CN105288668A - Zinc-doped prussian blue nanoparticle, preparation method and applications thereof - Google Patents
Zinc-doped prussian blue nanoparticle, preparation method and applications thereof Download PDFInfo
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Abstract
The present invention provides a zinc-doped prussian blue nanoparticle preparation method, wherein a hexaoyanoferrous acid substance and zinc methacrylate are adopted as raw materials, an organic acid with a specific concentration is matched to prepare the zinc-doped prussian blue nanoparticles having double bond on the surface, and an organic layer having carboxyl, amino, hydroxyl and other functional groups is modified on the nanoparticle surface through a polymerization reaction. Another purpose of the present invention is to provide the zinc-doped prussian blue nanoparticles prepared through the preparation method, and clinical applications of the zinc-doped prussian blue nanoparticles as the contrast agent in magnetic resonance imaging and photoacoustic bifunctional imaging. According to the present invention, the prepared zinc-doped prussian blue nanoparticles have characteristics of good water solubility, good biocompatibility and good light-heat stability, and amino, carboxyl or hydroxyl and the like are modified on the nanoparticle surface so as to provide favorable conditions for the further surface modification and antibody grafting.
Description
Technical field
The invention belongs to biomedical materials field, prussian blue nano granule being specifically related to a kind of zinc doping and preparation method thereof, and it is as magnetic resonance and the application clinically of the difunctional image-forming contrast medium of optoacoustic.
Background technology
Bio-imaging technology mainly comprises optical imagery, nuclear magnetic resonance, ultra sonic imaging and positron imaging etc.Optical imagery has highly sensitive, and detection time is short, but has the features such as limitation to deep tissues imaging, and nuclear magnetic resonance can carry out deep tissues imaging, but sensitivity is lower, and thus, two kinds of imaging techniques have good mutual supplement with each other's advantages feature.Photoacoustic imaging is a kind of emerging non-invasive imaging technique that development in recent years is got up, and its principle causes thermal expansion after utilizing material absorbing luminous energy and this principle of sound wave produced carries out imaging.The advantages such as relative to other optical image technology, it is higher that photoacoustic imaging has resolution, and penetration depth is larger.Because biological tissue does not significantly absorb near infrared light region, it is darker to penetrating of tissue, so be introduced near infrared region to have the strong photoacoustic imaging contrast agent absorbed to improve the signal to noise ratio of photoacoustic imaging, utilize near-infrared laser can realize carrying out imaging to the tissue of more deep layer as the excitation source of photoacoustic imaging.
Biomedical contrast agents material is paid close attention to widely along with the development of imaging technique and the needs of research and diagnosis obtain.Current magnetic resonance contrast agent mainly comprises gadolinium class contrast agent and ferroso-ferric oxide class contrast agent, gadolinium class contrast agent relaxation rate is lower, use, containing having during gadolinium contrast agent, sexual system Fibrotic risk in kidney source occurs, there is hundreds of routine death, and the internal metabolism problem of ferroso-ferric oxide is not yet resolved, be therefore necessary the magnetic resonance contrast agent of Development of Novel.Photoacoustic contrast agent mainly comprises inorganic nano material and the micromolecule organic dyestuff etc. such as gold nano-material, copper sulfide nano material, graphene nano material.Due to shortcomings such as gold nano-material heat stability are poor, and the biosafety issues of inorganic nano material is not resolved, and micromolecule organic dyestuff is easily affected by environment, and light stability is poor, and circulation time in vivo is short, therefore the photoacoustic contrast agent of Development of Novel is imperative.
Prussian blue is a kind of antidote that be can be used as some heavy metal poisoning for the treatment of of clinical practice by FDA approval, its structure is electron rich cyano group bridging ferric ion and ferrous ion forming surface centered cubic lattice, its shortcoming is water insoluble, thus can not carry out the injection of body angular vein.Existing research confirms the Prussian blue imaging applications as MRI contrast agent (J.Mater.Chem., 2010,20,5251-5259; InorganicChemistryCommunications, 2010,13,58-61; ) and imaging applications (Chem.Commun., 2013,49, the 11029-11031 of photoacoustic contrast agent; Biomaterials, 2014,35,9844-9852.).But, water miscible Prussian blue KFe [Fe (CN)
6] owing to having potassium ion, intravenous injection application has limitation, and Fe
4[Fe (CN)
6]
3water insoluble again.
Therefore a kind of novel type radiographic contrast is developed, can in conjunction with MRI imaging and photoacoustic imaging based on Prussian blue nano-particle, give full play to the advantage of two kinds of imaging techniques, overcome again the inferior position of prussian blue nano granule, for research and clinical diagnosis provide information to be more reliably one of this area problem demanding prompt solution simultaneously.
Summary of the invention
In order to solve the technical problem of above-mentioned existence, the object of the present invention is to provide a kind of preparation method of prussian blue nano granule of zinc doping, the method introduces double bond by doping zinc methacrylate at prussian blue nano particle surface, and superscribes organic layer by polyreaction at the prussian blue nano particle surface of zinc doping.
The present invention also aims to the prussian blue nano granule of the zinc doping providing a kind of above-mentioned preparation method to prepare.
The present invention also aims to provide a kind of prussian blue nano granule of above-mentioned zinc doping as magnetic resonance and the application clinically of the difunctional image-forming contrast medium of optoacoustic.
Object of the present invention is achieved by the following technical programs:
A preparation method for the prussian blue nano granule of zinc doping, comprises the following steps:
Step one: be dissolved in solvent by six cyanogen network ferrum acids, organic acid, after mixing and stirring, be mixed with solution A, wherein contains six cyanogen network ferrum acid 0.002-0.02g, organic acid 0.002-0.02g in every milliliter of solution A;
Step 2: be dissolved in solvent by iron chloride salt, organic acid, after mixing and stirring, be mixed with B solution, wherein contains iron chloride salt 0.002-0.02g, organic acid 0.002-0.02g in every milliliter of B solution;
Step 3: be dissolved in by zinc salt in solvent, after mixing and stirring, is mixed with C solution, wherein contains zinc salt 0.002-0.02g in every milliliter of C solution;
Step 4: C solution magnetic agitation is even, is heated to 60-100 DEG C and the 0.5-3h that refluxes, then adds B solution, mixing and stirring, and then dropwise add solution A, magnetic agitation reaction 0.5-4h, and centrifugalize obtains intermediate product D; Wherein, the mass ratio of solution A and B solution is 1:0.2-1:2, and the mass ratio of B solution and C solution is 1:10-10:1;
Step 5: intermediate product D is dissolved in solvent, be heated to 50-120 DEG C, then initiator is added, magnetic agitation reaction 2-10min, add polymer again, magnetic agitation reaction 0.5-4h, cool to room temperature, adopt deionized water dialysis to purify and obtain the prussian blue nano granule of this zinc doping, wherein the mass ratio of intermediate product D, polymer, initiator is (0.05-0.5): (3-15): (0.02-0.1), as long as the addition of solvent guarantees fully to dissolve intermediate product D.Adopting deionized water to dialyse the product obtained can be water-soluble, and therapeutic medical Prussian blue antidote is water-fast.
In above-mentioned preparation method, preferably, described six cyanogen network ferrum acids can comprise one or more the combination in potassium ferrocyanide, the potassium ferricyanide, sodium ferrocyanide, sodium ferricyanide, ferrous ammonium cyanide and ammonium-cu hexacyanoferrate etc.
In above-mentioned preparation method, preferably, described organic acid can comprise one or more the combination in citric acid, tartaric acid, malic acid, succinic acid and diethyl pentetic acid etc.
In above-mentioned preparation method, preferably, described solvent can comprise ethanol and/or ethylene glycol.
In above-mentioned preparation method, preferably, described iron chloride salt can comprise iron chloride and/or ferrous chloride.
In above-mentioned preparation method, preferably, described zinc salt can be zinc methacrylate.Inner nuclear layer adopts the prussian blue nano granule of zinc doping as light absorption material, and efficiency of light absorption is higher, and stability is better.Zinc and ferrum are all the trace element of needed by human, and two kinds of elements are absorbed with the pay-as-you-go operation mutually restricted in vivo, and without other heavy metal ion, have increased substantially biocompatibility.
In above-mentioned preparation method, preferably, in described step 5, initiator can comprise one or more the combination in azodiisobutyronitrile, azo-bis-iso-dimethyl and 2,2'-Azobis(2,4-dimethylvaleronitrile) etc.
In above-mentioned preparation method, preferably, in described step 5, polymer can comprise one or more the combination in PEG methyl ether methacrylate, PEG methacrylate, O-(2-carboxyethyl) PEG methacrylate, O-(2-carboxyethyl) PEG methyl ether methacrylate, O-(2-amino-ethyl) PEG methacrylate and O-(2-amino-ethyl) PEG methyl ether methacrylate etc.The organic layer with functional groups such as amino, carboxyl or hydroxyls is cross-linked by polyreaction; organic layer has good protective effect to stratum nucleare nano-particle; the nano-particle that surperficial amino, carboxyl or hydroxyl make has good water solublity; can improve the biocompatibility of nano-particle, and the amino on surface, carboxyl or hydroxyl are that further finishing and antibody grafting provide condition.The thickness of organic layer can be regulated by the material concentration of control polyreaction, reaction temperature and response time simultaneously, and react without other by-products, environmental protection, operation is simple.The present invention can avoid in physiological conditions at Prussian blue outer layer covers organic layer, other ion in blood and Prussian bluely to react, and affects the stable of Prussian blue body structure.
Present invention also offers a kind of prussian blue nano granule of the zinc doping utilizing above-mentioned preparation method to prepare.
In the prussian blue nano granule of above-mentioned zinc doping, preferably, the ultraviolet and visible absorption peak of the prussian blue nano granule of described zinc doping is between 710 nanometers to 730 nanometers.
Present invention also offers the prussian blue nano granule of above-mentioned zinc doping as magnetic resonance and the application clinically of the difunctional image-forming contrast medium of optoacoustic.This nano-particle inner nuclear layer is that the prussian blue nano granule of zinc doping can produce magnetic resonance signal and photoacoustic signal, outer layer copolymer organic layer, owing to having the hydrophilic functional groups such as surface carboxyl groups, amino, hydroxyl, adds water solublity and the biocompatibility of prussian blue nano granule.The ultraviolet and visible absorption peak of this nano-particle drops between 710 nanometers to 730 nanometers.This nano-particle can be used as magnetic resonance and the difunctional image-forming contrast medium of optoacoustic, in conjunction with two kinds of imaging advantages, for medical diagnosis provides effective information more comprehensively.
Beneficial effect of the present invention:
(1) nano-particle of the present invention is cross-linked the organic layer with functional groups such as amino, carboxyl or hydroxyls by polyreaction.Organic layer has good protective effect to stratum nucleare nano-particle, surperficial amino, carboxyl or hydroxyl make nano-particle have good water solublity, improve the biocompatibility of nano-particle, the amino on surface, carboxyl or hydroxyl provide condition for further finishing and antibody grafting;
(2) the crosslinked upper organic layer of polyreaction is adopted in nanometer grain preparation method of the present invention, the thickness of organic layer can by controlling the material concentration of polyreaction, and reaction temperature and response time regulate, and react without other by-products, environmental protection, operation is simple;
(3) in the nano-particle prepared of the present invention, the prussian blue nano granule of kernel zinc doping is as light absorption material, and efficiency of light absorption is higher, and stability is better;
(4) in the nano-particle prepared of the present invention, inner nuclear layer is the prussian blue nano granule of zinc doping, zinc and ferrum are all micro elements needed by human, and two kinds of elements are absorbed with the pay-as-you-go operation mutually restricted in vivo, without other heavy metal ion, have increased substantially biocompatibility;
(5) adopt organic acid to control the size of nano-particle in nanometer grain preparation method of the present invention, control procedure is more prone to regulation and control.
Accompanying drawing explanation
Fig. 1 is the UV-vis absorption spectrum figure of the prussian blue nano granule of zinc doping;
Fig. 2 is the photoacoustic signal figure of the prussian blue nano granule of zinc doping;
Fig. 3 is the Prussian blue KFe of commercialization [Fe (CN)
6] photoacoustic signal figure.
Detailed description of the invention
In order to there be understanding clearly to technical characteristic of the present invention, object and beneficial effect, existing following detailed description is carried out to technical scheme of the present invention, but can not be interpreted as to of the present invention can the restriction of practical range.
Embodiment 1
Present embodiments provide a kind of preparation method of prussian blue nano granule of zinc doping, comprise the following steps:
Step one: be dissolved in 50mL ethanol by the 329mg potassium ferricyanide, 400mg citric acid, mixing and stirring, is mixed with solution A;
Step 2: be dissolved in 25mL ethanol by 127mg ferrous chloride, 400mg citric acid, mixing and stirring, is mixed with B solution;
Step 3: be dissolved in by 236mg zinc methacrylate in 25mL ethanol, mixing and stirring, is mixed with C solution;
Step 4: C solution magnetic agitation is even, is heated to 80 DEG C and the 1h that refluxes, then adds B solution, mixing and stirring, and then dropwise add solution A, magnetic agitation reaction 3h, and centrifugalize obtains intermediate product D;
Step 5: intermediate product D is dissolved in 100mL ethanol, be heated to 70 DEG C, then 50mg azodiisobutyronitrile is added, magnetic agitation reaction 5min, add 7.5 milliliters of PEG methyl ether methacrylate again, magnetic agitation reaction 1h, cool to room temperature, adopts deionized water dialysis to purify and obtains the prussian blue nano granule of doping.
Embodiment 2
Present embodiments provide a kind of preparation method of prussian blue nano granule of zinc doping, comprise the following steps:
Step one: be dissolved in 50mL ethanol by 422mg potassium ferrocyanide, 800mg diethyl pentetic acid, mixing and stirring, is mixed with solution A;
Step 2: be dissolved in 25mL ethanol by 162mg iron chloride, 400mg diethyl pentetic acid, mixing and stirring, is mixed with B solution;
Step 3: be dissolved in by 236mg zinc methacrylate in 25mL ethanol, mixing and stirring, is mixed with C solution;
Step 4: C solution magnetic agitation is even, is heated to 60 DEG C and the 1h that refluxes, then adds B solution, mixing and stirring, and then dropwise add solution A, magnetic agitation reaction 3h, and centrifugalize obtains intermediate product D;
Step 5: intermediate product D is dissolved in 100mL ethanol, be heated to 60 DEG C, then 50mg azo-bis-iso-dimethyl is added, magnetic agitation reaction 5min, add 10 milliliters of O-(2-carboxyethyl) PEG methyl ether methacrylate again, magnetic agitation reaction 1h, cool to room temperature, adopts deionized water dialysis to purify and obtains the prussian blue nano granule of zinc doping.
Embodiment 3
Present embodiments provide a kind of preparation method of prussian blue nano granule of zinc doping, comprise the following steps:
Step one: be dissolved in 50mL ethanol by 484mg sodium ferrocyanide, 500mg malic acid, mixing and stirring, is mixed with solution A;
Step 2: be dissolved in 25mL ethanol by 127mg ferrous chloride, 500mg malic acid, mixing and stirring, is mixed with B solution;
Step 3: be dissolved in by 236mg zinc methacrylate in 25mL ethanol, mixing and stirring, is mixed with C solution;
Step 4: C solution magnetic agitation is even, is heated to 100 DEG C and the 1h that refluxes, then adds B solution, mixing and stirring, and then dropwise add solution A, magnetic agitation reaction 2h, and centrifugalize obtains intermediate product D;
Step 5: intermediate product D is dissolved in 100mL ethanol, be heated to 100 DEG C, then 20mg 2,2'-Azobis(2,4-dimethylvaleronitrile) is added, magnetic agitation reaction 10min, add 4 milliliters of O-(2-amino-ethyl) PEG methyl ether methacrylate again, magnetic agitation reaction 1h, cool to room temperature, adopts deionized water dialysis to purify and obtains the prussian blue nano granule of zinc doping.
Embodiment 4
Present embodiments provide a kind of preparation method of prussian blue nano granule of zinc doping, comprise the following steps:
Step one: be dissolved in 50mL ethylene glycol by 284mg ferrous ammonium cyanide, 300mg tartaric acid, mixing and stirring, is mixed with solution A;
Step 2: be dissolved in 25mL ethylene glycol by 81mg iron chloride, 300mg tartaric acid, mixing and stirring, is mixed with B solution;
Step 3: be dissolved in by 470mg zinc methacrylate in 25mL ethylene glycol, mixing and stirring, is mixed with C solution;
Step 4: C solution magnetic agitation is even, is heated to 90 DEG C and the 1h that refluxes, then adds B solution, mixing and stirring, and then dropwise add solution A, magnetic agitation reaction 2h, and centrifugalize obtains intermediate product D;
Step 5: intermediate product D is dissolved in 100mL ethanol, be heated to 70 DEG C, then 100mg azodiisobutyronitrile is added, magnetic agitation reaction 2min, add 15 milliliters of PEG methacrylates again, magnetic agitation reaction 1h, cool to room temperature, adopts deionized water dialysis to purify and obtains the prussian blue nano granule of zinc doping.
Embodiment 5
Present embodiments provide a kind of preparation method of prussian blue nano granule of zinc doping, comprise the following steps:
Step one: be dissolved in 50mL ethylene glycol by 900mg sodium ferricyanide, 460mg succinic acid, mixing and stirring, is mixed with solution A;
Step 2: be dissolved in 25mL ethylene glycol by 127mg ferrous chloride, 230mg succinic acid, mixing and stirring, is mixed with B solution;
Step 3: be dissolved in by 470mg zinc methacrylate in 25mL ethylene glycol, mixing and stirring, is mixed with C solution;
Step 4: C solution magnetic agitation is even, is heated to 80 DEG C and the 1h that refluxes, then adds B solution, mixing and stirring, and then dropwise add solution A, magnetic agitation reaction 2h, and centrifugalize obtains intermediate product D;
Step 5: intermediate product D is dissolved in 100mL ethanol, be heated to 70 DEG C, then 100mg azodiisobutyronitrile is added, magnetic agitation reaction 4min, add 7 milliliters of O-(2-carboxyethyl) PEG methacrylate again, magnetic agitation reaction 2h, cool to room temperature, adopts deionized water dialysis to purify and obtains the prussian blue nano granule of zinc doping.
Embodiment 6
Present embodiments provide a kind of preparation method of prussian blue nano granule of zinc doping, comprise the following steps:
Step one: be dissolved in 50mL ethylene glycol by 235mg ferrous ammonium cyanide, 300mg tartaric acid, mixing and stirring, is mixed with solution A;
Step 2: be dissolved in 25mL ethylene glycol by 162mg iron chloride, 300mg tartaric acid, mixing and stirring, is mixed with B solution;
Step 3: be dissolved in by 236mg zinc methacrylate in 25mL ethylene glycol, mixing and stirring, is mixed with C solution;
Step 4: C solution magnetic agitation is even, is heated to 80 DEG C and the 1h that refluxes, then adds B solution, mixing and stirring, and then dropwise add solution A, magnetic agitation reaction 2h, and centrifugalize obtains intermediate product D;
Step 5: intermediate product D is dissolved in 100mL ethanol, be heated to 70 DEG C, then 60mg azodiisobutyronitrile is added, magnetic agitation reaction 8min, add 6 milliliters of O-(2-amino-ethyl) PEG methacrylate again, magnetic agitation reaction 3h, cool to room temperature, adopts deionized water dialysis to purify and obtains the prussian blue nano granule of zinc doping.
Embodiment 7
Present embodiments provide a kind of preparation method of prussian blue nano granule of zinc doping, comprise the following steps:
Step one: be dissolved in 50mL ethylene glycol by 466mg sodium ferrocyanide, 300mg tartaric acid, mixing and stirring, is mixed with solution A;
Step 2: be dissolved in 25mL ethylene glycol by 320mg iron chloride, 300mg tartaric acid, mixing and stirring, is mixed with B solution;
Step 3: be dissolved in by 118mg zinc methacrylate in 25mL ethylene glycol, mixing and stirring, is mixed with C solution;
Step 4: C solution magnetic agitation is even, is heated to 80 DEG C and the 1h that refluxes, then adds B solution, mixing and stirring, and then dropwise add solution A, magnetic agitation reaction 2h, and centrifugalize obtains intermediate product D;
Step 5: intermediate product D is dissolved in 100mL ethanol, be heated to 70 DEG C, then 50mg azodiisobutyronitrile is added, magnetic agitation reaction 2min, add 10 milliliters of PEG methyl ether methacrylate again, magnetic agitation reaction 4h, cool to room temperature, adopts deionized water dialysis to purify and obtains the prussian blue nano granule of zinc doping.
Embodiment 8
Present embodiments provide a kind of preparation method of prussian blue nano granule of zinc doping, comprise the following steps:
Step one: be dissolved in 50mL ethylene glycol by 466mg sodium ferrocyanide, 800mg citric acid, mixing and stirring, is mixed with solution A;
Step 2: be dissolved in 25mL ethylene glycol by 162mg iron chloride, 400mg citric acid, mixing and stirring, is mixed with B solution;
Step 3: be dissolved in by 236mg zinc methacrylate in 25mL ethylene glycol, mixing and stirring, is mixed with C solution;
Step 4: C solution magnetic agitation is even, is heated to 80 DEG C and the 1h that refluxes, then adds B solution, mixing and stirring, and then dropwise add solution A, magnetic agitation reaction 4h, and centrifugalize obtains intermediate product D;
Step 5: intermediate product D is dissolved in 100mL ethanol, be heated to 70 DEG C, then 100mg azodiisobutyronitrile is added, magnetic agitation reaction 2min, add 12 milliliters of PEG methyl ether methacrylate again, magnetic agitation reaction 0.5h, cool to room temperature, adopts deionized water dialysis to purify and obtains the prussian blue nano granule of zinc doping.
The prussian blue nano granule uv absorption spectra experiment of embodiment 9 zinc doping
The prussian blue nano granule of zinc doping embodiment 1 prepared carries out uv absorption spectra experiment.The ultra-violet absorption spectrum of the prussian blue nano granule of zinc doping is measured in the interscan of ultraviolet spectra 500-900nm wave-length coverage.Experimental result as shown in Figure 1.
Experimental result shows: compared with business-like Prussian blue ultraviolet and visible absorption peak, the scope of business-like Prussian blue ultraviolet and visible absorption peak is 680-690nm, and the Prussian blue absworption peak red shift of the zinc doping of gained of the present invention is to about 710-730nm, red shift make it possible to absorb further from the absorption bands scope of biological tissue, wavelength is longer, penetration depth in biological tissue is darker, thus it is higher to obtain signal to noise ratio, deeper photoacoustic signal.
The prussian blue nano granule of embodiment 10 zinc doping and the Prussian blue photoacoustic signal contrast experiment of commercialization
The prussian blue nano granule of the zinc doping that embodiment 1 is prepared with commercially produce Prussian bluely carry out photoacoustic signal contrast experiment.
(1) the prussian blue nano granule photoacoustic signal experiment of zinc doping
A, the prussian blue nano granule of zinc doping embodiment 1 synthesized get 1mg, soluble in water, are mixed with A1, A2, A3, A4 solution that Concentraton gradient is respectively 0.5mg/mL, 0.25mg/mL, 0.125mg/mL, 0.0625mg/mL;
The preparation of b, 2% agarose solution: get 2g agarose and add heating for dissolving in 98g water, preparation obtains the agarose solution that concentration is 2%;
C, A1, A2, A3, A4 solution respectively with 200 μ L concentration of getting 200 μ L are the agarose solution mixing of 2%, in successively in imitative mould four holes of instillation, and cooling curing;
D, the imitative body prepared is placed in photoacoustic imaging system carries out signals collecting, adjusting wavelength is 720nm, and light energy is 0.8mJ, tests its photoacoustic signal, and result as shown in Figure 2.
(2) the Prussian blue optical signal experiment of commercialization
A, select the water miscible Prussian blue KFe [Fe (CN) commercially produced
6] carry out optical signal experiment, the KFe [Fe (CN) of water-soluble
6] 1mg, soluble in water, be mixed with B1, B2, B3, B4 solution that Concentraton gradient is respectively 0.5mg/mL, 0.25mg/mL, 0.125mg/mL, 0.0625mg/mL;
The preparation of b, 2% agarose solution: get 2g agarose and add heating for dissolving in 98g water, preparation obtains the agarose solution that concentration is 2%;
C, B1, B2, B3, B4 solution respectively with 200 μ L concentration of getting 200 μ L are the agarose solution mixing of 2%, in successively in imitative mould four holes of instillation, and cooling curing;
D, the imitative body prepared is placed in photoacoustic imaging system carries out signals collecting, adjusting wavelength is 720nm, and light energy is 0.8mJ, tests its photoacoustic signal, and result as shown in Figure 3.
Experimental result shows: with business-like Prussian blue KFe [Fe (CN)
6] compare, the photoacoustic signal of the prussian blue nano granule of zinc doping of the present invention strengthens clearly, and efficiency of light absorption is higher, and stability is better.
In sum, the crosslinked upper organic layer of prussian blue nano aggregation of particles of zinc doping provided by the invention, to stratum nucleare nano-particle, there is good protective effect, and the amino of organic layer, carboxyl or hydroxyl make nano-particle have good water solublity, improve the biocompatibility of nano-particle, for further finishing and antibody grafting provide condition; The thickness of organic layer can by controlling the material concentration of polyreaction, and reaction temperature and response time regulate, and react without other by-products, environmental protection, operation is simple; In nano-particle, the prussian blue nano granule of kernel zinc doping is as light absorption material, and efficiency of light absorption is higher, and stability is better; Zinc and ferrum are all micro elements needed by human, and two kinds of elements are absorbed with the pay-as-you-go operation mutually restricted in vivo, without other heavy metal ion, have increased substantially biocompatibility.
Claims (10)
1. a preparation method for the prussian blue nano granule of zinc doping, is characterized in that, comprise the following steps:
Step one: be dissolved in solvent by six cyanogen network ferrum acids, organic acid, after mixing and stirring, be mixed with solution A, wherein contains six cyanogen network ferrum acid 0.002-0.02g, organic acid 0.002-0.02g in every milliliter of solution A;
Step 2: be dissolved in solvent by iron chloride salt, organic acid, after mixing and stirring, be mixed with B solution, wherein contains iron chloride salt 0.002-0.02g, organic acid 0.002-0.02g in every milliliter of B solution;
Step 3: be dissolved in by zinc salt in solvent, after mixing and stirring, is mixed with C solution, wherein contains zinc salt 0.002-0.02g in every milliliter of C solution;
Step 4: C solution magnetic agitation is even, is heated to 20-100 DEG C and the 0.5-3h that refluxes, then adds B solution, mixing and stirring, and then dropwise add solution A, magnetic agitation reaction 0.5-4h, and centrifugalize obtains intermediate product D; Wherein, the mass ratio of solution A and B solution is 1:0.2-1:2, and the mass ratio of B solution and C solution is 1:10-10:1;
Step 5: intermediate product D is dissolved in solvent, is heated to 50-120 DEG C, then add initiator, magnetic agitation reaction 2-10min, then add polymer, magnetic agitation reaction 0.5-4h, cool to room temperature, adopts deionized water dialysis to purify and obtains the prussian blue nano granule of this zinc doping; Wherein, the mass ratio of intermediate product D, polymer, initiator is (0.05-0.5): (3-15): (0.02-0.1).
2. preparation method according to claim 1, is characterized in that, described six cyanogen network ferrum acids comprise one or more the combination in potassium ferrocyanide, the potassium ferricyanide, sodium ferrocyanide, sodium ferricyanide, ferrous ammonium cyanide and ammonium-cu hexacyanoferrate.
3. preparation method according to claim 1, is characterized in that, described organic acid comprises one or more the combination in citric acid, tartaric acid, malic acid, succinic acid and diethyl pentetic acid.
4. preparation method according to claim 1, is characterized in that, described solvent comprises ethanol and/or ethylene glycol.
5. preparation method according to claim 1, is characterized in that, described iron chloride salt comprises iron chloride and/or ferrous chloride.
6. preparation method according to claim 1, is characterized in that, described zinc salt is zinc methacrylate.
7. preparation method according to claim 1, is characterized in that, the initiator in described step 5 comprises one or more the combination in azodiisobutyronitrile, azo-bis-iso-dimethyl and 2,2'-Azobis(2,4-dimethylvaleronitrile).
8. preparation method according to claim 1, it is characterized in that, the polymer in described step 5 comprises one or more the combination in PEG methyl ether methacrylate, PEG methacrylate, O-(2-carboxyethyl) PEG methacrylate, O-(2-carboxyethyl) PEG methyl ether methacrylate, O-(2-amino-ethyl) PEG methacrylate and O-(2-amino-ethyl) PEG methyl ether methacrylate.
9. a prussian blue nano granule for zinc doping prepared by the preparation method described in any one of claim 1-8, is characterized in that, the ultraviolet and visible absorption peak of the prussian blue nano granule of this zinc doping is between 710 nanometers to 730 nanometers.
10. the prussian blue nano granule of zinc doping according to claim 9 is as magnetic resonance and the application clinically of the difunctional image-forming contrast medium of optoacoustic.
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| CN107082438A (en) * | 2017-04-28 | 2017-08-22 | 武汉理工大学 | Prussian blue nano floral structure material and its preparation and application |
| CN107486130A (en) * | 2017-09-29 | 2017-12-19 | 天津碧水源膜材料有限公司 | Prussian-blue takes off the application in ammonium material preparation method and the de- ammonium of sewage |
| CN107486131A (en) * | 2017-09-29 | 2017-12-19 | 天津碧水源膜材料有限公司 | Zinc ferrocyanide sodium takes off the preparation method of ammonium material and the application in sewage takes off ammonium |
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| CN107082438A (en) * | 2017-04-28 | 2017-08-22 | 武汉理工大学 | Prussian blue nano floral structure material and its preparation and application |
| CN107082438B (en) * | 2017-04-28 | 2019-05-24 | 武汉理工大学 | Prussian blue nano floral structure material and its preparation and application |
| CN107486130A (en) * | 2017-09-29 | 2017-12-19 | 天津碧水源膜材料有限公司 | Prussian-blue takes off the application in ammonium material preparation method and the de- ammonium of sewage |
| CN107486131A (en) * | 2017-09-29 | 2017-12-19 | 天津碧水源膜材料有限公司 | Zinc ferrocyanide sodium takes off the preparation method of ammonium material and the application in sewage takes off ammonium |
| CN107486131B (en) * | 2017-09-29 | 2020-05-05 | 天津碧水源膜材料有限公司 | Preparation method of zinc ferricyanide sodium deamination material and application of zinc ferricyanide sodium deamination material in sewage deamination |
| CN107486130B (en) * | 2017-09-29 | 2020-07-21 | 天津碧水源膜材料有限公司 | Preparation method of prussian blue compound deammoniation material and application of prussian blue compound deammoniation material in sewage deammoniation |
| CN109276714A (en) * | 2018-10-25 | 2019-01-29 | 绍兴文理学院 | A kind of Zn2+Adulterate the preparation method of ultra-small grain size prussian blue nano probe |
| CN110137491A (en) * | 2019-06-05 | 2019-08-16 | 上海纳米技术及应用国家工程研究中心有限公司 | A kind of preparation method of anode material for lithium-ion batteries and products thereof and application |
| CN112402449A (en) * | 2020-11-16 | 2021-02-26 | 安徽农业大学 | Prussian-like blue nano material and preparation method and application thereof |
| CN112402449B (en) * | 2020-11-16 | 2022-05-06 | 安徽农业大学 | Prussian-like blue nano material and preparation method and application thereof |
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