CN108439487A - A kind of magnetic nano-particle and preparation method thereof can be used for cancer target magnetic therapy - Google Patents
A kind of magnetic nano-particle and preparation method thereof can be used for cancer target magnetic therapy Download PDFInfo
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- CN108439487A CN108439487A CN201810355387.0A CN201810355387A CN108439487A CN 108439487 A CN108439487 A CN 108439487A CN 201810355387 A CN201810355387 A CN 201810355387A CN 108439487 A CN108439487 A CN 108439487A
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- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
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- C01G51/00—Compounds of cobalt
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
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- C01G49/00—Compounds of iron
- C01G49/0018—Mixed oxides or hydroxides
- C01G49/0072—Mixed oxides or hydroxides containing manganese
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- C01G53/00—Compounds of nickel
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- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/01—Particle morphology depicted by an image
- C01P2004/04—Particle morphology depicted by an image obtained by TEM, STEM, STM or AFM
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- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/80—Particles consisting of a mixture of two or more inorganic phases
- C01P2004/82—Particles consisting of a mixture of two or more inorganic phases two phases having the same anion, e.g. both oxidic phases
- C01P2004/84—Particles consisting of a mixture of two or more inorganic phases two phases having the same anion, e.g. both oxidic phases one phase coated with the other
Abstract
The invention belongs to medical nanometer structured field of functional materials, and in particular to a kind of magnetic nano-particle and preparation method thereof can be used for cancer target magnetic therapy.The magnetic nano-particle, which is reacted by divalent transition metal salt with divalent and/or trivalent iron salt, to be combined, molecular formula MxFe3‑xO4, x=0.15 0.45, M Mn2+、Ni2+Or Co2+.The present invention breaks through the Traditional Thinking of synthesis ferroso-ferric oxide, and a certain proportion of transition metal salt is adulterated in molysite and ferrous salt, and magnetism M is generated by coprecipitation methodxFe3‑xO4Nano-particle.Magnetic nano-particle heat production effect under externally-applied magnetic field is preferable, optical fiber temperature-measurement records 15 minutes effectively temperature and rises 14 DEG C, the magnetic nano-particle is used for experiment in vitro, part of macrophages can effectively be killed, the thus great potentiality for cancer target heat cure are expected to solve the drawbacks of long-term administration caused by body to injuring.
Description
Technical field
The invention belongs to medical nanometer structured field of functional materials, and in particular to a kind of magnetic can be used for cancer target magnetic therapy
Property nano-particle and preparation method thereof.
Background technology
The treatment of malignant tumour is a global problem all the time.The non-operative treatment of tumour includes radiotherapy and change
It treats, for the purpose of killing tumour cell, but above-mentioned therapy lacks the spy to tumour cell
Even there is the tolerance to radiotherapy, chemotherapy in the opposite sex, some tumour cells, and health refers to after this causes patient to treat
Mark degradation.
In recent years, with the raising of Protocols in Molecular Biology, and from the molecular level pair of cell receptor and multiplication regulatory
The further understanding of Tumorigenesis, people proceed by controlling using cell receptor, key gene and regulatory molecule as target spot
It treats, also referred to as target treatment.However, the adverse reaction that targeted drug is used for a long time can not be ignored, targeted drug is taken for a long time,
It will necessarily influence normal adjusting function, it may appear that a variety of undesirable reactions.Therefore, it is that have very much must to probe into new targeted therapies
It wants.
Magnetic particle obtains extensively in terms of the biological medicines such as targeting magnetic therapy and target administration, cell separation and immunoassay
Application.Using magnetisable material as targeting vector, the research one that magnetic medicinal preparations is made is combined with drug and high molecular material
It is directly one of most active field of current medical new formulation., can be under outer introduction by magnetic field after said preparation injects lesions position, medicine
Object timing, positioning, constant speed, quantitative release play the maximum effect of drug and reduce side effect.But above-mentioned traditional magnetic
Property particle targeted therapy still do not overcome prolonged administration of drugs to be influenced caused by the normal adjusting function of body.
Invention content
To solve the above problems, the present invention provides a kind of magnetic nano-particle can be used for cancer target magnetic therapy and its preparation
Method.The present invention prepares four oxygen of superparamagnetic nanometer of monodispersity with divalent transition metal salt and divalent and/or trivalent iron salt
Change three-iron compound particle, a kind of magnetic can be used for specificity, efficient cancer target magnetic therapy that collaboration targeting proteins synthesize
Property nano-particle.Constantly reverse generates heat to the magnetic nano-particle of the targeting under the action of alternating magnetic field, to
Kill cancer cell can be oriented.The successful implementation of the present invention provides new exploration thinking for the treatment of malignant tumour, has weight
The clinical value wanted and potential social benefit.
To achieve the above object, the present invention uses following technical scheme：
One of the object of the invention provides a kind of magnetic nano-particle, and the magnetic nano-particle is by divalent transition metal salt
It reacts and is combined with divalent and/or trivalent iron salt, molecular formula MxFe3-xO4, x=0.15-0.45, M Mn2+、Ni2+Or Co2 +。
The two of the object of the invention provide a kind of preparation method of magnetic Nano ion, include the following steps：(1) press mole
Than 1:0.1-0.4:0.1-0.4 weighs trivalent iron salt, divalent iron salt and divalent transition metal salt respectively, and distilled water, stirring is added
And it is heated to 80 DEG C three kinds of compounds is made fully to dissolve obtaining homogeneous mixed solution；
(2) ammonium hydroxide is added into above-mentioned steps (1) mixed solution, until solution ph is 10,80 DEG C of constant temperature continues to stir 1h
Afterwards, it is slowly dropped to room temperature, reaction product is detached with external magnet and rinsed to pH value as 7 to get M with deionized waterxFe3-xO4；
(3) M that step (2) is preparedxFe3-xO4Coated with silica, Carboxylation processing or amination modification are carried out,
To obtain the final product；The divalent transition metal salt divalent transition metal salt is MnCl2·4H2O、NiSO4·6H2O or CoCl2·6H2O；Institute
It is FeCl to state divalent iron salt2·4H2O、FeSO4·7H2O or Fe (NO3)2；The trivalent iron salt is FeCl3·6H2O、Fe2
(SO4)3·9H2O or Fe (NO3)3。
The three of the object of the invention provide the magnetic nano-particle in preparing the nano-particle for cancer target magnetic therapy
Application.
The four of the object of the invention provide a kind of magnetic nano-particle for cancer target magnetic therapy, by described above magnetic
Nano-particle MxFe3-xO4Covalent coupling effect occurs with targeting proteins to be made.
The five of the object of the invention provide the magnetic nano-particle preparation method for being used for cancer target magnetic therapy, will be above-mentioned
Magnetic nano-particle is thoroughly dispersed in 1 × DPBS buffer solutions of 10 volumes, is diluted to the final concentration of 10mg/ of nano-particle
ml；Take 80 μ l above-mentioned solution EDC room temperatures activation 30min, be then added the targeting proteins 1 of the 20 final concentration of 1mg/ml of μ l ×
DPBS solution is incubated at room temperature 1 hour.
Beneficial effects of the present invention are：
In majority is studied, the superparamagnetism of magnetic nano-particle is usually emphasized, but seldom nationwide examination for graduation qualification is observed its heat production
Performance is used for magnetic field therapy.The present invention breaks through the Traditional Thinking of synthesis ferroso-ferric oxide, is adulterated in molysite and ferrous salt certain
The transition metal salt (such as salt compounds of manganese, cobalt, nickel) of ratio generates magnetism M by coprecipitation methodxFe3-xO4Nanometer
Particle.Magnetic nano-particle heat production effect under externally-applied magnetic field is preferable, and optical fiber temperature-measurement records 15 minutes effectively temperature and rises 1-4 DEG C,
The magnetic nano-particle is used for experiment in vitro, can effectively kill part of macrophages, thus great for cancer target heat cure
Potentiality, be expected to solve long-term administration to being injured caused by body the drawbacks of.
Description of the drawings
The accompanying drawings which form a part of this application are used for providing further understanding of the present application, and the application's shows
Meaning property embodiment and its explanation do not constitute the improper restriction to the application for explaining the application.
Fig. 1 is the TEM figures of the target magnetic nano particle prepared；
Fig. 2 is thermogenic effects figure of the magnetic nano-particle of preparation in externally-applied magnetic field；
Fig. 3 is the additional alternating magnetic field equipment of experiment；
Fig. 4 be prepare nano-particle combining with green fluorescin after by Macrophage inflammatory protein-1α.
Specific implementation mode
It is noted that described further below be all exemplary, it is intended to provide further instruction to the present invention.Unless another
It indicates, all technical and scientific terms used herein has usual with general technical staff of the technical field of the invention
The identical meanings of understanding.
It should be noted that term used herein above is merely to describe specific implementation mode, and be not intended to restricted root
According to exemplary embodiments of the present invention.As used herein, unless the context clearly indicates otherwise, otherwise singulative
It is also intended to include plural form, additionally, it should be understood that, when in the present specification using term "comprising" and/or " packet
Include " when, indicate existing characteristics, step, operation, component and/or combination thereof.
One of the object of the invention provides a kind of magnetic nano-particle, and the magnetic nano-particle is by divalent transition metal salt
It reacts and is combined with divalent and/or trivalent iron salt, molecular formula MxFe3-xO4, x=0.15-0.45, M Mn2+、Ni2+Or Co2 +。
Further, the divalent transition metal salt divalent transition metal salt is MnCl2·4H2O、NiSO4·6H2O or
CoCl2·6H2O。
Further, the divalent iron salt is FeCl2·4H2O、FeSO4·7H2O or Fe (NO3)2。
Further, the trivalent iron salt is FeCl3·6H2O、Fe2(SO4)3·9H2O or Fe (NO3)3。
The two of the object of the invention provide a kind of preparation method of magnetic Nano ion, include the following steps：(1) press mole
Than 1:0.1-0.4:0.1-0.4 weighs trivalent iron salt, divalent iron salt and divalent transition metal salt respectively, and distilled water, stirring is added
And it is heated to 80 DEG C three kinds of compounds is made fully to dissolve obtaining homogeneous mixed solution；
(2) ammonium hydroxide is added into above-mentioned steps (1) mixed solution, until solution ph is 10,80 DEG C of constant temperature continues to stir 1h
Afterwards, it is slowly dropped to room temperature, reaction product is detached with external magnet and rinsed to pH value as 7 to get M with deionized waterxFe3-xO4；
(3) M that step (2) is preparedxFe3-xO4Coated with silica, Carboxylation processing or amination modification are carried out,
To obtain the final product；The divalent transition metal salt divalent transition metal salt is MnCl2·4H2O、NiSO4·6H2O or CoCl2·6H2O；Institute
It is FeCl to state divalent iron salt2·4H2O、FeSO4·7H2O or Fe (NO3)2；The trivalent iron salt is FeCl3·6H2O、Fe2
(SO4)3·9H2O or Fe (NO3)3。
Further, the step (1) in molar ratio 1:0.25:0.25 weighs trivalent iron salt, divalent iron salt and divalent respectively
Transition metal salt.
Further, the step (1) in molar ratio 1:0.3:0.2 weighs trivalent iron salt, divalent iron salt and divalent mistake respectively
Cross metal salt.
The three of the object of the invention provide the magnetic nano-particle in preparing the nano-particle for cancer target magnetic therapy
Application.
The four of the object of the invention provide a kind of magnetic nano-particle for cancer target magnetic therapy, by described above magnetic
Nano-particle MxFe3-xO4Covalent coupling effect occurs with targeting proteins to be made.
The five of the object of the invention provide the magnetic nano-particle preparation method for being used for cancer target magnetic therapy, by right
It is required that 1 magnetic nano-particle is thoroughly dispersed in 1 × DPBS buffer solutions of 10 volumes, the end for being diluted to nano-particle is dense
Degree is 10mg/ml；The above-mentioned solution EDC room temperatures activation 30min of 80 μ l are taken, the targeting of the 20 final concentration of 1mg/ml of μ l is then added
Albumen 1 × DPBS solution is incubated at room temperature 1 hour.
In conjunction with specific example, the present invention is further illustrated, and following embodiment is merely to explain the present invention, not
Its content is defined.
Embodiment 1
Using coprecipitation, 1.7gFeCl is weighed3·6H2O, 0.32gFeCl2·4H2O, 0.42gNiSO4·6H2O (threes
The ratio between amount of substance is 1:0.25:0.25) it, is put in the four-hole boiling flask of 500ml, 200ml deionized waters is added, stirs evenly and matches
At mixed solution.In N2Under protection, 85~90 DEG C are heated to water-bath, 1.5M is added dropwise dropwise in powerful motor whipping process
Ammonium hydroxide, mixed solution is gradually converted into orange red, is finally changed into black by orange-yellow, while having a large amount of black particle shapes solid
Body generates, and waits for that pH rises to 8~9, and the ammonium hydroxide for being further continued for being added dropwise 10ml 1.5M is allowed to be fully hydrolyzed, and stops stirring and is burnt at three mouthfuls
Bottle lower section place magnet, standing wait for that black powder is sunken to bottom of bottle completely, with pipette remove supernatant liquid, black particle spend from
Sub- water washing 3 times is finally stored in deionized water for use with the concentration of 1mg/ml.
The nanoscale ferroso-ferric oxide about 0.1g prepared in above-mentioned steps is put in the four-hole boiling flask of 500ml, is added
0.6gNa2SiO3·9H2O adds 100ml deionized waters.Powerful motor stirs and is passed through nitrogen protection, is heated with water-bath
To 85-90 DEG C, starts the hydrochloric acid solution that 2M is added dropwise dropwise, the pH of system is adjusted to 6 or so, heating water bath about 60 minutes stops
It only stirs, magnet is placed below four-hole boiling flask, waits for that black powder is all sunken to bottom of bottle, supernatant liquid, black are removed with pipette
Powder is washed with deionized 3 times, can get through SiO2Modified nanoscale ferroso-ferric oxide particle.
It will be prepared in above-mentioned steps through SiO2Modified nanoscale ferroso-ferric oxide particle about 0.1g is put in the four of 500ml
In mouth flask, 90ml absolute ethyl alcohols are measured, 5ml deionized water (volume ratios are added：Absolute ethyl alcohol：Water=18:1) 5ml, is added
KH550 (it is 5% to account for system volume fraction), after hydrolyzing 10min or so in 200ml small beakers, is transferred in four-hole boiling flask,
N2Under protection, about 2.5~3h is reacted under strong stirring.Stop stirring, magnet is placed below four-hole boiling flask, waits for the oxidation of nanometer four three
Iron particle is all sunken to bottom of bottle, removes the clear body in upper layer with pipette, lower black particle alcohol and deionized water are washed respectively
Three times, can obtain KH550 modifications contains-NH3The magnetic nanoparticle of functional group.
- NH is contained using EDC method handles3The magnetic nano-particle of functional group is covalently bound on targeting proteins, specific method
It is as follows：First containing NH3The magnetic nano-particle of functional group is thoroughly dispersed in 1 × DPBS (PBS) buffer solution of 10 volumes
In, it is diluted to the final concentration of 10mg/ml of nano-particle；The above-mentioned solution EDC room temperatures activation 30min of 80 μ l are taken, are then added
1 × DPBS of targeting proteins (PBS) solution of the 20 final concentration of 1mg/ml of μ l is incubated at room temperature 1 hour.The magnetic Nano of preparation
Particle diameter 7nm, saturation magnetic field intensity 30emu/g, particle is placed under additional alternating magnetic field, is recorded with optical fiber temperature-measurement, 15 points
Clock heats up 3.7 DEG C.
Embodiment 2
In molar ratio 1:0.4:0.1 weighs the FeCl of corrresponding quality3·6H2O、FeSO4·7H2O、NiSO4·6H2O, by real
The method for applying example 1 is tested, and the magnetic nano-particle grain size of preparation is respectively 5nm；Saturation magnetic field intensity is respectively 10emu/
Particle is placed under additional alternating magnetic field, is recorded with optical fiber temperature-measurement by g, heats up 1.3 DEG C within 15 minutes.
Embodiment 3
In molar ratio 1:0.3:0.2 weighs the FeCl of corrresponding quality3·6H2O、FeSO4·7H2O、NiSO4·6H2O, by real
The method for applying example 1 is tested, and the magnetic nano-particle grain size of preparation is respectively 20nm；Saturation magnetic field intensity is respectively 30emu/
Particle is placed under additional alternating magnetic field, is recorded with optical fiber temperature-measurement by g, heats up 2.7 DEG C within 15 minutes.
Embodiment 4
In molar ratio 1:0.2:0.3 weighs the FeCl of corrresponding quality3·6H2O、FeSO4·7H2O、NiSO4·6H2O, by real
The method for applying example 1 is tested, and the magnetic nano-particle grain size of preparation is respectively 10nm；Saturation magnetic field intensity is respectively 50emu/
Particle is placed under additional alternating magnetic field, is recorded with optical fiber temperature-measurement by g, heats up 2.2 DEG C within 15 minutes.
Embodiment 5
In molar ratio 1:0.1:0.4 weighs the FeCl of corrresponding quality3·6H2O、FeSO4·7H2O、NiSO4·6H2O, by real
The method for applying example 1 is tested, and the magnetic nano-particle grain size of preparation is respectively 40nm；Saturation magnetic field intensity is respectively 40emu/
Particle is placed under additional alternating magnetic field, is recorded with optical fiber temperature-measurement by g, heats up 1 DEG C within 15 minutes.
Embodiment 6
Using coprecipitation, 1.7gFeCl is weighed3·6H2O, 0.32gFeCl2·4H2O, 0.38gCoCl2·6H2O (threes
The ratio between amount of substance is 1:0.25:0.25) it, is put in the four-hole boiling flask of 500ml, 200ml deionized waters is added, stirs evenly and matches
At mixed solution.In N2Under protection, 85~90 DEG C are heated to water-bath, 1.5M is added dropwise dropwise in powerful motor whipping process
Ammonium hydroxide, mixed solution is gradually converted into orange red, is finally changed into black by orange-yellow, while having a large amount of black particle shapes solid
Body generates, and waits for that pH rises to 8~9, and the ammonium hydroxide for being further continued for being added dropwise 10ml 1.5M is allowed to be fully hydrolyzed, and stops stirring and is burnt at three mouthfuls
Bottle lower section place magnet, standing wait for that black powder is sunken to bottom of bottle completely, with pipette remove supernatant liquid, black particle spend from
Sub- water washing 3 times is finally stored in deionized water for use with the concentration of 1mg/ml.
The nanoscale ferroso-ferric oxide about 0.1g prepared in above-mentioned steps is put in the four-hole boiling flask of 500ml, is added
0.6gNa2SiO3·9H2O adds 100ml deionized waters.Powerful motor stirs and is passed through nitrogen protection, is heated with water-bath
To 85-90 DEG C, starts the hydrochloric acid solution that 2M is added dropwise dropwise, the pH of system is adjusted to 6 or so, heating water bath about 60 minutes stops
It only stirs, magnet is placed below four-hole boiling flask, waits for that black powder is all sunken to bottom of bottle, supernatant liquid, black are removed with pipette
Powder is washed with deionized 3 times, can get through SiO2Modified nanoscale ferroso-ferric oxide particle.
It will be prepared in above-mentioned steps through SiO2Modified nanoscale ferroso-ferric oxide about 0.1g is put into 500ml three-necked flasks
In, add 0.75gNa2CO3And 0.4gClCH2COOH, is eventually adding 100ml deionized waters, and powerful motor stirs and is passed through nitrogen
Gas shielded is heated to 50~60 DEG C with water-bath, reacts about 1~1.5h.Stop stirring, places magnet below three-necked flask, wait for
Black powder is all sunken to bottom of bottle, and supernatant liquid is removed with pipette, and black powder is washed with deionized 3 times, can get
ClCH2COOH modified nanoscale ferroso-ferric oxides containing-COOH functional groups again.
The magnetic nano-particle containing-COOH functional groups is covalently bound on targeting proteins using EDC methods, specific method
It is as follows：1 × DPBS (PBS) bufferings for the magnetic nano-particle containing-COOH functional groups being thoroughly dispersed in first 10 volumes are molten
In liquid, it is diluted to the final concentration of 10mg/ml of nano-particle；The above-mentioned solution EDC room temperatures activation 30min of 80 μ l are taken, are then added
Enter 1 × DPBS of targeting proteins (PBS) solution of the 20 final concentration of 1mg/ml of μ l, is incubated at room temperature 1 hour.The magnetism of preparation is received
Rice corpuscles grain size 20nm, saturation magnetic field intensity 40emu/g, particle is placed under additional alternating magnetic field, is recorded with optical fiber temperature-measurement, and ten
2.3 DEG C of minute heating.
Embodiment 7
In molar ratio 1:0.4:0.1 weighs the FeCl of corrresponding quality3·6H2O、FeSO4·7H2O、CoCl2·6H2O, by real
The method for applying example 2 is tested, and the magnetic nano-particle grain size of preparation is respectively 10nm；Saturation magnetic field intensity is respectively 15emu/
Particle is placed under additional alternating magnetic field, is recorded with optical fiber temperature-measurement by g, heats up 1.7 DEG C within 15 minutes.
Embodiment 8
In molar ratio 1:0.3:0.2 weighs the FeCl of corrresponding quality3·6H2O、FeSO4·7H2O、CoCl2·6H2O, by real
The method for applying example 2 is tested, and the magnetic nano-particle grain size of preparation is respectively 25nm；Saturation magnetic field intensity is respectively 20emu/
Particle is placed under additional alternating magnetic field, is recorded with optical fiber temperature-measurement by g, heats up 2.5 DEG C within 15 minutes.
Embodiment 9
In molar ratio 1:0.2:0.3 weighs the FeCl of corrresponding quality3·6H2O、FeSO4·7H2O、CoCl2·6H2O, by real
The method for applying example 2 is tested, and the magnetic nano-particle grain size of preparation is respectively 10nm；Saturation magnetic field intensity is respectively 30emu/
Particle is placed under additional alternating magnetic field, is recorded with optical fiber temperature-measurement by g, heats up 1.1 DEG C within 15 minutes.
Embodiment 10
In molar ratio 1:0.1:0.4 weighs the FeCl of corrresponding quality3·6H2O、FeSO4·7H2O、CoCl2·6H2O, by real
The method for applying example 2 is tested, and the magnetic nano-particle grain size of preparation is respectively 30nm；Saturation magnetic field intensity is respectively 45emu/
Particle is placed under additional alternating magnetic field, is recorded with optical fiber temperature-measurement by g, heats up 1.5 DEG C within 15 minutes.
Embodiment 11
In order to investigate preparation magnetic nano-particle into cell mechanism, the present invention by embodiment 1 or embodiment 6 side
Method contains-NH being prepared3Or after the magnetic nano-particle of-COOH functional groups, using EDC methods green fluorescent protein
On covalent coupling to chemically modified nano-particle.
It takes appropriate macrophage to be placed in 20mm culture dishes from Tissue Culture Flask points, takes 20ul to combine with liquid-transfering gun green
The nanometer Fe of color fluorescin3O4Be added cell culture fluid in, after stationary incubation 2h, under Laser Scanning Confocal Microscope observe particle into
The process of cell observes and records primary for every five minutes.
The experimental results showed that the magnetic nano-particle of preparation can successfully be swallowed by macrophage, general 48 hours
Left and right can be fully saturated, and experimental result is ideal, and the targeting magnetic field treatment for magnetic nano-particle for tumour is laid
Good basis.
Claims (10)
1. a kind of magnetic nano-particle, which is characterized in that the magnetic nano-particle by divalent transition metal salt and divalent and/or
Trivalent iron salt reaction is combined, molecular formula MxFe3-xO4, x=0.15-0.45, M Mn2+、Ni2+Or Co2+。
2. magnetic nano-particle as described in claim 1, which is characterized in that the divalent transition metal salt divalent transition metal salt
For MnCl2·4H2O、NiSO4·6H2O or CoCl2·6H2O。
3. magnetic nano-particle as described in claim 1, which is characterized in that the divalent iron salt is FeCl2·4H2O、FeSO4·
7H2O or Fe (NO3)2。
4. magnetic Nano ion as described in claim 1, which is characterized in that the trivalent iron salt is FeCl3·6H2O、Fe2
(SO4)3·9H2O or Fe (NO3)3。
5. the preparation method of magnetic Nano ion as described in claim 1, which is characterized in that include the following steps：
(1) in molar ratio 1:0.1-0.4:0.1-0.4 weighs trivalent iron salt, divalent iron salt and divalent transition metal salt respectively, adds
Enter distilled water, is stirred and heated to 80 DEG C three kinds of compounds is made fully to dissolve and obtain homogeneous mixed solution；
(2) ammonium hydroxide is added into above-mentioned steps (1) mixed solution, until solution ph is 10,80 DEG C of constant temperature continues after stirring 1h, delays
Slow to be down to room temperature, reaction product is detached with external magnet and is rinsed to pH value as 7 to get M with deionized waterxFe3-xO4；
(3) M that step (2) is preparedxFe3-xO4Coated with silica, Carboxylation processing or amination modification are carried out, i.e.,
；The divalent transition metal salt divalent transition metal salt is MnCl2·4H2O、NiSO4·6H2O or CoCl2·6H2O；It is described
Divalent iron salt is FeCl2·4H2O、FeSO4·7H2O or Fe (NO3)2；The trivalent iron salt is FeCl3·6H2O、Fe2(SO4)3·
9H2O or Fe (NO3)3。
6. the preparation method of magnetic Nano ion as described in claim 1, which is characterized in that the step (1) is in molar ratio
1:0.25:0.25 weighs trivalent iron salt, divalent iron salt and divalent transition metal salt respectively.
7. the preparation method of magnetic Nano ion as described in claim 1, which is characterized in that the step (1) is in molar ratio
1:0.3:0.2 weighs trivalent iron salt, divalent iron salt and divalent transition metal salt respectively.
8. application of the magnetic nano-particle as described in claim 1 in preparing the nano-particle for cancer target magnetic therapy.
9. a kind of magnetic nano-particle for cancer target magnetic therapy, which is characterized in that the magnetic nano particle described in claim 1
Son occurs covalent coupling effect with targeting proteins and is made.
10. being used for the nano-particle preparation method of cancer target magnetic therapy as claimed in claim 9, which is characterized in that right
It asks 1 magnetic nano-particle to be thoroughly dispersed in 1 × DPBS buffer solutions of 10 volumes, is diluted to the final concentration of nano-particle
For 10mg/ml；The above-mentioned solution EDC room temperatures activation 30min of 80 μ l are taken, the targeting egg of the 20 final concentration of 1mg/ml of μ l is then added
White 1 × DPBS solution is incubated at room temperature 1 hour.
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