CN105288668B - A kind of prussian blue nano particle of zinc doping and its preparation method and application - Google Patents
A kind of prussian blue nano particle of zinc doping and its preparation method and application Download PDFInfo
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Abstract
The invention provides a kind of preparation method of the prussian blue nano particle of zinc doping, the preparation method is using six cyanogen network iron acids and zinc methacrylate as raw material, it is equipped with the organic acid of certain concentration, the prussian blue nano particle of zinc doping of the surface with double bond has been prepared, has then carried the organic layer of the functional groups such as carboxyl, amino, hydroxyl in nano grain surface modification by polymerisation again.Another object of the present invention also resides in the prussian blue nano particle for providing the zinc doping that above-mentioned preparation method is prepared and the nano particle as application of the contrast agent in the difunctional imaging of magnetic resonance and optoacoustic clinically.The prussian blue nano particle of zinc doping prepared by the present invention has water-soluble, biocompatibility and photo and thermal stability well, and nano grain surface has amino, carboxyl or hydroxyl etc., very favorable condition is provided for further surface modification and antibody grafting.
Description
Technical field
The invention belongs to biomedical materials field, and in particular to the prussian blue nano particle and its system of a kind of zinc doping
Preparation Method, as well as the application of magnetic resonance and the difunctional image-forming contrast medium of optoacoustic clinically.
Background technology
Bio-imaging technology mainly includes optical imagery, magnetic resonance imaging, ultrasonic imaging and positron imaging etc..Optics into
As having high sensitivity, detection time is short, but has the characteristics that limitation to deep tissues imaging, and magnetic resonance imaging can carry out depth
Layer tissue is imaged, but sensitivity is relatively low, thus, two kinds of imaging techniques have good mutual supplement with each other's advantages feature.Photoacoustic imaging is near
A kind of emerging non-invasive imaging technique to grow up over year, its principle is to cause thermal expansion using after material absorbing luminous energy
And caused sound wave this principle is imaged.Relative to other optical image technologies, photoacoustic imaging has that resolution ratio is higher,
The advantages such as penetration depth is larger.Because biological tissue does not absorb significantly near infrared light region, it is penetrated to tissue
It is deeper, so introducing near infrared region there is the photoacoustic imaging contrast agent absorbed by force to improve the signal to noise ratio of photoacoustic imaging, profit
It can be realized as the excitation source of photoacoustic imaging by the use of near-infrared laser and the tissue of deeper is imaged.
Biomedical contrast agents material has obtained extensive pass with the needs of development and research and the diagnosis of imaging technique
Note.Current magnetic resonance contrast agent mainly includes gadolinium class contrast agent and ferroso-ferric oxide class contrast agent, gadolinium class contrast agent relaxation rate
It is relatively low, the risk that kidney source sexual system fibrosis occurs is had during using contrast agent containing gadolinium, there are a hundreds of deaths, and four oxidations
Metabolic problems are not yet resolved inside three-iron, it is therefore necessary to the magnetic resonance contrast agent of Development of Novel.Photoacoustic contrast agent master
To include the inorganic nano materials such as gold nano-material, copper sulfide nano material, graphene nano material and small molecule has engine dyeing
Material etc..Because gold nano-material heat endurance is poor, the biosafety issues of inorganic nano material are not resolved, small molecule
The shortcomings of organic dyestuff is easily affected by environment, and photostability is poor, and circulation time in vivo is short, therefore the photoacoustic contrast agent of Development of Novel
It is imperative.
Prussian blue is a kind of antidote for treating some heavy metal poisonings that clinical practice can be used as by FDA approvals, its
Structure is electron rich cyano group bridging ferric ion and ferrous ion forming face centered cubic lattice, and its shortcoming is insoluble
Yu Shui, thus can not be injected intravenously in vivo.Study and confirmed the Prussian blue imaging applications as MRI contrast agent
(J.Mater.Chem.,2010,20,5251-5259；Inorganic Chemistry Communications,2010,13,
58-61；) and photoacoustic contrast agent imaging applications (Chem.Commun., 2013,49,11029-11031；Biomaterials,
2014,35,9844-9852.).However, water miscible Prussian blue KFe [Fe (CN)6] due to potassium ion, intravenous injection
Using with limitation, and Fe4[Fe(CN)6]3It is again not soluble in water.
Therefore develop a kind of novel type radiographic contrast, based on Prussian blue nano particle can combine MRI imaging and optoacoustic into
Picture, the advantage of two kinds of imaging techniques is given full play to, while overcome the inferior position of prussian blue nano particle again, examined for research and clinic
The relatively reliable information of disconnected offer is one of this area urgent problem to be solved.
The content of the invention
In order to solve above-mentioned technical problem, Prussian blue it is an object of the invention to provide a kind of zinc doping is received
The preparation method of rice grain, this method introduce double bond by adulterating zinc methacrylate in prussian blue nano particle surface, and
Organic layer is superscribed by prussian blue nano particle surface of the polymerisation in zinc doping.
A kind of prussian blue nano particle of the zinc doping prepared the present invention also aims to provide above-mentioned preparation method.
The present invention also aims to provide a kind of prussian blue nano particle of above-mentioned zinc doping as magnetic resonance and light
The application of the difunctional image-forming contrast medium of sound clinically.
The purpose of the present invention is achieved by the following technical programs：
A kind of preparation method of the prussian blue nano particle of zinc doping, comprises the following steps：
Step 1：Six cyanogen network iron acids, organic acid are dissolved in solvent, after being mixed evenly, it is molten to be configured to A
Liquid, wherein containing six cyanogen network iron acid 0.002-0.02g, organic acid 0.002-0.02g in every milliliter of solution A；
Step 2：Iron chloride salt, organic acid are dissolved in solvent, after being mixed evenly, are configured to B solution, wherein often
Contain iron chloride salt 0.002-0.02g, organic acid 0.002-0.02g in milliliter B solution；
Step 3：Zinc salt is dissolved in solvent, after being mixed evenly, is configured to C solution, wherein in every milliliter of C solution
Contain zinc salt 0.002-0.02g；
Step 4：C solution magnetic agitation is uniform, it is heated to 60-100 DEG C and the 0.5-3h that flows back, adds B solution, mixes
Conjunction stirs, and solution A is then added dropwise again, magnetic agitation reaction 0.5-4h, is centrifugally separating to obtain intermediate product D；Wherein,
The mass ratio of solution A and B solution is 1:0.2-1:2, 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 adds initiator, magnetic agitation is anti-
2-10min is answered, polymer is added, magnetic agitation reaction 0.5-4h, is cooled to room temperature, obtained using deionized water dialysis purification
The prussian blue nano particle of the zinc doping, wherein intermediate product D, polymer, the mass ratio of initiator are (0.05-0.5):
(3-15):(0.02-0.1), as long as the addition of solvent guarantees fully to dissolve intermediate product D.Using deionized water
Product obtained by dialysis can be dissolved in water, and therapeutic medical Prussian blue antidote is insoluble in water.
In above-mentioned preparation method, it is preferable that the six cyanogen network iron acid can include potassium ferrocyanide, iron cyaniding
One or more combinations in potassium, sodium ferrocyanide, the sodium ferricyanide, ferrous ammonium cyanide and ammonium-cu hexacyanoferrate etc..
In above-mentioned preparation method, it is preferable that the organic acid can include citric acid, tartaric acid, malic acid, butanedioic acid and
One or more combinations in diethyl pentetic acid etc..
In above-mentioned preparation method, it is preferable that the solvent can include ethanol and/or ethylene glycol.
In above-mentioned preparation method, it is preferable that the iron chloride salt can include iron chloride and/or frerrous chloride.
In above-mentioned preparation method, it is preferable that the zinc salt can be zinc methacrylate.Inner nuclear layer is general using zinc doping
Shandong scholar's indigo plant nano particle is as light absorbs material, and efficiency of light absorption is higher, and stability is preferable.Zinc and iron are all needed by human micro-
Secondary element, and two kinds of elements absorb in vivo the pay-as-you-go operation mutually restricted, and without other heavy metal ion, significantly
Improve biocompatibility.
In above-mentioned preparation method, it is preferable that it is different can to include azodiisobutyronitrile, azo two for initiator in the step 5
One or more combinations in butyric acid dimethyl ester and ABVN etc..
In above-mentioned preparation method, it is preferable that polymer can include PEG methyl ether methyl in the step 5
Acrylate, PEG methacrylate, O- (2- carboxyethyls) PEG methacrylate, O- (2- carboxylic second
Base) PEG methyl ether methacrylate, O- (2- amino-ethyls) PEG methacrylates and O- (2- amino
Ethyl) one or more combinations in PEG methyl ether methacrylate etc..It is crosslinked and is carried by polymerisation
The organic layer of the functional groups such as amino, carboxyl or hydroxyl, organic layer have good protective effect to stratum nucleare nano particle, surface
The nano particle that amino, carboxyl or hydroxyl make has water-soluble well, it is possible to increase the biocompatibility of nano particle, and
Amino, carboxyl or the hydroxyl on surface provide condition for further surface modification and antibody grafting.The thickness of organic layer simultaneously
It can be reacted without other accessory substances by controlling material concentration, reaction temperature and the reaction time of polymerisation to be adjusted, it is green
Colour circle is protected, and operation is simple.The present invention can be avoided in physiological conditions, in blood in Prussian blue outer layer covers organic layer
Other ions reacted with Prussian blue, influence the stabilization of Prussian blue body structure.
Present invention also offers a kind of prussian blue nano particle for the zinc doping being prepared using above-mentioned preparation method.
In the prussian blue nano particle of above-mentioned zinc doping, it is preferable that the prussian blue nano particle of the zinc doping
Ultraviolet and visible absorption peak is between 710 nanometers to 730 nanometers.
Present invention also offers the prussian blue nano particle of above-mentioned zinc doping as magnetic resonance and the difunctional imaging of optoacoustic
The application of contrast agent clinically.The nano particle inner nuclear layer can produce magnetic resonance letter for the prussian blue nano particle of zinc doping
Number and photoacoustic signal, outer layer copolymer organic layer is due to hydrophilic functional groups such as surface carboxyl groups, amino, hydroxyls, adding
The water solubility and biocompatibility of prussian blue nano particle.The ultraviolet and visible absorption peak of the nano particle falls to be arrived at 710 nanometers
Between 730 nanometers.The nano particle can be used as magnetic resonance and the difunctional image-forming contrast medium of optoacoustic, with reference to two kinds of imaging advantages, be
Medical diagnosis provides more comprehensively effective information.
Beneficial effect of the present invention：
(1) nano particle of the invention is crosslinked having with functional groups such as amino, carboxyl or hydroxyls by polymerisation
Machine layer.Organic layer has good protective effect to stratum nucleare nano particle, and amino, carboxyl or the hydroxyl on surface cause nano particle
With good water solubility, the biocompatibility of nano particle is improved, amino, carboxyl or the hydroxyl on surface are further table
Face is modified and antibody grafting provides condition；
(2) using the upper organic layer of polymerisation crosslinking in nanometer grain preparation method of the invention, the thickness of organic layer can
With the material concentration by controlling polymerisation, reaction temperature and reaction time are adjusted, and react without other accessory substances, green
Environmental protection, operation is simple；
(3) in the nano particle for preparing of the present invention prussian blue nano particle of kernel zinc doping as light absorbs material,
Efficiency of light absorption is higher, and stability is preferable；
(4) inner nuclear layer is the prussian blue nano particle of zinc doping in nano particle prepared by the present invention, and zinc and iron are all
Micro elements needed by human, and two kinds of elements absorb in vivo the pay-as-you-go operation mutually restricted, without other heavy metals from
Son, biocompatibility is greatly improved；
(5) controlled in nanometer grain preparation method of the invention using the particle size of organic acid control nano particle
Journey is more prone to regulate and control.
Brief description of the drawings
Fig. 1 is the UV-vis absorption spectrum figure of the prussian blue nano particle of zinc doping；
Fig. 2 is the photoacoustic signal figure of the prussian blue nano particle of zinc doping；
Fig. 3 is the Prussian blue KFe [Fe (CN) of commercialization6] photoacoustic signal figure.
Embodiment
In order to which technical characteristic, purpose and the beneficial effect of the present invention is more clearly understood, now to the skill of the present invention
Art scheme carry out it is described further below, but it is not intended that to the present invention can practical range restriction.
Embodiment 1
A kind of preparation method of the prussian blue nano particle of zinc doping is present embodiments provided, is comprised the following steps：
Step 1：The 329mg potassium ferricyanides, 400mg citric acids are dissolved in 50mL ethanol, is mixed evenly, is configured to A
Solution；
Step 2：127mg frerrous chlorides, 400mg citric acids are dissolved in 25mL ethanol, is mixed evenly, is configured to B
Solution；
Step 3：236mg zinc methacrylates are dissolved in 25mL ethanol, are mixed evenly, are configured to C solution；
Step 4：C solution magnetic agitation is uniform, 80 DEG C and the 1h that flows back are heated to, adds B solution, is mixed equal
It is even, solution A is then added dropwise again, magnetic agitation reaction 3h, is centrifugally separating to obtain intermediate product D；
Step 5：Intermediate product D is dissolved in 100mL ethanol, is heated to 70 DEG C, then adds the isobutyl of 50mg azos two
Nitrile, magnetic agitation reaction 5min, adds 7.5 milliliters of PEG methyl ether methacrylates, and magnetic agitation reacts 1h,
Room temperature is cooled to, the prussian blue nano particle adulterated using deionized water dialysis purification.
Embodiment 2
A kind of preparation method of the prussian blue nano particle of zinc doping is present embodiments provided, is comprised the following steps：
Step 1：422mg potassium ferrocyanides, 800mg diethyl pentetic acids are dissolved in 50mL ethanol, mixed
Uniformly, it is configured to solution A；
Step 2：162mg iron chloride, 400mg diethyl pentetic acids are dissolved in 25mL ethanol, mixed equal
It is even, it is configured to B solution；
Step 3：236mg zinc methacrylates are dissolved in 25mL ethanol, are mixed evenly, are configured to C solution；
Step 4：C solution magnetic agitation is uniform, 60 DEG C and the 1h that flows back are heated to, adds B solution, is mixed equal
It is even, solution A is then added dropwise again, magnetic agitation reaction 3h, is centrifugally separating to obtain intermediate product D；
Step 5：Intermediate product D is dissolved in 100mL ethanol, is heated to 60 DEG C, then adds the isobutyric acid of 50mg azos two
Dimethyl ester, magnetic agitation reaction 5min, adds 10 milliliters of O- (2- carboxyethyls) PEG methyl ether methacrylate, magnetic
Power stirring reaction 1h, is cooled to room temperature, and the prussian blue nano particle of zinc doping is obtained using deionized water dialysis purification.
Embodiment 3
A kind of preparation method of the prussian blue nano particle of zinc doping is present embodiments provided, is comprised the following steps：
Step 1：484mg sodium ferrocyanides, 500mg malic acid are dissolved in 50mL ethanol, are mixed evenly, is prepared
Into solution A；
Step 2：127mg frerrous chlorides, 500mg malic acid are dissolved in 25mL ethanol, is mixed evenly, is configured to B
Solution；
Step 3：236mg zinc methacrylates are dissolved in 25mL ethanol, are mixed evenly, are configured to C solution；
Step 4：C solution magnetic agitation is uniform, 100 DEG C and the 1h that flows back are heated to, adds B solution, is mixed equal
It is even, solution A is then added dropwise again, magnetic agitation reaction 2h, is centrifugally separating to obtain intermediate product D；
Step 5：Intermediate product D is dissolved in 100mL ethanol, is heated to 100 DEG C, then two different heptan of addition 20mg azos
Nitrile, magnetic agitation reaction 10min, adds 4 milliliters of O- (2- amino-ethyls) PEG methyl ether methacrylate, magnetic force
Stirring reaction 1h, is cooled to room temperature, and the prussian blue nano particle of zinc doping is obtained using deionized water dialysis purification.
Embodiment 4
A kind of preparation method of the prussian blue nano particle of zinc doping is present embodiments provided, is comprised the following steps：
Step 1：284mg ferrous ammonium cyanides, 300mg tartaric acid are dissolved in 50mL ethylene glycol, is mixed evenly, matches somebody with somebody
Solution A is made；
Step 2：81mg iron chloride, 300mg tartaric acid are dissolved in 25mL ethylene glycol, is mixed evenly, is configured to B
Solution；
Step 3：470mg zinc methacrylates are dissolved in 25mL ethylene glycol, are mixed evenly, are configured to C solution；
Step 4：C solution magnetic agitation is uniform, 90 DEG C and the 1h that flows back are heated to, adds B solution, is mixed equal
It is even, solution A is then added dropwise again, magnetic agitation reaction 2h, is centrifugally separating to obtain intermediate product D；
Step 5：Intermediate product D is dissolved in 100mL ethanol, is heated to 70 DEG C, then adds the isobutyl of 100mg azos two
Nitrile, magnetic agitation reaction 2min, 15 milliliters of PEG methacrylates are added, magnetic agitation reaction 1h, are cooled to
Room temperature, the prussian blue nano particle of zinc doping is obtained using deionized water dialysis purification.
Embodiment 5
A kind of preparation method of the prussian blue nano particle of zinc doping is present embodiments provided, is comprised the following steps：
Step 1：The 900mg sodium ferricyanides, 460mg butanedioic acids are dissolved in 50mL ethylene glycol, are mixed evenly, is prepared
Into solution A；
Step 2：127mg frerrous chlorides, 230mg butanedioic acids are dissolved in 25mL ethylene glycol, are mixed evenly, is prepared
Into B solution；
Step 3：470mg zinc methacrylates are dissolved in 25mL ethylene glycol, are mixed evenly, are configured to C solution；
Step 4：C solution magnetic agitation is uniform, 80 DEG C and the 1h that flows back are heated to, adds B solution, is mixed equal
It is even, solution A is then added dropwise again, magnetic agitation reaction 2h, is centrifugally separating to obtain intermediate product D；
Step 5：Intermediate product D is dissolved in 100mL ethanol, is heated to 70 DEG C, then adds the isobutyl of 100mg azos two
Nitrile, magnetic agitation reaction 4min, adds 7 milliliters of O- (2- carboxyethyls) PEG methacrylate, magnetic agitation is anti-
2h is answered, is cooled to room temperature, the prussian blue nano particle of zinc doping is obtained using deionized water dialysis purification.
Embodiment 6
A kind of preparation method of the prussian blue nano particle of zinc doping is present embodiments provided, is comprised the following steps：
Step 1：235mg ferrous ammonium cyanides, 300mg tartaric acid are dissolved in 50mL ethylene glycol, is mixed evenly, matches somebody with somebody
Solution A is made；
Step 2：162mg iron chloride, 300mg tartaric acid are dissolved in 25mL ethylene glycol, is mixed evenly, is configured to B
Solution；
Step 3：236mg zinc methacrylates are dissolved in 25mL ethylene glycol, are mixed evenly, are configured to C solution；
Step 4：C solution magnetic agitation is uniform, 80 DEG C and the 1h that flows back are heated to, adds B solution, is mixed equal
It is even, solution A is then added dropwise again, magnetic agitation reaction 2h, is centrifugally separating to obtain intermediate product D；
Step 5：Intermediate product D is dissolved in 100mL ethanol, is heated to 70 DEG C, then adds the isobutyl of 60mg azos two
Nitrile, magnetic agitation reaction 8min, adds 6 milliliters of O- (2- amino-ethyls) PEG methacrylate, magnetic agitation
3h is reacted, is cooled to room temperature, the prussian blue nano particle of zinc doping is obtained using deionized water dialysis purification.
Embodiment 7
A kind of preparation method of the prussian blue nano particle of zinc doping is present embodiments provided, is comprised the following steps：
Step 1：466mg sodium ferrocyanides, 300mg tartaric acid are dissolved in 50mL ethylene glycol, is mixed evenly, matches somebody with somebody
Solution A is made；
Step 2：320mg iron chloride, 300mg tartaric acid are dissolved in 25mL ethylene glycol, is mixed evenly, is configured to B
Solution；
Step 3：118mg zinc methacrylates are dissolved in 25mL ethylene glycol, are mixed evenly, are configured to C solution；
Step 4：C solution magnetic agitation is uniform, 80 DEG C and the 1h that flows back are heated to, adds B solution, is mixed equal
It is even, solution A is then added dropwise again, magnetic agitation reaction 2h, is centrifugally separating to obtain intermediate product D；
Step 5：Intermediate product D is dissolved in 100mL ethanol, is heated to 70 DEG C, then adds the isobutyl of 50mg azos two
Nitrile, magnetic agitation reaction 2min, adds 10 milliliters of PEG methyl ether methacrylates, and magnetic agitation reacts 4h,
Room temperature is cooled to, the prussian blue nano particle of zinc doping is obtained using deionized water dialysis purification.
Embodiment 8
A kind of preparation method of the prussian blue nano particle of zinc doping is present embodiments provided, is comprised the following steps：
Step 1：466mg sodium ferrocyanides, 800mg citric acids are dissolved in 50mL ethylene glycol, is mixed evenly, matches somebody with somebody
Solution A is made；
Step 2：162mg iron chloride, 400mg citric acids are dissolved in 25mL ethylene glycol, is mixed evenly, is configured to B
Solution；
Step 3：236mg zinc methacrylates are dissolved in 25mL ethylene glycol, are mixed evenly, are configured to C solution；
Step 4：C solution magnetic agitation is uniform, 80 DEG C and the 1h that flows back are heated to, adds B solution, is mixed equal
It is even, solution A is then added dropwise again, magnetic agitation reaction 4h, is centrifugally separating to obtain intermediate product D；
Step 5：Intermediate product D is dissolved in 100mL ethanol, is heated to 70 DEG C, then adds the isobutyl of 100mg azos two
Nitrile, magnetic agitation reaction 2min, add 12 milliliters of PEG methyl ether methacrylates, magnetic agitation reaction
0.5h, room temperature is cooled to, the prussian blue nano particle of zinc doping is obtained using deionized water dialysis purification.
The prussian blue nano particle uv absorption spectra experiment of the zinc doping of embodiment 9
The prussian blue nano particle for the zinc doping that embodiment 1 is prepared carries out uv absorption spectra experiment.
The ultra-violet absorption spectrum of the prussian blue nano particle of sweep measuring zinc doping in ultraviolet spectra 500-900nm wave-length coverages.It is real
It is as shown in Figure 1 to test result.
Test result indicates that：It is commercialized Prussian blue compared with commercialized Prussian blue ultraviolet and visible absorption peak
The scope of ultraviolet and visible absorption peak be 680-690nm, and the Prussian blue absworption peak red shift of the zinc doping of present invention gained is arrived
710-730nm or so, red shift allow to absorb further from biological tissue absorption bands scope, wavelength is longer, in biology
Penetration depth in tissue is deeper, higher so as to can obtain signal to noise ratio, deeper photoacoustic signal.
The prussian blue nano particle of the zinc doping of embodiment 10 is with being commercialized Prussian blue photoacoustic signal contrast experiment
The prussian blue nano particle for the zinc doping that embodiment 1 is prepared and the Prussian blue progress commercially produced
Photoacoustic signal contrast experiment.
(1) the prussian blue nano particle photoacoustic signal experiment of zinc doping
A, the prussian blue nano particle for the zinc doping for synthesizing embodiment 1 takes 1mg, soluble in water, is configured to concentration ladder
Degree is respectively 0.5mg/mL, 0.25mg/mL, 0.125mg/mL, 0.0625mg/mL A1, A2, A3, A4 solution；
B, the preparation of 2% agarose solution：Take 2g agaroses to add in 98g water to dissolve by heating, preparation obtains concentration as 2%
Agarose solution；
C, 200 μ L A1, A2, A3, A4 solution is taken to be dripped successively respectively with the agarose solution mixing that 200 μ L concentration are 2%
In entering in imitative four holes of mould, cooling and solidifying；
D, the imitative body prepared is placed in photoacoustic imaging system and carries out signal acquisition, adjusting wavelength 720nm, light energy
For 0.8mJ, its photoacoustic signal is tested, as a result as shown in Figure 2.
(2) it is commercialized Prussian blue optical signal experiment
A, from the water miscible Prussian blue KFe [Fe (CN) commercially produced6] enter traveling optical signal experiment, water-soluble
KFe [Fe (CN)6] 1mg, it is soluble in water, be configured to concentration gradient be respectively 0.5mg/mL, 0.25mg/mL, 0.125mg/mL,
0.0625mg/mL B1, B2, B3, B4 solution；
B, the preparation of 2% agarose solution：Take 2g agaroses to add in 98g water to dissolve by heating, preparation obtains concentration as 2%
Agarose solution；
C, 200 μ L B1, B2, B3, B4 solution is taken to be dripped successively respectively with the agarose solution mixing that 200 μ L concentration are 2%
In entering in imitative four holes of mould, cooling and solidifying；
D, the imitative body prepared is placed in photoacoustic imaging system and carries out signal acquisition, adjusting wavelength 720nm, light energy
For 0.8mJ, its photoacoustic signal is tested, as a result as shown in Figure 3.
Test result indicates that：With commercialized Prussian blue KFe [Fe (CN)6] compare, the Pu Lu of zinc doping of the invention
Clearly, efficiency of light absorption is higher, and stability is preferable for the photoacoustic signal enhancing of scholar's indigo plant nano particle.
In summary, the upper organic layer of prussian blue nano aggregation of particles crosslinking of zinc doping provided by the invention, to stratum nucleare
Nano particle has good protective effect, and the amino of organic layer, carboxyl or hydroxyl make nano particle with water-soluble well
Property, the biocompatibility of nano particle is improved, condition is provided for further surface modification and antibody grafting；The thickness of organic layer
Degree can be by controlling the material concentration of polymerisation, and reaction temperature and reaction time are adjusted, reacted without other accessory substances,
Green, operation is simple；The prussian blue nano particle of kernel zinc doping is as light absorbs material, light in nano particle
Absorption efficiency is higher, and stability is preferable；Zinc and iron are all micro elements needed by human, and two kinds of elements absorb have mutually in vivo
The pay-as-you-go operation of restriction, without other heavy metal ion, biocompatibility is greatly improved.
Claims (9)
1. the preparation method of the prussian blue nano particle of a kind of zinc doping, it is characterised in that comprise the following steps：
Step 1：Six cyanogen network iron acids, organic acid are dissolved in solvent, after being mixed evenly, are configured to solution A, its
In contain six cyanogen network iron acid 0.002-0.02g, organic acid 0.002-0.02g in every milliliter of solution A；
Step 2：Iron chloride salt, organic acid are dissolved in solvent, after being mixed evenly, are configured to B solution, wherein every milliliter of B
Contain iron chloride salt 0.002-0.02g, organic acid 0.002-0.02g in solution；
Step 3：Zinc salt is dissolved in solvent, after being mixed evenly, is configured to C solution, wherein containing in every milliliter of C solution
Zinc salt 0.002-0.02g；
Step 4：C solution magnetic agitation is uniform, it is heated to 20-100 DEG C and the 0.5-3h that flows back, adds B solution, mixing is stirred
Mix uniformly, solution A is then added dropwise again, magnetic agitation reaction 0.5-4h, is centrifugally separating to obtain intermediate product D；Wherein, A is molten
Liquid and the mass ratio of B solution are 1:0.2-1:2, 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 adds initiator, magnetic agitation reaction 2-
10min, adds polymer, magnetic agitation reaction 0.5-4h, is cooled to room temperature, and the zinc is obtained using deionized water dialysis purification
The prussian blue nano particle of doping；Wherein, intermediate product D, polymer, the mass ratio of initiator are (0.05-0.5):(3-
15):(0.02-0.1)；
Wherein, the zinc salt is zinc methacrylate.
2. preparation method according to claim 1, it is characterised in that the six cyanogen network iron acid includes ferrocyanide
One or more combinations in potassium, the potassium ferricyanide, sodium ferrocyanide, the sodium ferricyanide, ferrous ammonium cyanide and ammonium-cu hexacyanoferrate.
3. preparation method according to claim 1, it is characterised in that the organic acid includes citric acid, tartaric acid, apple
One or more combinations in acid, butanedioic acid and diethyl pentetic acid.
4. preparation method according to claim 1, it is characterised in that the solvent includes ethanol and/or ethylene glycol.
5. preparation method according to claim 1, it is characterised in that the iron chloride salt includes iron chloride and/or chlorination
It is ferrous.
6. preparation method according to claim 1, it is characterised in that it is different that the initiator in the step 5 includes azo two
One or more combinations in butyronitrile, azo-bis-iso-dimethyl and ABVN.
7. preparation method according to claim 1, it is characterised in that the polymer in the step 5 includes poly- (second two
Alcohol) methyl ether methacrylate, PEG methacrylate, O- (2- carboxyethyls) PEG methacrylic acid
Ester, O- (2- carboxyethyls) PEG methyl ether methacrylate, O- (2- amino-ethyls) PEG methacrylic acid
One or more combinations in ester and O- (2- amino-ethyls) PEG methyl ether methacrylate.
8. the prussian blue nano particle of zinc doping prepared by the preparation method described in a kind of any one of claim 1-7, it is special
Sign is that the ultraviolet and visible absorption peak of the prussian blue nano particle of the zinc doping is between 710 nanometers to 730 nanometers.
9. the prussian blue nano particle of the zinc doping described in claim 8 is preparing magnetic resonance and the difunctional imaging contrast of optoacoustic
Application in agent.
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| 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 |
| 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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| WO2014146091A1 (en) * | 2013-03-15 | 2014-09-18 | Children's National Medical Center | Prussian blue-inspired constructs for multimodal imaging and therapy |
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