CN109529060A - Magnetic composite nano material and its preparation method and application - Google Patents
Magnetic composite nano material and its preparation method and application Download PDFInfo
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- 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
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Abstract
The present invention relates to a kind of magnetic composite nano materials and its preparation method and application.It specifically, is core the invention discloses a kind of metal-doped Ferrite Material, the mesoporous material of acid response is the nanocomposite of shell.The magnetic nanometer composite material can be theoretical based on magnetic resonance harmony, Contrast-enhanced MRI T1Weighted imaging effect.By the magnetic nanometer composite material, applied to can get in magnetic resonance imaging, a kind of imaging performance is significantly excellent, sensitivity to acid is high and T1Its identification and detection to major diseases such as tumours can be improved in signal high-quality MRI contrast agent abundant, to significantly reduce the error and treatment cost of medical image detection.
Description
Technical field
The present invention relates to Material Fields, more particularly to a kind of mesoporous nucleocapsid composite nano materials and preparation method thereof and answer
With.
Background technique
Tumor microenvironment is interior environment locating for tumour, is " soil " that tumour cell is depended on for existence, in the generation of tumour
And play the role of in progression vital.Tumor microenvironment is mainly by stroma cell, capilary, extracellular matrix, phase
The composition such as cell factor, hormone and a small amount of infiltrating cells is closed, is a complicated integrated system, cooperates with and make between each factor
With adjusting the processes such as proliferation, invasion, migration, adherency, the angiogenesis of tumour.
Oxygen molecule is the essential component that intracellular biological energy is maintained during aerobic metabolism, body is many organic and nothing
It can be used as electron acceptor in machine reaction.The abnormal change of oxygen concentration would generally cause metabolic disorder, cause to include apoplexy, tissue
The occurrence and development of a variety of pathologic conditions such as ischemic, inflammation and solid tumor anoxic.Tumor hypoxia refers to the oxygen inside entity tumor
Press subnormal partial pressure of oxygen.The partial pressure of oxygen of most mammalian tissues be 2% -9% (average out to 400mmHg), partial pressure of oxygen≤
2% is defined as anoxia state.Partial pressure of oxygen≤2% when organizing slight anoxia state, partial pressure of oxygen≤0.02% when severe anoxia state,
Tumour growth is rapid, needs to consume a large amount of oxygen and nutriment in growth course, with constantly becoming larger for gross tumor volume, tumour
The speed of growth of blood vessel tends not to meet the rapid growth of the tumor for the needs of oxygen and nutriment, blood supply insufficiency occurs,
Lead to the weary oxygen of inside tumor.Tumor hypoxia can be divided into acute anoxia and chronic hypoxia according to Crack cause.Acute anoxia is mainly
Due to the structure of tumor-microvessel, dysfunction, causes blood perfusion abnormal, oxygen is caused to go out to the transmission process of tumour cell
It is now abnormal.Tumour is under anoxia state, and obstacle occurs for tricarboxylic acid cycle in tumour cell metabolic process, then carries out anaerobic sugar more
Glycolysis discharges a large amount of lactic acid.Meanwhile weary oxygen region tumor tissues peripheral vascular system is not perfect, metabolite cannot be arranged in time
It removes, so that tumor hypoxia region pH value reduces.
Due to safety non-toxic, good biocompatibility (containing a large amount of ferro elements in human body) and stronger MRI radiography
Enhance signal (superparamagnetism of ferric oxide nano particles), ferric oxide nano particles, which have surmounted gadolinium class compound, becomes research most
The MRI radiography material of heat.However, common ferric oxide nano particles are not appropriate for as MRI T1 contrast agent: MRI T1 radiography
Agent should have higher longitudinal relaxation rate (r1) and lower lateral longitudinal relaxation rate ratio (r2/r1≤3), highlight MRI T1 couple
Than effect (maximization).Therefore, it if constructing a kind of safe and non-toxic based on iron-based class nano material (internal indispensable element), makes
The strong MRI T1 radiography material of shadow signal, had not only been able to maintain the safety of contrast medium material, but also can be with the side of MRI T1 weighted imaging
Formula improves diagnosis efficiency, is a kind of highly effective approach, and very necessary.
It is a kind of new theory based on T1 weighted imaging apart from relevant magnetic resonance harmony theory, composition has paramagnetism
" enhancer " and superparamagnetism " quenching son ", when the distance between " enhancer " and " quenching " is less than critical distance, MRI
T1 weighted imaging be it is dark, when the distance between " enhancer " and " quenching son " is greater than critical distance, MRI T1 weighted imaging effect
Fruit can brighten.It can be used as a kind of new sensing principle apart from relevant magnetic resonance harmony theory.Expand extensive biosystem
Exploration.
Apart from relevant magnetic resonance harmony theory have extensive clinical application directive function, it be capable of providing it is faster,
More accurately imaging efficiency.Therefore, it is the diagnosis efficiency for improving the major diseases such as tumour, reduces toxic side effect, it is necessary to develop
A kind of good water solubility, radiography function is strong, has specific expressed MRI contrast agent material to tumor microenvironment.
Summary of the invention
To solve the above problems, it is an object of the present invention to provide a kind of magnetic resonance imaging (MRI) to compare agent material,
The contrast medium material water dissolution properties are good, bio-toxicity is low, degradable under the slightly sour environment of tumour, therefore have and improve the great diseases such as tumour
Sick diagnosis efficiency, the ability for reducing toxic side effect.
Another object of the present invention is to provide a kind of Environmental Safety, simple process, at low cost there is above-mentioned superiority
The life of the tumor region T1 weighting contrasting effects enhancing of the preparation method and slightly sour environment specific detection of the material of energy contrast medium
Object application.
The comparison agent material is the nucleocapsid knot for being enclosed with the mesoporous silicate of magnetic metal doped ferric oxide nano material
Structure.
One aspect of the present invention, provides a kind of magnetic composite nano material, and the magnetic composite nano material has
The following group feature: the magnetic composite nano material includes metal-doped ferrite nano material and the cladding metal-doped iron oxygen
The mesoporous material of body nano material.
In a preferred embodiment, the average grain diameter of the magnetic composite nano material is 40 to 60nm.
In a preferred embodiment, the magnetic composite nano material water or 0.9% physiological saline in disperse 90-
At 270 days, preferably 270-540 days when, at more preferably 360-720 days, the potential change of the magnetic nanometer composite material≤
15%, preferably≤10%, more preferably≤5%, most preferably≤3%.
In a preferred embodiment, based on the total number of the magnetic composite nano material, 70% magnetism is multiple
The partial size of nano material is closed within the scope of the D50 of ± 20% magnetic composite nano material.
In another preferred embodiment, based on the total number of the magnetic composite nano material, 80% (preferably
85%, more preferably 90%, the partial size of the magnetic composite nano material most preferably 93%) be located at ± 15% (preferably ±
10%, more preferably ± 8%) within the scope of the D50 of the magnetic composite nano material.
In a preferred embodiment, the magnetic composite nano material is water-soluble, and oil components are in the magnetism
Content≤0.1wt% of composite nano materials, preferably≤0.05wt%.
In a preferred embodiment, the mesoporous material is mesoporous silicate material.
In another preferred embodiment, the mesoporous material be Metaporous silicon dioxide material, mesoporous silicic acid manganese material,
At least one of the mesoporous silicon of gadolinium ion doping.
In a preferred embodiment, the chemical general formula of the metal-doped ferrite nano material is MxFe3-xO4, wherein
M is selected from least one of Zn, Co and Ni, and X indicates metal-doped concentration range, 0 x≤0.4 <.
In a preferred embodiment, the partial size of the metal-doped ferrite nano material is 4 to 15nm.Another excellent
It selects in embodiment, it is more preferably 9- that the partial size of the magnetic composite nano material, which is 9-15nm, preferably 12-15nm,
10nm is most preferably 10-12nm.
In a preferred embodiment, based on the total number of the metal-doped ferrite nano material, 70% it is described
The partial size of metal-doped ferrite nano material is located at the D50 range of ± 20% metal-doped ferrite nano material
It is interior.
In another preferred embodiment, based on the total number of the magnetic nanometer composite material, 80% (preferably
85%, more preferably 90%, the partial size of the magnetic nanometer composite material most preferably 93%) be located at ± 15% (preferably ±
10%, more preferably ± 8%) within the scope of the D50 of the magnetic nanometer composite material.
In a preferred embodiment, T1Weighted signal strength measures with the following method: stepping magnetic using 0.5T knob
The instrument that resonates measures the T of sample solution1The gray value of weighted imaging is the T1Weighted signal strength.
Another aspect of the present invention provides the method for preparing above-mentioned metal-doped ferrite nano material, the method
It at least includes the following steps:
A) the solution a containing ferro element Fe or containing ferro element and doped metallic elements M is prepared；
B) preparing pH is 10~12 solution b containing oleic acid；
C) solution a is added in solution b, is mixed to get reaction precursor liquid solution c；
D) the reaction precursor liquid solution c is heated to obtain the metal-doped ferrite nano material.
In a preferred embodiment, the doped metallic elements M is selected from least one of Zn, Co and Ni.
In a preferred embodiment, the pH of the solution b is adjusted to by least one of NaOH, KOH and ammonium hydroxide
PH10~12；
In the application, in the preparation process of step a) metal salt precursor solution a, the amount of weighing of metal-doped precursor salt
It can change in a certain range, those skilled in the art can require according to specific, select suitable doping metals salting liquid
Ratio.
Preferably, the molar ratio of step a) the iron oxygen presoma and doping metals salting liquid presoma is not less than 7:1.Into
The preferred range of one step is that the molar ratio of the iron oxygen presoma and doping metals salting liquid presoma is 8:5~32:5.
In a preferred embodiment, stirring is included the steps that in step a), the mixing time is 1-6min, preferably
For 4-6min, more preferably 1-3min.
In a preferred embodiment, the step a) molysite is hydrate.
In a preferred embodiment, the step a) molysite is selected from the group: six aqueous ferrous sulfate ammoniums.
In a preferred embodiment, the step a) doped metal salt is hydrate.
In a preferred embodiment, the step a) doped metal salt is selected from the group: Zinc vitriol, four water sulfuric acid
Manganese, cobalt sulfate, nickel sulfate hexahydrate etc..
In a preferred embodiment, the molten of step b) includes oleic acid and ethyl alcohol, and the volume ratio of the oleic acid and ethyl alcohol is
1:1。
In a preferred embodiment, the mixing time of the step b) stirring be 5-10min, preferably 8-10min, more
Preferably 5-7min.
In a preferred embodiment, the mixing time of the step c) stirring be 3-10min, preferably 8-10min, more
Preferably 3-5min is further preferably 5-7min.
In a preferred embodiment, the mixing in step c) carries out at room temperature.
In a preferred embodiment, the mixing temperature of solution a described in step c) and solution b is 20-30 DEG C, further
Preferred range is 22-26 DEG C.
In a preferred embodiment, step d) summarizes progress in reaction kettle, and the reaction kettle filler is 20-33ml, into
The preferred range of one step is 28-30ml.Preferably, it before precursor solution c is put into reaction kettle, pours into polytetrafluoroethylene (PTFE)
Lining.
In a preferred embodiment, the reaction time described in step d) is 15-20h, further preferred range 18-
20h。
Another aspect of the present invention, provides the method for preparing magnetic composite nano material, the method include at least with
Lower step:
1) high molecular material is dissolved in organic solvent and mesoporous material is added and obtain solution d；
2) solution d is mixed with the organic solution of the metal-doped ferrite nano material, obtains solution e；
3) water is added in Xiang Suoshu solution e, ultrasonic mixing obtains solution f；
4) the heated reaction of solution f is to get the magnetic composite nano material.
In a preferred embodiment, the mesoporous material is selected from mesoporous silicon oxide, mesoporous manganous silicate, gadolinium ion doping
At least one of mesoporous silicon.
In a preferred embodiment, high molecular material described in step 1) include: cetyl trimethylammonium bromide and
Hexadecyltrimethylammonium chloride.
In a preferred embodiment, the amount that organic solvent described in step 1) is added is 1-10ml, and preferred range is
1-5ml, preferred range are 2-3ml.
In a preferred embodiment, step 1) can also include the steps that ultrasonic dissolution, the time of the solution d ultrasound
For 5-15min, preferred range is 5-12min, and preferred range is 9-10min.
In a preferred embodiment, in step 2), the addition quality of high molecular material is that metal-doped ferrite is received
3-6 times of the addition quality of rice material, preferred multiple range is 3-4 times, and preferred multiple range is 5-6 times.
In a preferred embodiment, the organic solvent in step 2) can be chloroform, hexamethylene etc..
In a preferred embodiment, the amount that organic solvent described in step 2) is added is 1-5ml, and preferred range is
2-3ml。
In a preferred embodiment, step 2) can also include using ethyl alcohol, deionized water or combinations thereof as detergent
The step of washing metal-doped ferrite nano material.
In a preferred embodiment, the washing times in step 2) are 3-10 times, further preferred range 5-8
It is secondary.
In a preferred embodiment, the diameter of nano material described in step 2) is 4-15nm, preferred partial size
Range is 4-13nm, and preferred range is 9-13nm.
In a preferred embodiment, the mass concentration of the step 2) nano material is 1-5mg/ml, preferably 1-
3mg/ml, more preferably 1-2mg/ml.
In a preferred embodiment, the time of solution e ultrasound described in step 3) is 5-15min, preferred range
It is 5-12min, further preferred range is 9-10min.
In a preferred embodiment, the step 4) heating temperature range set is 60-80 DEG C, preferably 70-
80 DEG C, more preferably 60-70 DEG C.
In a preferred embodiment, the heating method in step 4) is heating water bath.
In a preferred embodiment, the velocity interval that set mixing speed is reacted in water-bath described in step 4) is
300-600rpm, preferred 300-400rpm, preferred 500-600rpm.
In a preferred embodiment, reaction described in step 4) to solution becomes time range used in brownish clear and is
15-60 minutes, the preferred reaction time was 30-40 minutes.
In a preferred embodiment, the yield of the magnetic composite nano material of the step 4) polymer overmold >=
90%, preferably >=93%, more preferably >=95%.
It is core it is yet another aspect of the present invention to provide a kind of metal-doped iron oxide, mesoporous silicon oxide is the preparation side of shell
Method, the above-mentioned step A of the method) to step D), also at least include the following steps:
In zinc doping oxidation water solution A) a certain amount of NaOH to be added to a certain amount of phase inversion after, it is heated to certain temperature
Degree；
B) when temperature reaches, a certain amount of tetraethyl orthosilicate and ethyl acetate are sequentially added, heated constant temperature is stirred to react
Certain time；
C) after completion of the reaction, ethyl alcohol is added and stops reaction, product is collected by centrifugation and is repeatedly washed with ethyl alcohol and ultrapure water；
D) final product is dissolved in ultrapure water and saving.
In a preferred embodiment, step A) in NaOH concentration range be 1-3M, preferably 2-3M, more preferably
It is 2-2.3M.
In a preferred embodiment, step A) in NaOH additional amount range be 200-400 μ l, preferably 200-
300 μ l, more preferably 200-220 μ l.
In a preferred embodiment, step A) in zinc doping oxidation water solution additional amount range be 40-60ml, it is excellent
Choosing is 40-55ml, more preferably 50-55ml.
In preferred embodiment, step A) heating temperature range set is 60-80 DEG C, preferably 70-80
DEG C, more preferably 70-75 DEG C.
In a preferred embodiment, step A) in heating method be oil bath heating.
In a preferred embodiment, step B) in tetraethyl orthosilicate additional amount range be 50-250 μ l, preferably
50-150 μ l, more preferably 100-110 μ l.
In a preferred embodiment, step B) in ethyl acetate additional amount range be 2-5ml, preferably 3-4ml,
More preferably 3-3.5ml.
In a preferred embodiment, step B) in heating method be oil bath heating.
In preferred embodiment, step B) heating temperature range set is 60-80 DEG C, preferably 70-80
DEG C, more preferably 70-75 DEG C.
In a preferred embodiment, step B) in the range of heating time be 2-4h, preferably 2-3h, more preferably
Be 2.5-3h.
In a preferred embodiment, step C) in centrifugal rotational speed range be 10000-13000rpm, preferably
11000-13000rpm, more preferably 12500-13000rpm.
In a preferred embodiment, step C) in centrifugation time range be 8-20min, preferably 8-15min, more
Preferably 10-12min.
It is the preparation method of mesoporous manganous silicate it is yet another aspect of the present invention to provide a kind of reaction of mesoporous silicon oxide shell,
The above-mentioned step I) of the method is also at least included the following steps to step IV):
I) by a certain amount of MnSO4·H2O and the dissolution mixing of Malaysia acid disodium, obtain solution g；
II) taking a certain amount of metal-doped iron oxide is core, and mesoporous silicon oxide is dissolved in molten for the composite nanoparticle of shell
Ultrasonic mixing uniformly obtains solution h in liquid g；
III) solution h is transferred in the liner of polytetrafluoroethylene (PTFE), high temperature and pressure heating reaction certain time；
IV) final product is collected by centrifugation and uses ethyl alcohol and water washing several times, to remove residue.
In a preferred embodiment, step I) in MnSO4·H2The range of the additional amount of O is 8-80mg, preferably 8-
40mg, more preferably 8-16mg.
In a preferred embodiment, step I) in Malaysia acid disodium additional amount range be 10-100mg, preferably
It is 10-50mg, more preferably 10-20mg.
In preferred embodiment, step II) volume range of the solution g is 10-30ml, preferably 10-20ml,
More preferably 15-20ml.
In a preferred embodiment, heating method described in step III) is baking oven heating.
In a preferred embodiment, range of reaction temperature described in step III) is 140-180 DEG C, preferably 160-
180 DEG C, preferred 170-180 DEG C.
In a preferred embodiment, reaction time range described in step III) is 5-30min, preferably 5-
15min, preferred 8-10min.
In a preferred embodiment, the range of the centrifugal rotational speed in step IV) is 10000-13000rpm, preferably
11000-13000rpm, more preferably 12500-13000rpm.
In a preferred embodiment, the centrifugation time range in step IV) be 8-20min, preferably 8-15min,
More preferably 10-12min.
Another aspect of the present invention provides above-mentioned magnetic composite nano material, is answered according to the magnetism of above method preparation
Nano material is closed to prepare MRI radiography material, preparing tumor microenvironment diagnostic materials, separation cell and as in pharmaceutical carrier
At least one application.
Another aspect of the invention, provides a kind of magnetic resonance imaging contrast agent, and the magnetic resonance imaging contrast agent includes
Above-mentioned magnetic composite nano material, the magnetic composite nano material prepared according to the above method.
By system research of the invention, a kind of superparamagnetic metal haveing excellent performance is obtained by using solvent-thermal method and is mixed
Miscellaneous ferrite radiography material.Specifically, core-shell structure can be formed by coating mesoporous silica, single step reaction of going forward side by side, which generates, to be situated between
Hole manganous silicate, is prepared that a kind of particle size range is concentrated, stability is good, water dispersible is good, toxicity is low, tumor region reduction of contrast signal
(especially T1Weighted signal) the high and higher MRI radiography material of yield.The preparation method of the radiography material has environmental protection peace
Entirely, the compound MRI radiography material is applied to obtain in magnetic resonance imaging by simple process, feature at low cost and high yield
A kind of imaging performance specificity is excellent, slightly sour environment-responsive high RST high-quality MRI contrast agent abundant, improve to tumour etc.
The discovery and detection of major disease, and then medicine detection and treatment cost are significantly reduced, this has guarantee people's life and health
There is important meaning.On this basis, inventor completes the present invention.
Term
As used herein, term " metal-doped ferrite nano material ", refers to the nano material with the following group feature:
1) relaxation rate r2≥325.0mM-1s-1；
2) relaxation rate ratio r2/r1 >=13.
As used herein, term " magnetic composite nanoparticles " refer in the outer of the metal-doped ferrite nano material
Composite material is formed by after surface cladding nanosphere or macromolecule.
As used herein, term " TEOS " is the abbreviation of tetraethyl orthosilicate.
As used herein, term " CTAB " is the abbreviation of cetyl trimethylammonium bromide.
As used herein, term " CTAC " is the abbreviation of hexadecyltrimethylammonium chloride.
As used herein, term " MRI " is the abbreviation of magnetic resonance imaging.
As used herein, term " room temperature " refers to 0-30 DEG C, preferably 4-25 DEG C.
Magnetic composite nano material
In the prior art, with Fe3O4It is used for the ferrite nano material of representative generally as MRI T2 contrast medium, example
Such as marketed products Contrast agents (Feridex) and the Portugal Tie Suo amine (Resovist).However T2 class contrast medium belongs to dark signal function
Enhancing contrast medium (tumor focus region is shown as black/dark, and normal surrounding tissue is shown as white/bright), such contrast medium institute
The focal areas such as tumour, the cardiovascular and cerebrovascular disease (atherosclerotic plaque) of label be easy with certain special areas (such as bleeding,
Calcification or metal deposit) mutually obscure；Simultaneously because such contrast medium magnetic moment is higher, easily induces the fluctuation of local magnetic field and cause
Part marked region is excessively exaggerated, and there is a possibility that image is fuzzy, in clinical diagnosis referred to as " flowering efiect "；Therefore, it aoxidizes
There is no the T1 contrast medium of the class containing gadolinium is high for the degree of recognition of the imaging identification of iron T2 class contrast medium in clinical application.
But, it is contemplated that the essential element " Fe " of superparamagnetic iron oxide nano material is human essential elements, biofacies
The far super T1 radiography containing " gadolinium " class of the application effect of capacitive and safety clinically, while superparamagnetic iron oxide nano material
Also clinically used as the iron supplementary of human body.Therefore, develop one kind can either high selection, enhance tumor region with sensitivity
The bright signal of MRI T1, while replacing but also with the radiography medicament of higher clinical use safety and higher radiography timeliness ability
For existing gadolinium class contrast medium, early diagnosis and prognosis evaluation for malignant tumour, cardio-cerebrovascular diseases are all had important
Scientific meaning and social (economy) value.
Exactly on this basis, the present inventor designs and is prepared for a kind of tumor microenvironment based on magnetic resonance harmony theory
The significant magnetic resonance contrast agent of MRI T1 signal.
The present invention is by having the mesoporous of responsiveness to acidic environment in the surface of magnetic composite nano material cladding
Manganous silicate can significantly increase the biocompatibility of the magnetic composite nano material and reduce its toxicity (especially when it uses agent
When measuring larger).
The beneficial effect that the application can generate includes:
(1) the magnetic composite nano material has uniform particle diameter and distribution concentration, crystallinity height, superparamagnetism, MRI are speeded
Henan has excellent performance, T1The significant and safe and non-toxic feature of reduction of contrast signal；
(2) effective control to the magnetic composite nano scantling can be realized by the reaction time；
(3) it can realize have to the composite magnetic composite nano materials partial size by the thickness of control mesoporous material shell
Effect control, and then adjust its target different organs (such as nano material partial size be less than 10nm when, or can by blood-brain barrier into
Enter brain；When nano material partial size is 10nm-30nm, it can stay in the long period in blood to be used as blood pool contrast medium；It receives
Rice material particle size be 30nm-150nm when, can intravascular enter multiple organs such as conscience spleen kidney；Nano material partial size is 150-
When 250nm, it can be swallowed by the reticuloendothelial cell of liver；Nano material of the partial size greater than 1 μm can be retained by Pulmonary Vascular
Deng)；
(4) the magnetic composite nano material and/or the core-shell nano composite material can be used for preparing MRI radiography material
Material, tumor disease targeted drug, tumor disease diagnostic materials and/or pharmaceutical carrier, and separation cell etc.；
(5) compared to T used in clinic1Contrast medium Gd coordination compound class preparation, the magnetic composite nano material and/or institute
Core-shell nano composite material is stated as T1There is stronger tumour T1 radiography specificity, and its bio-toxicity is far below when contrast medium
Gd coordination compound class preparation is a kind of very excellent lesion detection type T1Radiography material.
Detailed description of the invention
Fig. 1 is a kind of embodiment preparation process schematic diagram of the application.
Fig. 2 shows TEM as a result, wherein Fig. 2 (a) is 2 gained Zn of embodiment0.2Fe2.8O4The TEM of nanoparticle is as a result, Fig. 2
It (b) is 8 gained Zn of embodiment0.2Fe2.8O4@mSiO4The TEM of core-shell structure nanometer particle is as a result, Fig. 2 (c) is 10 gained of embodiment
Zn0.2Fe2.8O4@MnSiO4The TEM of core-shell structure nanometer particle is as a result, Fig. 2 (d) is Zn0.2Fe2.8O4@MnSiO4Nano combined material
Material is in lower 2 days Electronic Speculum results of PBS (pH=6.5).
Fig. 3 is 2 gained Zn of embodiment0.2Fe2.8O4The XRD result of nanoparticle.
Fig. 4 is 2 gained Zn of embodiment0.2Fe2.8O4The VSM result of nanoparticle.
Fig. 5 is 10 gained Zn of embodiment0.2Fe2.8O4@MnSiO4The dynamic particle size distribution tests of core-shell structure nanometer particle.
Fig. 6 is 10 gained Zn of embodiment0.2Fe2.8O4@MnSiO4The Zeta potential of core-shell structure nanometer particle is tested.
Fig. 7 is 10 gained Zn of embodiment0.2Fe2.8O4@MnSiO4The external MRI of the acid-sensitive of core-shell structure nanometer particle is special
Property test.
Fig. 8 is 11 gained Zn of embodiment0.2Fe2.8O4@MnSiO4The MCF-7 cell of@IR780 core-shell structure nanometer particle is total
It is incubated for 2h and is copolymerized burnt picture.
Fig. 9 is 10 gained Zn of embodiment0.2Fe2.8O4@MnSiO4The MCF-7 cytotoxicity test of core-shell structure nanometer particle.
Figure 10 is 10 gained Zn of embodiment0.2Fe2.8O4@MnSiO4The tumor bearing nude mice MRI of core-shell structure nanometer particle is tested.
Specific embodiment
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In the following examples, the experimental methods for specific conditions are not specified, usually according to conventional strip
Part or according to the normal condition proposed by manufacturer.Unless otherwise stated, otherwise percentage and number are calculated by weight.
Unless otherwise defined, it anticipates known to all professional and scientific terms as used herein and one skilled in the art
Justice is identical.In addition, any method similar to or equal to what is recorded and material can be applied to the method for the present invention.Wen Zhong
The preferred implement methods and materials are for illustrative purposes only.
A kind of embodiment according to the present invention, the inventive concept of preparation process mainly include that synthesis obtains as shown in Figure 1:
Partial size pattern is uniform, good crystallinity zinc doping ferrite nano particles, simultaneously because can control the reaction time to control
The partial size of iron oxide material.
Universal testing method
Water dispersible test
Test equipment: Malvern Nano-ZS type dynamic light scattering particle size instrument, test condition: angle of scattering 173o.
Particle diameter distribution test
Test equipment: Malvern Nano-ZS type dynamic light scattering particle size instrument, test condition: angle of scattering 173o.
XRD
Test equipment: Brueckner D8Advance X-ray diffractometer；Test condition: Cu K α target (40kV, 40mA),
0.02 ° of step-length (2 θ), 3s/ step.
TEM
Test equipment: JEOL-2100 type transmission electron microscope；Test condition: 200Kv, 101 μ A；And nanoparticle to be measured
Son, which is dispersed in water, to be tested.
The measurement of MRI relaxation rate
Test equipment: MesoMR23-060H-I nuclear magnetic resonance spectroscopy and imaging system；Test condition is T1: TR=
200ms, TE=20ms, T2: TR=2000ms, TE=20ms.
The T of MRI1Weighted imaging
Test equipment: MesoMR23-060H-I nuclear magnetic resonance spectroscopy and imaging system；Test condition is T1: TR=
200ms, TE=20ms,
The T of MRI2Weighted imaging
Test equipment: MesoMR23-060H-I nuclear magnetic resonance spectroscopy and imaging system；Test condition is T2: TR=
2000ms, TE=20ms.
1 sample 1 of embodiment#Preparation
(1) 1gNaOH is weighed in 100ml beaker, 10ml oleic acid and 10ml ethyl alcohol is added thereto, in magnetic stirring apparatus
Upper stirring to NaOH dissolution is uniformly dispersed, and obtains solution a；
(2) 1.73mM Fe is weighed2+Salt and 0.267mM Zn2+Salt is dissolved in 20ml ultrapure water, and ultrasound is all molten to salt
Solution is uniformly mixed, and obtains solution b；
(3) under room temperature, it is added drop-wise in solution a in above-mentioned solution b, magnetic agitation to solution becomes brown clarification and is
Only, solution c is obtained；
(4) it takes 30ml c solution to be transferred in polytetrafluoroethylliner liner, and is put into reaction kettle and seals, reaction kettle is put into
In baking oven, 230 DEG C of isothermal reaction 20h；
(5) after completion of the reaction, reaction kettle is cooled to room temperature, and the nanoparticle chloroform of polytetrafluoroethylliner liner bottom is molten
Solution is taken out into 50ml centrifuge tube, and excess ethyl alcohol is added into centrifuge tube, and 8000rpm centrifuge washing 5 times, obtained final production
Object Zn0.1Fe2.9O4Nano material is denoted as sample 1#, it is dissolved in chloroform, 4 DEG C of preservations.
As a result
Respectively to 1 gained Zn of embodiment0.1Fe2.9O4Nano material carry out TEM, particle diameter distribution test, ICP-OES, XRD,
VSM, MRI relaxation rate measurement imaging, T1 and T2 weighted imaging of MRI etc. detect.
2 sample 2 of embodiment#Preparation
(1) 1gNaOH is weighed in 100ml beaker, 10ml oleic acid and 10ml ethyl alcohol is added thereto, in magnetic stirring apparatus
Upper stirring to NaOH dissolution is uniformly dispersed, and obtains solution a；
(2) 1.73mM Fe is weighed2+Salt and 0.534mM Zn2+Salt is dissolved in 20ml ultrapure water, and ultrasound is all molten to salt
Solution is uniformly mixed, and obtains solution b；
(3) under room temperature, it is added drop-wise in solution a in above-mentioned solution b, magnetic agitation to solution becomes brown clarification and is
Only, solution c is obtained；
(4) 30ml solution c is transferred in polytetrafluoroethylliner liner, and is put into reaction kettle and seals, reaction kettle is put into
In baking oven, 230 DEG C of isothermal reaction 20h；
(5) after completion of the reaction, reaction kettle is cooled to room temperature, and the nanoparticle chloroform of polytetrafluoroethylliner liner bottom is molten
Solution is taken out into 50ml centrifuge tube, and excess ethyl alcohol is added into centrifuge tube, and 8000rpm centrifuge washing 6 times, obtained final production
Object Zn0.2Fe2.8O4Nano material is denoted as sample 2#, it is dissolved in chloroform, 4 DEG C of preservations.
As a result
Respectively to 2 gained Zn of embodiment0.2Fe2.8O4Nano material carry out TEM, particle diameter distribution test, ICP-OES, XRD,
VSM, MRI relaxation rate measurement imaging, T1 and T2 weighted imaging of MRI etc. detect, wherein gained Zn0.2Fe2.8O4Nanoparticle
VSM result is as shown in Figure 4.
3 sample 3 of embodiment#Preparation
(1) 1gNaOH is weighed in 100ml beaker, 10ml oleic acid and 10ml ethyl alcohol is added thereto, in magnetic stirring apparatus
Upper stirring to NaOH dissolution is uniformly dispersed, and obtains solution a；
(2) 1.73mM Fe is weighed2+Salt and 0.801mM Zn2+Salt is dissolved in 20ml ultrapure water, and ultrasound is all molten to salt
Solution is uniformly mixed, and obtains solution b；
(3) under room temperature, it is added drop-wise in solution a in above-mentioned solution b, magnetic agitation to solution becomes brown clarification and is
Only, solution c is obtained；
(4) 30ml solution c is transferred in polytetrafluoroethylliner liner, and is put into reaction kettle and seals, reaction kettle is put into
In baking oven, 230 DEG C of isothermal reaction 20h；
(5) after completion of the reaction, reaction kettle is cooled to room temperature, and the nanoparticle chloroform of polytetrafluoroethylliner liner bottom is molten
Solution is taken out into 50ml centrifuge tube, and excess ethyl alcohol is added into centrifuge tube, and 8000rpm centrifuge washing 8 times, obtained final production
Object Zn0.3Fe2.7O4Nano material is denoted as sample 3#, it is dissolved in chloroform, 4 DEG C of preservations.
As a result
Respectively to 3 gained Zn of embodiment0.3Fe2.7O4Nano material carry out TEM, particle diameter distribution test, ICP-OES, XRD,
VSM, MRI relaxation rate measurement imaging, T1 and T2 weighted imaging of MRI etc. detect.
4 sample 4 of embodiment#Preparation
(1) 1gNaOH is weighed in 100ml beaker, 10ml oleic acid and 10ml ethyl alcohol is added thereto, in magnetic stirring apparatus
Upper stirring to NaOH dissolution is uniformly dispersed, and obtains solution a；
(2) 1.73mM Fe is weighed2+Salt and 1.068mM Zn2+Salt is dissolved in 20ml ultrapure water, and ultrasound is all molten to salt
Solution is uniformly mixed, and obtains solution b；
(3) under room temperature, it is added drop-wise in solution a in above-mentioned solution b, magnetic agitation to solution becomes brown clarification and is
Only, solution c is obtained；
(4) 30ml solution c is transferred in polytetrafluoroethylliner liner, and is put into reaction kettle and seals, reaction kettle is put into
In baking oven, 230 DEG C of isothermal reaction 20h；
(5) after completion of the reaction, reaction kettle is cooled to room temperature, and the nanoparticle chloroform of polytetrafluoroethylliner liner bottom is molten
Solution is taken out into 50ml centrifuge tube, and excess ethyl alcohol is added into centrifuge tube, and 8000rpm centrifuge washing 8 times, obtained final production
Object Zn0.4Fe2.6O4Nano material is denoted as sample 4#, it is dissolved in chloroform, 4 DEG C of preservations.
As a result
Respectively to 4 gained Zn of embodiment0.4Fe2.6O4Nano material carry out TEM, particle diameter distribution test, ICP-OES, XRD,
VSM, MRI relaxation rate measurement imaging, T1 and T2 weighted imaging of MRI etc. detect.
5 sample 5 of embodiment#Preparation
(1) 1gNaOH is weighed in 100ml beaker, 10ml oleic acid and 10ml ethyl alcohol is added thereto, in magnetic stirring apparatus
Upper stirring to NaOH dissolution is uniformly dispersed, and obtains solution a；
(2) 1.73mM Fe is weighed2+Salt and 0.534mM Co2+Salt is dissolved in 20ml ultrapure water, and ultrasound is all molten to salt
Solution is uniformly mixed, and obtains solution b；
(3) under room temperature, it is added drop-wise in solution a in above-mentioned solution b, magnetic agitation to solution becomes brown clarification and is
Only, solution c is obtained；
(4) 30ml solution c is transferred in polytetrafluoroethylliner liner, and is put into reaction kettle and seals, reaction kettle is put into
In baking oven, 230 DEG C of isothermal reaction 20h；
(5) after completion of the reaction, reaction kettle is cooled to room temperature, and the nanoparticle chloroform of polytetrafluoroethylliner liner bottom is molten
Solution is taken out into 50ml centrifuge tube, and excess ethyl alcohol is added into centrifuge tube, and 8000rpm centrifuge washing 5-8 times, what is obtained is final
Product Co0.2Fe2.8O4Nano material is denoted as sample 5#, it is dissolved in chloroform, 4 DEG C of preservations.
As a result
5 gained Co of embodiment0.2Fe2.8O4Nano material carries out TEM, particle diameter distribution test, ICP-OES, XRD, VSM, MRI
Relaxation rate measures the T of imaging, MRI1And T2The detection such as weighted imaging.
6 sample 6 of embodiment#Preparation
(1) 1gNaOH is weighed in 100ml beaker, 10ml oleic acid and 10ml ethyl alcohol is added thereto, in magnetic stirring apparatus
Upper stirring to NaOH dissolution is uniformly dispersed, and obtains solution a；
(2) 1.73mM Fe is weighed2+Salt and 0.534mM Ni2+Salt is dissolved in 20ml ultrapure water, and ultrasound is all molten to salt
Solution is uniformly mixed, and obtains solution b；
(3) under room temperature, it is added drop-wise in solution a in above-mentioned solution b, magnetic agitation to solution becomes brown clarification and is
Only, solution c is obtained；
(4) it takes 30ml c solution to be transferred in polytetrafluoroethylliner liner, and is put into reaction kettle and seals, reaction kettle is put into
In baking oven, 230 DEG C of isothermal reaction 20h；
(5) after completion of the reaction, reaction kettle is cooled to room temperature, and the nanoparticle chloroform of polytetrafluoroethylliner liner bottom is molten
Solution is taken out into 50ml centrifuge tube, and excess ethyl alcohol is added into centrifuge tube, and 8000rpm centrifuge washing 8 times, obtained final production
Object Ni0.2Fe2.8O4Nano material is denoted as sample 6#, it is dissolved in chloroform, 4 DEG C of preservations.
As a result
6 gained Ni of embodiment0.2Fe2.8O4Nano material carries out TEM, particle diameter distribution test, ICP-OES, XRD, VSM, MRI
Relaxation rate measures the T of imaging, MRI1And T2The detection such as weighted imaging.
7 sample 7 of embodiment#Preparation
(1) 1gNaOH is weighed in 100ml beaker, 10ml oleic acid and 10ml ethyl alcohol is added thereto, in magnetic stirring apparatus
Upper stirring to NaOH dissolution is uniformly dispersed, and obtains solution a；
(2) 1.73mM Fe is weighed2+Salt and 0.534mM Mn2+Salt is dissolved in 20ml ultrapure water, and ultrasound is all molten to salt
Solution is uniformly mixed, and obtains solution b；
(3) under room temperature, it is added drop-wise in solution a in above-mentioned solution b, magnetic agitation to solution becomes brown clarification and is
Only, solution c is obtained；
(4) it takes 30ml c solution to be transferred in polytetrafluoroethylliner liner, and is put into reaction kettle and seals, reaction kettle is put into
In baking oven, 230 DEG C of isothermal reaction 20h；
(5) after completion of the reaction, reaction kettle is cooled to room temperature, and the nanoparticle chloroform of polytetrafluoroethylliner liner bottom is molten
Solution is taken out into 50ml centrifuge tube, and excess ethyl alcohol is added into centrifuge tube, and 8000rpm centrifuge washing 8 times, obtained final production
Object Mn0.2Fe2.8O4Nano material is denoted as sample 7#, it is dissolved in chloroform, 4 DEG C of preservations.
As a result
7 gained Mn of embodiment0.2Fe2.8O4Nano material carries out TEM, particle diameter distribution test, ICP-OES, XRD, VSM, MRI
Relaxation rate measures the T of imaging, MRI1And T2The detection such as weighted imaging.
8 sample 8 of embodiment#Preparation
(1) it weighs 0.3g CTAC to be dissolved in 10ml chloroform, 1ml (Fe2+0.7mg/ml) is taken to be dissolved in the nanoparticle of chloroform
Ultrasonic 10min；
(2) 20ml ultrapure water, ultrasonic 20min is added；
(3) 60 DEG C of oil bath heated at constant temperature stirrings remove chloroforms to solution turned clear；
(4) it is settled to 50ml, is gone in three-necked flask, 300 μ l 2M NaOH are added, when continuing to be heated to 70 DEG C,
100 μ l TEOS, 3ml ethyl acetate are sequentially added, 3h is stirred to react；
(5) at the end of the reaction time, ethyl alcohol is added, and reaction was completed, and 13000rpm revolving speed is collected by centrifugation and uses ethanol washing 3
It is secondary, milli-Q water 5 times, obtained final product Zn0.2Fe2.8O4@mSiO2Nano material is dissolved in ultrapure water, is denoted as sample
8#。
As a result
8 gained Zn of embodiment0.2Fe2.8O4@mSiO2Nano material carries out TEM (shown in Fig. 2 (b)), particle diameter distribution is tested,
ICP-OES, XRD, VSM test.
9 sample 9 of embodiment#Preparation
(1) it weighs 0.3g CTAB to be dissolved in 10ml chloroform, 1ml (Fe2+0.7mg/ml) is taken to be dissolved in the nanoparticle of chloroform
Ultrasonic 10min；
(2) 20ml ultrapure water, ultrasonic 20min is added；
(3) 60 DEG C of oil bath heated at constant temperature stirrings remove chloroforms to solution turned clear；
(4) it is settled to 50ml, is gone in three-necked flask, 300 μ l 2M NaOH are added, when continuing to be heated to 70 DEG C,
100 μ l TEOS, 3ml ethyl acetate are sequentially added, 3h is stirred to react；
(5) at the end of the reaction time, ethyl alcohol is added, and reaction was completed, is collected by centrifugation and with ethanol washing 3 times, milli-Q water
5 times, obtained final product Zn0.2Fe2.8O4@mSiO2Nano material is denoted as sample 9#。
As a result
9 gained Zn of embodiment0.2Fe2.8O4@mSiO2Nano material carry out TEM, particle diameter distribution test, ICP-OES, XRD,
VSM test.
10 sample 10 of embodiment#Preparation
(1) MnSO is weighed4·H2O (8mg) and Malaysia acid disodium (10mg) mixing are dissolved in 10ml ultrapure water；
(2) Zn is taken0.2Fe2.8O4@mSiO2Nano material sample 8#Solution 10ml, by the mixed solution of (1) step in ultrasound
Under conditions of be added drop-wise in nano-particle solution dropwise；
(3) 20ml mixed solution is transferred in 50ml reaction kettle, under hydrothermal conditions 180 DEG C of 10min；
(4) it is collected by centrifugation and with ethanol washing 3 times and water washing 5 times, to remove residue, obtained final product is denoted as
Sample 10#。
11 sample 11 of embodiment#Preparation
(1) IR780 dyestuff (2.5mg) is weighed to be dissolved in 500 μ l ethyl alcohol；
(2) 5mg Zn is taken0.2Fe2.8O4@mSiO2Nano material sample 8#It is dissolved in 500 μ l ethyl alcohol, by the solution of (1) step
It is mixed with, ultrasonic 1h；
(3) it is collected by centrifugation, and washes extra IR780 dyestuff with ethyl alcohol；
(4) final product is denoted as sample 11#It is dissolved in PBS buffer solution and saving.
12 sample 1 of embodiment#~11#Transmission electron microscope analysis result
Transmission electron microscope is respectively adopted to sample 1#~11#It is analyzed, as the result is shown: magnetic composite nano material
The partial size of material is 40 between 60nm, and the partial size of the 70% magnetic composite nano material is located at ± 20% magnetic
Within the scope of the D50 of property composite nano materials.
With sample 2#(Zn0.2Fe2.8O4Nanoparticle), sample 8#(Zn0.2Fe2.8O4@mSiO4Core-shell structure nanometer particle),
Sample 10#(Zn0.2Fe2.8O4@MnSiO4Core-shell structure nanometer particle) it is Typical Representative, TEM photo is respectively such as Fig. 2 (a), Fig. 2
(b), shown in Fig. 2 (c).By Fig. 2 (a) it can be seen that Zn0.2Fe2.8O4Nanoparticle pattern uniform particle sizes, particle size is in 10nm
Left and right；Fig. 2 (b) can be seen that the kernel external sheath mesoporous silicon oxide shell of one layer of 8-10nm thickness.It is shown in Fig. 2 (b)
On the basis of by meso-porous titanium dioxide pasc reaction be mesoporous manganous silicate, pattern partial size do not change significantly.
Fig. 2 (d) is sample 10#(Zn0.2Fe2.8O4@MnSiO4Core-shell structure nanometer particle) lower 2 days in PBS (pH=6.5)
Electronic Speculum as a result, being compared with Fig. 2 (c) as can be seen that standing 2 days in the PBS (pH=6.5) after, sample does not have significant change.
13 sample 1 of embodiment#~7#Material phase analysis result
Transmission electron microscope is respectively adopted to sample 1#~7#It is analyzed, as the result is shown: sample 1#~7#It all has
Crystal phase structure.
Typical Representative such as sample 2#(Zn0.2Fe2.8O4Nanoparticle), XRD diagram is as shown in figure 3, as seen from the figure, XRD
Data show, Zn0.2Fe2.8O4Nanoparticle belongs to inverse spinel structure.
14 sample 1 of embodiment#~7#Vibrating specimen magnetometer analyze result
1#-4#The saturation magnetization changing rule of sample: when increasing to 0.2 with zinc doping concentration, saturation magnetization
Increase to maximum value, but when zinc doping concentration continues growing, saturation magnetization starts to reduce, in which:
Zn0.1Fe2.9O4:60emu/g；
Zn0.2Fe2.8O4:66emu/g；
Zn0.3Fe2.7O4:48emu/g；
Zn0.4Fe2.6O4:43emu/g.
15 sample 8 of embodiment#~11#Dynamic particle size analyze result
Through analyzing, 8#-11#Dynamic particle size in 44nm or so, do not change significantly.Wherein sample 10#Core-shell structure
The dynamic particle size distribution tests result of nanoparticle is as shown in Figure 5.
16 sample 8 of embodiment#~11#Zeta potential test result
Potential test the results show that 8#-11#Zeta potential all in -30mV or so.Wherein sample 10#Core-shell structure is received
Test results are shown in figure 6 for the Zeta potential of rice corpuscles.
17 sample 10 of embodiment#With 11#The external MRI specific test result of acid-sensitive
In vitro in the test of MRI T1 weighted imaging, sample places 50min under the conditions of PBS (pH=6.5), with control group
Comparing under the conditions of PBS (pH=7.4), it can be seen that the sample of PBS (pH=6.5) obviously brightens, and illustrates that material has
There is acid-sensitive to respond effect.Wherein, sample 10#The external MRI specific test result of the acid-sensitive of core-shell structure nanometer particle is such as
Shown in Fig. 7.
18 sample 10 of embodiment#With 11#MCF-7 cytotoxicity test results
Toxotest can be seen that material in the concentration range of 0-300 mcg/ml, and cell survival rate is higher, all protects
It holds 90% or more.Illustrate that Materials Cell toxicity is low.Wherein, sample 11#Zn0.2Fe2.8O4@MnSiO4@IR780 core-shell structure is received
The copolymerization coke picture that the MCF-7 cell of rice corpuscles is incubated for 2h altogether is as shown in Figure 8.Sample 10#Gained Zn0.2Fe2.8O4@MnSiO4Core
The MCF-7 cytotoxicity test results of shell structural nano particle is as shown in Figure 9.
19 sample 10 of embodiment#With 11#Tumor bearing nude mice MRI test result
Tumor region be in subacidity, material tail vein injection enter carry out being recycled into tumour in Mice Body when, certain
Under action time, it can be seen that tumor region brightens compared with blank group, illustrates that material acid responds internal T1 weighted imaging enhancing
Effect is good.Wherein, sample 10#Gained Zn0.2Fe2.8O4@MnSiO4The tumor bearing nude mice MRI test result of core-shell structure nanometer particle
As shown in Figure 10.
The above is only several embodiments of the application, not does any type of limitation to the application, although this Shen
Please disclosed as above with preferred embodiment, however not to limit the application, any person skilled in the art is not taking off
In the range of technical scheme, a little variation or modification are made using the technology contents of the disclosure above and is equal to
Case study on implementation is imitated, is belonged in technical proposal scope.
Claims (10)
1. a kind of magnetic composite nano material, which is characterized in that the magnetic composite nano material includes metal-doped ferrite
Nano material and the mesoporous material for coating the metal-doped ferrite nano material.
2. magnetic composite nano material according to claim 1, which is characterized in that the magnetic composite nano material is put down
Equal partial size is 40 to 60nm；
Preferably, the magnetic composite nano material water or 0.9% physiological saline in stable dispersion, potential change≤
15%；
Preferably, based on the total number of the magnetic composite nano material, the partial size of the 70% magnetic composite nano material
Within the scope of the D50 of ± 20% magnetic composite nano material；
Preferably, the magnetic composite nano material is water-soluble, and oil components contain the magnetic composite nano material
Amount≤0.1wt%.
3. magnetic composite nano material according to claim 1, which is characterized in that the mesoporous material is mesoporous silicate
Material；
Preferably, the mesoporous material be Metaporous silicon dioxide material, mesoporous silicic acid manganese material, gadolinium ion doping mesoporous silicon in
At least one.
4. magnetic composite nano material according to claim 1, which is characterized in that the metal-doped ferrite nano material
The chemical general formula of material is MxFe3-xO4, wherein M is selected from least one of Zn, Co and Ni, and X indicates metal-doped concentration range, and 0
X≤0.4 <；
Preferably, the partial size of the metal-doped ferrite nano material is 4 to 15nm；
Preferably, based on the total number of the metal-doped ferrite nano material, the 70% metal-doped ferrite is received
The partial size of rice material is within the scope of the D50 of ± 20% metal-doped ferrite nano material.
5. the method for preparing metal-doped ferrite nano material described in claim 1, which is characterized in that the method is at least wrapped
Include following steps:
A) the solution a containing ferro element Fe or containing ferro element and doped metallic elements M is prepared；
B) preparing pH is 10~12 solution b containing oleic acid；
C) solution a is added in solution b, is mixed to get reaction precursor liquid solution c；
D) the reaction precursor liquid solution c is heated to obtain the metal-doped ferrite nano material.
6. according to the method described in claim 5, it is characterized in that, the doped metallic elements M in Zn, Co and Ni extremely
Few one kind.
7. the method for preparing the described in any item magnetic composite nano materials of Claims 1-4, which is characterized in that the method
It at least includes the following steps:
1) high molecular material is dissolved in organic solvent and mesoporous material is added and obtain solution d；
2) solution d is mixed with the organic solution of the metal-doped ferrite nano material, obtains solution e；
3) water is added in Xiang Suoshu solution e, ultrasonic mixing obtains solution f；
4) the heated reaction of solution f is to get the magnetic composite nano material.
8. the method according to the description of claim 7 is characterized in that the mesoporous material is selected from mesoporous silicon oxide, mesoporous silicon
At least one of sour manganese, mesoporous silicon of gadolinium ion doping.
9. the described in any item magnetic composite nano materials of Claims 1-4 are prepared according to claim 7 or 8 the methods
Magnetic composite nano material is preparing MRI radiography material, is preparing tumor microenvironment diagnostic materials, separation cell and as drug load
The application of at least one of body.
10. a kind of magnetic resonance imaging contrast agent, which is characterized in that the magnetic resonance imaging contrast agent includes according to claim 1
To 4 described in any item magnetic composite nano materials, the magnetic composite nano material prepared according to claim 7 or 8 the methods
Material.
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| CN113730574A (en) * | 2020-05-29 | 2021-12-03 | 中国科学院宁波工业技术研究院慈溪生物医学工程研究所 | Composite nano material, preparation method and application |
| CN114053966A (en) * | 2021-03-04 | 2022-02-18 | 中国科学院宁波材料技术与工程研究所 | Hydrophilic magnetic nano material and preparation method and application thereof |
| US11779652B2 (en) | 2021-06-18 | 2023-10-10 | Imam Abdulrahman Bin Faisal University | Porous silicate/magnetic ferrite nanocarrier for combination anti-cancer therapeutic and antioxidant delivery |
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