the step a is 0.1-0.5: 1: 2-10; more preferably, the ratio of the gadolinium oleate to the iron oleate to the biocompatible polymer in step a is 0.2:1: 3.
Preferably, the biocompatible polymer in step a is selected from polyethylene glycol, carboxyl-terminated polyethylene glycol, methoxypolyethylene glycol, carboxylated methoxypolyethylene glycol or branched polyethylene glycol, and the number average molecular weight is 400-50000.
Preferably, the stirring speed in step b is: 400-1000 rpm.
Preferably, the solvent in step c is one or more selected from ethanol, diethyl ether, acetone, petroleum ether, ethyl acetate and hexane.
The invention also provides application of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster as a contrast agent in magnetic resonance imaging.
Compared with the prior art, the invention has the beneficial effects that:
the invention carries out biocompatibility modification on the surface of the nanocluster while forming the nanocluster, and has the advantages of simple preparation process, simple and convenient operation and low raw material cost. The obtained water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster has the advantages of superparamagnetism, good biocompatibility and high relaxation rate, can be highly dissolved and stably dispersed in a water phase, has excellent superparamagnetism, has higher saturation magnetization, and can be quickly recovered under a magnetic field. Therefore, the nanoclusters of the present invention may be used as a contrast agent in magnetic resonance imaging, and may also be used in applications such as cell separation.
Drawings
Fig. 1 is an X-ray diffraction (XRD) pattern of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in examples 1 to 4.
FIG. 2 is an infrared spectrum of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in examples 1 to 4.
Fig. 3 is a Transmission Electron Microscope (TEM) image and a high resolution transmission electron microscope (HR-TEM) image of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster prepared in example 1.
Fig. 4 is a TEM image and an HR-TEM image of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster prepared in example 2.
Fig. 5 is a TEM image and an HR-TEM image of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster prepared in example 3.
Fig. 6 is a TEM image and an HR-TEM image of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster prepared in example 4.
Fig. 7 is an electron diffraction pattern of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 1.
Fig. 8 is an electron diffraction pattern of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 2.
Fig. 9 is an electron diffraction pattern of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 3.
Fig. 10 is an electron diffraction pattern of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 4.
Fig. 11 is a graph of Dynamic Light Scattering (DLS) of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in examples 1 to 4.
Fig. 12 is a DLS diagram of the nano water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 3 in sodium chloride solutions of different concentrations.
Fig. 13 is a DLS graph and a Zeta potential test line graph of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster prepared in example 3 with the standing time.
Fig. 14 is a graph of a Vibrating Sample Magnetometer (VSM) of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in examples 1 to 4.
Fig. 15 is a graph of the relaxation rate of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 3.
Fig. 16 shows the cytotoxicity results of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 3 on human acute monocytic leukemia cells (THP-1).
Fig. 17 is an in vivo MRI image of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster prepared in example 3 in a laboratory mouse.
Detailed Description
The invention will be further described with reference to specific embodiments, and the advantages and features of the invention will become apparent as the description proceeds. These examples are illustrative only and do not limit the scope of the present invention in any way. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be made without departing from the spirit and scope of the invention.
Example 1
The preparation method of the 62 nanometer water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster comprises the following steps:
respectively weighing 0.2mmol of gadolinium oleate, 2mmol of iron oleate and 6mmol of carboxyl-terminated polyethylene glycol (the number average molecular weight Mn is 600) and 10g of phenyl ether, placing in a three-neck flask, introducing nitrogen, heating to 110 ℃, keeping at 110 ℃ for 0.5 hour, then heating to 200 ℃, and keeping at 200 ℃ for 0.5 hour; finally, heating was continued to 259 ℃ for 1 hour. And after the reaction liquid is cooled to room temperature, washing and centrifugally separating the product by using a mixed solvent of 10mL of hexane and 30mL of acetone, and finally drying to obtain the 62-nanometer water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster.
Example 2
The preparation method of the 63 nanometer water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster comprises the following steps:
0.3mmol of gadolinium oleate, 2mmol of iron oleate and 6mmol of carboxyl-terminated polyethylene glycol (Mn 600) and 10g of phenyl ether are respectively weighed and placed in a three-neck flask, nitrogen is introduced, the mixture is heated to 110 ℃ and kept for 0.5 hour at the temperature of 110 ℃, then heated to 200 ℃ and kept for 0.5 hour at the temperature of 200 ℃; finally, heating was continued to 259 ℃ for 1 hour. And after the reaction liquid is cooled to room temperature, washing and centrifugally separating the product by using a mixed solvent of 10mL of hexane and 30mL of acetone, and finally drying to obtain the 63-nanometer water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster.
Example 3
The preparation method of the 65 nanometer water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster comprises the following steps:
0.4mmol of gadolinium oleate, 2mmol of iron oleate and 6mmol of carboxyl-terminated polyethylene glycol (Mn 600) and 10g of phenyl ether are respectively weighed and placed in a three-neck flask, nitrogen is introduced, the mixture is heated to 110 ℃ and kept for 0.5 hour at the temperature of 110 ℃, then heated to 200 ℃ and kept for 0.5 hour at the temperature of 200 ℃; finally, heating was continued to 259 ℃ for 1 hour. And after the reaction liquid is cooled to room temperature, washing and centrifugally separating the product by using a mixed solvent of 10mL of hexane and 30mL of acetone, and finally drying to obtain the 65-nanometer water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster.
Example 4
The preparation method of the 59 nanometer water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster comprises the following steps:
0.5mmol of gadolinium oleate, 2mmol of iron oleate and 10mmol of carboxyl-terminated polyethylene glycol (Mn 600) and 10g of phenyl ether are respectively weighed and placed in a three-neck flask, nitrogen is introduced, the mixture is heated to 110 ℃ and kept at the temperature of 110 ℃ for 0.5 hour, then heated to 200 ℃ and kept at the temperature of 200 ℃ for 0.5 hour; finally, heating was continued to 259 ℃ for 1 hour. And after the reaction liquid is cooled to room temperature, washing and centrifugally separating the product by using a mixed solvent of 10mL of hexane and 30mL of acetone, and finally drying to obtain the 59 nanometer water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster.
Examples of the experiments
The water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in the above embodiments 1 to 4 are characterized, and the results are as follows:
1. the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 1, example 2, example 3 and example 4 were characterized by X-ray diffraction, and the results are shown in fig. 1.
The results show that XRD patterns of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in examples 1, 2, 3 and 4 correspond to standard cards (JCPDS No.19-0629) one by one, and the peak intensities and the ratios therebetween are substantially consistent with those of the standard cards, and no other peaks are present, which indicates that the bulk structure of the prepared water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters is composed of ferroferric oxide and the crystal growth is good.
2. Fourier transform infrared spectroscopy analysis was performed on the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 1, example 2, example 3, and example 4, and the results are shown in fig. 2.
The results show that 1110cm of infrared spectrum of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 1, example 2, example 3 and example 4-1The absorption peak corresponds to the stretching vibration of C-O-C; 1350cm-1And 1450cm-1The absorption peak at corresponds to CH2Stretching vibration and bending vibration of; 2870cm-1And 2920cm-1The absorption peak corresponds to the stretching vibration and the bending vibration of CH; 1730cm-1The absorption peak corresponds to the stretching vibration of C ═ O; 1580cm-1The absorption peak at (a) is red-shifted from C ═ O with the carboxyl group, because the oxygen atom interacts with the metal surface, converting the carboxylic acid to carboxylate; 569cm-1The absorption peak at (B) corresponds to the stretching vibration of Fe-O. The above results demonstrate that gadolinium-doped magnetic iron oxide nanoclustersThe cluster surface was successfully modified with carboxyl-terminated polyethylene glycol.
3. Fig. 3 is a TEM image and an HR-TEM image of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster prepared in example 1. The results showed that the nanoclusters had an average particle size of 62 nm, consisted of 4.2 nm particles, and the lattice fringe spacing of the nanocrystals was 0.11 nm.
4. Fig. 4 is a TEM image and an HR-TEM image of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster prepared in example 2. The results showed that the nanoclusters had an average particle size of 63 nm, consisted of 4.0 nm particles, and the lattice fringe spacing of the nanocrystals was 0.26 nm.
5. Fig. 5 is a TEM image and an HR-TEM image of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster prepared in example 3. The results showed that the nanoclusters had an average particle size of 65 nm, consisted of 3.7 nm particles, and the lattice fringe spacing of the nanocrystals was 0.15 nm.
6. Fig. 6 is a TEM image and an HR-TEM image of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster prepared in example 4. The results showed that the nanoclusters had an average particle size of 59 nm, consisted of 3.0 nm particles, and the lattice fringe spacing of the nanocrystals was 0.17 nm.
7. Fig. 7 is an electron diffraction pattern of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 1. The result shows that the crystallization state of the nanocluster is good, and the obtained diffraction ring crystal face data are consistent with those of ferroferric oxide.
8. Fig. 8 is an electron diffraction pattern of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 2. The result shows that the crystallization state of the nanocluster is good, and the obtained diffraction ring crystal face data are consistent with those of ferroferric oxide.
9. Fig. 9 is an electron diffraction pattern of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 3. The result shows that the crystallization state of the nanocluster is good, and the obtained diffraction ring crystal face data are consistent with those of ferroferric oxide.
10. Fig. 10 is an electron diffraction pattern of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 4. The result shows that the crystallization state of the nanocluster is good, and the obtained diffraction ring crystal face data are consistent with those of ferroferric oxide.
11. The measurement results of the hydration diameter of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 1, example 2, example 3, and example 4 are shown in fig. 11, which are measured by dynamic light scattering. The result shows that the particle sizes of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters with different gadolinium contents are similar.
12. The measurement results of the hydration diameter of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 3 are shown in fig. 12, which are obtained by performing dynamic light scattering measurement on the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters in NaCl solutions with different concentrations. The result shows that the gadolinium-doped magnetic iron oxide nanoclusters can stably exist in salt solutions with different concentrations, and have good biocompatibility.
13. The water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 3 were subjected to a long-term dynamic light scattering measurement and a Zeta potential test, and the results are shown in fig. 13. The result shows that the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster does not generate an agglomeration phenomenon after being placed for a long time, and has good colloidal stability.
14. The hysteresis loops of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 1, example 2, example 3, and example 4 were measured using VSM, and the results thereof are shown in fig. 14. The result shows that the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster has superparamagnetism, and the magnetic saturation intensity is between 50 emu/g and 78 emu/g.
15. Fig. 15 is a graph of the relaxation rate of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 3. The results show that the longitudinal relaxation rate r thereof1Is 28.11mM-1s-1Transverse relaxation rate r2859.7mM-1s-1Can be used as a good contrast agent for magnetic resonance imaging.
16. Fig. 16 is a cell activity diagram of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 3 in THP-1 cells. The result shows that the nanocluster has good biocompatibility and no cytotoxicity.
17. Fig. 17 is an MRI image of the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanoclusters prepared in example 3 in an experimental mouse. The results show that, after nanocluster injection, T is present in the liver of mice1The image becomes brighter gradually, T2The image becomes progressively darker. Therefore, the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster can be used as a contrast agent for magnetic resonance imaging.
Claims (10)
1. A water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster is characterized in that the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster is a secondary structure with the size of 50-200 nanometers and comprises primary structure nanoparticles with the size of 2-10 nanometers and biocompatible macromolecules coated on the surfaces of the primary structure nanoparticles; the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster is prepared from iron oleate, gadolinium oleate and a biocompatible polymer, wherein the mass ratio of the gadolinium oleate to the iron oleate to the biocompatible polymer is 0.1-0.5: 1: 2-10.
2. The water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster according to claim 1, wherein the amount ratio of said gadolinium oleate, iron oleate and biocompatible polymer substance is 0.2:1: 3.
3. The water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster according to claim 1, wherein the biocompatible polymer is selected from polyethylene glycol, carboxyl-terminated polyethylene glycol, methoxypolyethylene glycol, carboxylated methoxypolyethylene glycol or branched polyethylene glycol, and has a number average molecular weight of 400-50000.
4. The method of preparing a water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster of claim 1, comprising the steps of:
a. gadolinium oleate, iron oleate and biocompatible polymer are added into the phenyl ether;
b. heating the reaction solution to 100-120 ℃ in a nitrogen atmosphere, keeping the temperature for 0.5-2 hours, continuously heating to 200 ℃ under the stirring condition, keeping the temperature for 0.5-1 hour, then continuously heating to 259 ℃, and reacting for 0.5-12 hours;
c. and after the reaction liquid is cooled, adding a solvent for washing, centrifuging and drying to obtain the water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster.
5. The method according to claim 4, wherein the ratio of gadolinium oleate, iron oleate and biocompatible polymer in step a is 0.1-0.5: 1: 2-10.
6. The method according to claim 5, wherein the ratio of gadolinium oleate, iron oleate and biocompatible polymer in step a is 0.2:1: 3.
7. The preparation method according to claim 4, wherein the biocompatible polymer in step a is selected from polyethylene glycol, carboxyl-terminated polyethylene glycol, methoxy polyethylene glycol, carboxylated methoxy polyethylene glycol or branched polyethylene glycol, and has a number average molecular weight of 400-50000.
8. The method according to claim 4, wherein the stirring speed in step b is: 400-1000 rpm.
9. The method according to claim 4, wherein the solvent in step c is selected from one or more of ethanol, diethyl ether, acetone, petroleum ether, ethyl acetate, and hexane.
10. Use of the water-soluble biocompatible gadolinium doped magnetic iron oxide nanoclusters of claim 1 as a contrast agent in magnetic resonance imaging.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911136194.7A CN111110870B (en) | 2019-11-19 | 2019-11-19 | Water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911136194.7A CN111110870B (en) | 2019-11-19 | 2019-11-19 | Water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111110870A true CN111110870A (en) | 2020-05-08 |
| CN111110870B CN111110870B (en) | 2022-09-20 |
Family
ID=70495838
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911136194.7A Active CN111110870B (en) | 2019-11-19 | 2019-11-19 | Water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111110870B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112043682A (en) * | 2020-09-19 | 2020-12-08 | 新乡医学院 | Magnetic nano-drug carrier based on porous gadolinium-doped iron oxide nanocluster and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105936820A (en) * | 2016-04-20 | 2016-09-14 | 北京工商大学 | Water soluble biocompatible fluorescent magnetic nanoclusters and preparation method thereof |
-
2019
- 2019-11-19 CN CN201911136194.7A patent/CN111110870B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105936820A (en) * | 2016-04-20 | 2016-09-14 | 北京工商大学 | Water soluble biocompatible fluorescent magnetic nanoclusters and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| PEI-SHIN JIANG等: "Gadolinium-doped iron oxide nanoparticles induced magnetic field hyperthermia combined with radiotherapy increases tumour response by vascular disruption and improved oxygenation", 《INTERNATIONAL JOURNAL OF HYPERTHERMIA》 * |
| YUANCHUN SI等: "Nanostructure-enhanced water interaction to increase the dual-mode MR contrast performance of gadolinium-doped iron oxide nanoclusters", 《CHEMICAL ENGINEERING JOURNAL》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112043682A (en) * | 2020-09-19 | 2020-12-08 | 新乡医学院 | Magnetic nano-drug carrier based on porous gadolinium-doped iron oxide nanocluster and preparation method thereof |
| CN112043682B (en) * | 2020-09-19 | 2022-03-11 | 新乡医学院 | Magnetic nano-drug carrier based on porous gadolinium-doped iron oxide nanocluster and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111110870B (en) | 2022-09-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Casula et al. | Manganese doped-iron oxide nanoparticle clusters and their potential as agents for magnetic resonance imaging and hyperthermia | |
| Bohara et al. | One-step synthesis of uniform and biocompatible amine functionalized cobalt ferrite nanoparticles: a potential carrier for biomedical applications | |
| Baldi et al. | Cobalt ferrite nanoparticles: The control of the particle size and surface state and their effects on magnetic properties | |
| Ge et al. | One‐step synthesis of highly water‐soluble magnetite colloidal nanocrystals | |
| Tan et al. | Synthesis of PEOlated Fe3O4@ SiO2 nanoparticles via bioinspired silification for magnetic resonance imaging | |
| Wang et al. | Superparamagnetic hyperbranched polyglycerol‐grafted Fe3O4 nanoparticles as a novel magnetic resonance imaging contrast agent: an in vitro assessment | |
| Liu et al. | Preparation and characterization of hydrophobic superparamagnetic magnetite gel | |
| Amiri et al. | Superparamagnetic colloidal nanocrystal clusters coated with polyethylene glycol fumarate: a possible novel theranostic agent | |
| Dong et al. | Highly porous, water‐soluble, superparamagnetic, and biocompatible magnetite nanocrystal clusters for targeted drug delivery | |
| Lickmichand et al. | In vitro biocompatibility and hyperthermia studies on synthesized cobalt ferrite nanoparticles encapsulated with polyethylene glycol for biomedical applications | |
| Yang et al. | Monodisperse water-soluble Fe–Ni nanoparticles for magnetic resonance imaging | |
| Zhu et al. | Fluorescent magnetic Fe3O4/rare earth colloidal nanoparticles for dual‐modality imaging | |
| Feng et al. | Synthesis of monodisperse magnetite nanoparticles via chitosan–poly (acrylic acid) template and their application in MRI | |
| Tancredi et al. | Polymer-assisted size control of water-dispersible iron oxide nanoparticles in range between 15 and 100 nm | |
| Katagiri et al. | Development and Potential Theranostic Applications of a Self‐Assembled Hybrid of Magnetic Nanoparticle Clusters with Polysaccharide Nanogels | |
| da Silva et al. | Direct synthesis of magnetite nanoparticles from iron (II) carboxymethylcellulose and their performance as NMR contrast agents | |
| Lu et al. | Sodium polyacrylate modified Fe3O4 magnetic microspheres formed by self-assembly of nanocrystals and their applications | |
| Viali et al. | PEGylation of SPIONs by polycondensation reactions: a new strategy to improve colloidal stability in biological media | |
| Faaliyan et al. | Magnetite-silica nanoparticles with core-shell structure: Single-step synthesis, characterization and magnetic behavior | |
| Yang et al. | Synthesis and characterization of poly (lactic acid)-modified superparamagnetic iron oxide nanoparticles | |
| Lin et al. | Size and morphological effect of Au–Fe 3 O 4 heterostructures on magnetic resonance imaging | |
| Yuan et al. | A novel approach to fabrication of superparamagnetite hollow silica/magnetic composite spheres | |
| CN111110870B (en) | Water-soluble biocompatible gadolinium-doped magnetic iron oxide nanocluster and preparation method and application thereof | |
| Mansur et al. | Synthesis and characterization of iron oxide superparticles with various polymers | |
| King et al. | Exploring precision polymers to fine-tune magnetic resonance imaging properties of iron oxide nanoparticles |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |