CN104258421B - A kind of noble metal/paramagnetic metal composite nanoparticle and application thereof - Google Patents
A kind of noble metal/paramagnetic metal composite nanoparticle and application thereof Download PDFInfo
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- CN104258421B CN104258421B CN201410464382.3A CN201410464382A CN104258421B CN 104258421 B CN104258421 B CN 104258421B CN 201410464382 A CN201410464382 A CN 201410464382A CN 104258421 B CN104258421 B CN 104258421B
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Abstract
The invention discloses a kind of noble metal/paramagnetic metal composite nanoparticle and application thereof, this noble metal/paramagnetic metal composite nanoparticle has that chemical stability is good, contrasting effects and the feature of good biocompatibility, can be used as MRI and CT and strengthens contrast medium.
Description
Technical field
The present invention relates to a kind of nanosecond medical science technical field, a kind of organometallic polymer composite nanoparticle
Preparation and application.
Technical background
Gold prepared by the scholar of home and abroad/gadolinium composite nanoparticle specifically includes that D.P.Cormode etc. prepares in the liquid phase
With Jin Weihe, phospholipid and containing the high density lipoprotein nanoparticle that gadolinium part is shell, particle diameter is about 9.7nm, can as fluorescence,
CT and MRI multimode contrast agent；Carbamide and the GdCl such as K.W.Hu3·6H2O mol ratio is that 4:1 returns in 91 DEG C of aqueous solutions
Flowing 4 hours preparation mean diameters is the Gd of 441nm2O(CO3)2·H2O granule, then generation silicon it is polymerized with tetraethoxysilane
The Gd of cladding2O(CO3)2·H2O/Si, through silane coupler modification of surfaces generation-NH2With electronegative nanometer gold after functional group
Combine with electrostatic interaction, be re-introduced into formaldehyde reduction gold chloride system and promote that gold shell growth is finally prepared with gold as shell
Gd2O(CO3)2·H2O/Si compound particle；It is 5nm and 10nm that D.Gerion etc. use Citrate Buffer first to prepare particle diameter
Jenner's rice glue, add phosphatization hydrogen meter face activating agent and make colloid-stabilised, then carry out Silanization reaction and outside subsequent treatment makes it
Layer coated silica, then it is prepared as the particle diameter Gd-DOTA-SiO less than 18nm with Gd-DOTA generation covalent bond2-Au
Compound particle；Y.Chen etc. utilize the mesopore silicon oxide containing abundant specific surface area that Gd-Si-DTPA is grafted onto Au@mSiO2
The hole of Nano capsule is prepared as Gd-Si-DTPA-Au@mSiO2The meso-porous nano capsule of core/shell structure, can be applicable to raw
The bimodal imaging of thing includes dark ground light scattering cell and T1Weighting MR imaging；Multilamellar organic mass shell cladding such as C.Alric is received
Meter Jin prepares nanoparticle, and its MRI potentiation stems from the gadolinium ion having in casing, and the gold being wrapped by checks X
Ray has stronger absorption, and result shows that this particle is applicable to dual form imaging；S.M.Nasiruzzaman etc. by gadolinium from
The citrate ion on sub-part (GdL) replacement nanometer gold surface prepares the compound particle GdL@Au of particle diameter about 12nm,
One of them compound particle comprises 1.4 × 103Individual GdL, can be used as MRI and CT contrast agent；The sulfydryl modification such as Moriggi
Smaller ligand DTTA (Dt) as protective agent, prepare the gold nanoclusters of Dt cladding, then with Gd3+Reaction obtains
Gold/gadolinium composite nanoparticle is used for MRI contrast agent.
Summary of the invention
First purpose of the present invention is to provide that a kind of chemical stability is good, contrasting effects and the noble metal of good biocompatibility
/ paramagnetic metal composite nanoparticle.
It is right as MRI and CT enhancing that second object of the present invention is to provide described noble metal/paramagnetic metal composite nanoparticle
Application than agent.
For achieving the above object, the present invention adopts the following technical scheme that
Noble metal involved in the present invention/paramagnetic metal composite nanoparticle by noble metal nano particles, organic bonding units and
Paramagnetic metal forms, and its preparation method comprises the following steps:
(1) polysuccinimide is dissolved in DMF (DMF), nitrogen protection and the lower intensification of stirring
To 30～65 DEG C, being subsequently adding compound A, stop heating after 24-48 hour, reactant mixture steams through dialysis, rotation, is dried
After obtain product I；Described compound A is 1-alkyl azide amine, and wherein the carbon atom number of alkyl is at 2～6；
(2) product I is dissolved in DMF, nitrogen protection and the lower dropping compound B of stirring and catalyst
DIPEA, in 30～80 DEG C reaction 24-48 hour after stop heating, reactant mixture through dialysis, rotation steam,
It is dried to obtain product II；Described compound B is p-aminophenyl thiophenol or L-cysteine hydrochloride or Mercaptamine；
(3) by product II and the N shown in formula (I)2-(4-alkynyl)-diethylenetriamines-four tert-butyl ester is dissolved in oxolane, then
The sodium ascorbate of addition brand-new and the aqueous solution of copper sulphate pentahydrate, extract and separate organic layer after reacting 2-4 hour at room temperature,
Steam through dialysis, rotation, be dried to obtain product III again；
(4) product III is dissolved in dichloromethane, under stirring, is slowly added dropwise trifluoroacetic acid, finish room temperature reaction 24-48 little
Stopping time after, rotation is evaporated off dichloromethane and trifluoroacetic acid, adds ether ultrasonic disperse, and separating, washing, drying obtains
Product IV；
(5) product IV being dissolved in ultra-pure water, the aqueous solution of dropping compound C, a complete regulation pH value is to 8-9, so
Rear stirring 1-2 hour, reactant mixture is through dialysing, being dried to obtain product V；Described compound C is selected from paramagnetic lanthanide series metal
Chloride；
(6) preparation gold or Nano silver grain；
(7) product V is dissolved in dimethyl sulfoxide (DMSO), and adds step (6) freshly prepd gold or Nano silver grain,
After reacting 12-24 hour under room temperature, reactant mixture steams through dialysis, rotation, is dried to obtain end product noble metal/paramagnetic metal
Composite nanoparticle.
Further, in step (1), polysuccinimide is 1:0.2～0.5 with the molar ratio of compound A.
Further, product I, compound B, the molar ratio of DIPEA are 1:0.8～0.5:0.8～0.5.
Further, in step (3), product II and N2-(4-alkynyl)-diethylenetriamines-four tert-butyl ester, sodium ascorbate,
The molar ratio of copper sulfate is 1:0.2～0.5:0.2～0.5:0.2～0.5.
Further, in step (4), product III is 1:4～8 with the molar ratio of trifluoroacetic acid.
Further, in step (5), product IV is 1:1～2 with the molar ratio of compound C.
Further, in step (6), the preparation method of gold or Nano silver grain is conventional reduction method, those skilled in the art
According to prior art can complete preparation, such as can be prepared as follows: by appropriate precious metal chemical complex (auric chloride,
Perchloric acid gold, silver nitrate etc.) it is dissolved in ultra-pure water, it is rapidly added proper amount of sodium citrate or sodium borohydride after being heated to boiling,
It is cooled to room temperature after reacting 5-10 minute, stops after continuing stirring 0.5-1 hour, obtain noble metal nano colloid solution.Wherein
Precious metal chemical complex is 1:4～8 with the mol ratio of sodium citrate or sodium borohydride.
Further, in step (7), product V rubs with feeding intake of the nano noble metal particles in nano-noble metal colloid solution
That ratio is 1:8～32.
Present invention also offers described noble metal/paramagnetic metal composite nanoparticle and strengthen answering of contrast medium as MRI and CT
With.
In the present invention, the molecular weight of macromolecular compound is all the mean molecule quantity using gel chromatography to record.
Compared with prior art, the present invention is successively reacted with polysuccinimide by compound A and compound B, is contained
There are multiple nitrine functional group and the copolymer of multiple mercapto functional group, and in this copolymer, introduce paramagnetic metal ion, obtain
Macromole paramagnetic metal coordination compound, and utilize Au-S key or Ag-S key by this coordination compound and Precious Metals-Gold or nano grain of silver subchain
Connect, thus prepare a kind of chemically stable noble metal/paramagnetic metal composite nanoparticle.This compound particle has the advantage that
(1) with macromolecular chain as bonding units, add the number of sites of gadolinium ion chelating, be favorably improved Relaxivity；(2)
There is multiple sulfydryl on macromolecular chain, stable chemical bond can be formed with noble metal nano particles, be favorably improved chemically stable
Property；(3) noble metal nano particles acts not only as the assembly platform of bonding units, simultaneously because its special permanent magnetism
Also can be as signal amplification unit, additionally the use of polysuccinimide makes this compound particle have good bio-compatible
Property, it is expected to agent as a comparison and is applied to medical imaging field.
Accompanying drawing explanation
Fig. 1 is the structural representation of gold/gadolinium composite nanoparticle that embodiment 1 prepares.
Fig. 2 is transmission electron microscope (TEM) image of gold/gadolinium composite nanoparticle that embodiment 1 prepares.
Fig. 3 is the MRI image of gold/gadolinium composite nanoparticle that embodiment 1 prepares, and is from left to right followed successively by that gold/gadolinium is compound to be received
Rice corpuscles, the tester (i.e. product V in embodiment 1) without gold, Magnevist Solution injection (Beijing North land Pharmaceutical stock
Part company limited), concentration is followed successively by 1.00,0.50,0.25,0.125,0.0625,0.0 × 10 from top to bottom-3mmol·L-1。
Fig. 4 is the CT image of gold/gadolinium composite nanoparticle that embodiment 1 prepares, 1-6 concentration is followed successively by 1.00,0.50,0.25,
0.125、0.0625、0.0×10-3mmol·L-1。
Detailed description of the invention
Following instance is provided in order to spy of the present invention is expanded on further.Obviously embodiments of the present invention are not limited to following enforcement
Example.
Embodiment 1
Step a, is dissolved in 5mL DMF (DMF) by polysuccinimide (molecular weight 20000) 1.0g
In solvent, and put in 100ml there-necked flask, stirring, logical nitrogen protection, add 0.4g1-nitrine third after being warming up to 60 DEG C
Amine, stops heating after reacting 24 hours.Reactant mixture is transferred to bag filter that molecular cut off is 3500 in DMF
Middle dialysis 48 hours, rotary evaporation is removed DMF and is obtained darkorange thick liquid, obtains product I after drying under reduced pressure.
Step b, is dissolved in 1.25g product I in 5mL DMF, logical nitrogen protection, stirs and adds 1.13g cysteamine salt
Hydrochlorate, 1.32g DIPEA, 60 DEG C reaction 24 hours after stop heating.It is transferred to mixture after reaction cut
Staying molecular weight is to dialyse 48 hours in ultra-pure water in 3500 bag filters, and rotary evaporation is removed major part water postlyophilization and obtained
Pale pink solid product II.
Step c, takes 1.25g product II and 3.90g N2-(4-alkynyl)-diethylenetriamines-four tert-butyl ester is dissolved in 5mL tetrahydrochysene furan
In muttering, add freshly prepared 1mol L-1Sodium ascorbate and each 1mL of copper sulphate pentahydrate aqueous solution, react at room temperature
Add 10mL water, 10mL dichloromethane after 2 hours, after stirring 2 minutes, be transferred to separatory funnel, retain organic layer, in
After dialysing 24 hours in dichloromethane, rotary evaporation removes dichloromethane, obtains product III after drying under reduced pressure.
Step d, is dissolved in 3.0g product III in 5mL dichloromethane, stirring, is slowly added dropwise 2mL trifluoroacetic acid under room temperature,
Room temperature reaction stopped after 24 hours, after rotation is evaporated off dichloromethane and trifluoroacetic acid, added 10mL ether ultrasonic disperse 10 points
Clock, obtains white solid powder, then washs three times with absolute ether, obtains product IV after drying under reduced pressure.
Step e, is dissolved in 2.5g product IV in 5mL ultra-pure water, by 0.7g GdCl3Soluble in water, and drip in three times,
Regulate pH value with saturated solution of sodium bicarbonate after dropping is 8-9 every time.After stirring 1 hour, reactant mixture is moved into thoroughly
Analysis bag, after dialysing 48 hours in water, lyophilization obtains product V.
Step f, is dissolved in 0.42g gold chloride in 20mL ultra-pure water, is heated to boiling, is rapidly added 1.00g sodium citrate,
It is cooled to room temperature after reacting 5 minutes, stops after continuing stirring 0.5 hour, obtain nano gold sol product VI.
Step g, is dissolved in 0.2g product V in 2mL DMSO, and drips 10mL concentration 0.001mol/L product VI,
Moving in 3500Da bag filter after reacting 12 hours under room temperature, dialyse 24 hours in ultra-pure water, rotation is evaporated off major part
After water under 3000 revs/min of revolutions centrifugation 30 minutes, take upper solution concentrate postlyophilization obtain end product.
End product is configured to variable concentrations aqueous solution (1.00,0.50,0.25,0.125,0.0625,0.0mmol L-1)。
It is subsequently placed in small test tube, in nuclear magnetic resonance imaging instrument and computed tomographic scanner, tests imaging effect.Knot
Fruit shows, in embodiment 1, composite nanoparticle possesses MRI reinforced effects (such as Fig. 3), and CT imaging effect (such as Fig. 4).
Its MRI relaxation rate is 47.6mM-1·s-1, the CT value of 1mM is 59.5/0.8.
Embodiment 2
Step a, is dissolved in 5mL DMF (DMF) by polysuccinimide (molecular weight 20000) 1.0g
In solvent, and put in 100ml there-necked flask, stirring, logical nitrogen protection, add 0.4g1-nitrine third after being warming up to 60 DEG C
Amine, stops heating after reacting 24 hours.Reactant mixture is transferred to bag filter that molecular cut off is 3500 in DMF
Middle dialysis 48 hours, rotary evaporation is removed DMF and is obtained darkorange thick liquid, obtains product I after drying under reduced pressure.
Step b, is dissolved in 1.25g product I in 5mL DMF, and logical nitrogen protection, stirring adds 1.13g cysteamine hydrochloric acid
Salt, 1.32g DIPEA, 60 DEG C reaction 24 hours after stop heating.It is transferred to retain by mixture after reaction
Molecular weight is to dialyse 48 hours in ultra-pure water in 3500 bag filters, and rotary evaporation is removed major part water postlyophilization and obtained light
Pink solid product II.
Step c, takes 1.25g product II and 3.90g N2-(4-alkynyl)-diethylenetriamines-four tert-butyl ester is dissolved in 5mL tetrahydrochysene furan
In muttering, add freshly prepared 1mol L-1Sodium ascorbate and each 1mL of copper sulphate pentahydrate aqueous solution, react at room temperature
Add 10mL water, 10mL dichloromethane after 2 hours, after stirring 2 minutes, be transferred to separatory funnel, retain organic layer, in
After dialysing 24 hours in dichloromethane, rotary evaporation removes dichloromethane, obtains product III after drying under reduced pressure.
Step d, is dissolved in 3.0g product III in 5mL dichloromethane, stirring, is slowly added dropwise 2mL trifluoroacetic acid under room temperature,
Room temperature reaction stopped after 24 hours, after rotation is evaporated off dichloromethane and trifluoroacetic acid, added 10mL ether ultrasonic disperse 10 points
Clock, obtains white solid powder, then washs three times with absolute ether, obtains product IV after drying under reduced pressure.
Step e, is dissolved in 2.5g product IV in 5mL ultra-pure water, by 0.7g GdCl3Soluble in water, and drip in three times,
Regulate pH value with saturated solution of sodium bicarbonate after dropping is 8-9 every time.After stirring 1 hour, reactant mixture is moved into thoroughly
Analysis bag, after dialysing 48 hours in water, lyophilization obtains product V.
Step f, is 2 × 10 by 25mL concentration with vigorous stirring in cryosel is bathed-3mol·L-1 Silver nitrate solutionIt is added drop-wise to
25mL concentration is 8 × 10-3mol·L-1In sodium borohydride aqueous solution, obtain the Nano silver grain hydrosol after reacting 30 minutes and produce
Thing VI.
Step g, is dissolved in 0.2g product V in 2mL DMSO, and drips 10mL concentration 0.001mol/L product VI,
Moving in 3500Da bag filter after reacting 12 hours under room temperature, dialyse 24 hours in ultra-pure water, rotation is evaporated off major part
After water under 3000 revs/min of revolutions centrifugation 30 minutes, take upper solution concentrate postlyophilization obtain end product.
Embodiment 3
Step a, is dissolved in polysuccinimide 1.0g in 5mLDMF solvent, and puts in 100ml there-necked flask, stirs
Mix, logical nitrogen protection, add 0.4g1-nitrine propylamine after being warming up to 60 DEG C, after reacting 24 hours, stop heating.Will reaction
Mixture is transferred to the bag filter that molecular cut off is 3500 and dialyses in DMF 48 hours, and rotary evaporation is removed DMF and obtained
Darkorange thick liquid, obtains product I after drying under reduced pressure.
Step b, is dissolved in 1.25g product I in 5mL DMF solvent, and logical nitrogen protection, stirring adds2.5g is to amino Phenylmercaptan., 1.32g DIPEA, reactant mixture was transferred to molecular cut off and is after 24 hours by 60 DEG C of reactions
Dialysing 48 hours in ultra-pure water in 3500 bag filters, rotary evaporation is removed major part water postlyophilization and is obtained product II.
Step c, takes 1.0g product II and 3.90g N2-(4-alkynyl)-diethylenetriamines-four tert-butyl ester is dissolved in 5mL tetrahydrochysene furan
In muttering, add freshly prepared 1mol L-1Sodium ascorbate and each 1mL of copper sulphate pentahydrate aqueous solution, react at room temperature
Add 10mL water, 10mL dichloromethane after 2 hours, after stirring 2 minutes, be transferred to separatory funnel, retain organic layer, in
After dialysing 24 hours in dichloromethane, rotary evaporation removes dichloromethane, obtains product III after drying under reduced pressure.
Step d, is dissolved in 3.0g product III in 5mL dichloromethane, stirring, is slowly added dropwise 2mL trifluoroacetic acid under room temperature,
Room temperature reaction stopped after 24 hours, after rotation is evaporated off dichloromethane and trifluoroacetic acid, added 10mL ether ultrasonic disperse 10 points
Clock, obtains white solid powder, then washs three times with absolute ether, obtains product IV after drying under reduced pressure.
Step e, is dissolved in 2.5g product IV in 5mL ultra-pure water, by 0.7g GdCl3Soluble in water, and drip in three times,
Regulate pH value with saturated solution of sodium bicarbonate after dropping is 8-9 every time.After stirring 1 hour, reactant mixture is moved into thoroughly
Analysis bag, after dialysing 48 hours in water, lyophilization obtains product V.
Step f, is dissolved in 0.42g gold chloride in 20mL ultra-pure water, is heated to boiling, is rapidly added 1.00g sodium citrate,
It is cooled to room temperature after reacting 5 minutes, stops after continuing stirring 0.5 hour, obtain nano gold sol product VI.
Step g, is dissolved in 0.2g product V in 2mL DMSO, and drips 10mL concentration 0.001mol/L product VI,
Moving in 3500Da bag filter after reacting 12 hours under room temperature, dialyse 24 hours in ultra-pure water, rotation is evaporated off major part
After water under 3000 revs/min of revolutions centrifugation 30 minutes, take upper solution concentrate postlyophilization obtain end product.
Embodiment 4
Step a, is dissolved in polysuccinimide 1.0g in 5mL DMF solvent, and puts in 100ml there-necked flask, stirs
Mix, logical nitrogen protection, add 0.2g1-nitrine propylamine after being warming up to 60 DEG C, after reacting 24 hours, stop heating.Will reaction
Mixture is transferred to the bag filter that molecular cut off is 3500 and dialyses in DMF 48 hours, and rotary evaporation is removed DMF and obtained
Darkorange thick liquid, obtains product I after drying under reduced pressure.
Step b, is dissolved in 1.25g product I in 5mL DMF solvent, and logical nitrogen protection, stirring adds1.25g to amino Phenylmercaptan., 1.32g DIPEA, reactant mixture was transferred to molecular cut off and is after 24 hours by 60 DEG C of reactions
Dialysing 48 hours in ultra-pure water in 3500 bag filters, rotary evaporation is removed major part water postlyophilization and is obtained product II.
Step c, takes 1.0g product II and 3.90g N2-(4-alkynyl)-diethylenetriamines-four tert-butyl ester is dissolved in 5mL tetrahydrochysene furan
In muttering, add freshly prepared 1mol L-1Sodium ascorbate and each 1mL of copper sulphate pentahydrate aqueous solution, react at room temperature
Add 10mL water, 10mL dichloromethane after 2 hours, after stirring 2 minutes, be transferred to separatory funnel, retain organic layer, in
After dialysing 24 hours in dichloromethane, rotary evaporation removes dichloromethane, obtains product III after drying under reduced pressure.
Step d, is dissolved in 3.0g product III in 5mL dichloromethane, stirring, is slowly added dropwise 2mL trifluoroacetic acid under room temperature,
Room temperature reaction stopped after 24 hours, after rotation is evaporated off dichloromethane and trifluoroacetic acid, added 10mL ether ultrasonic disperse 10 points
Clock, obtains white solid powder, then washs three times with absolute ether, obtains product IV after drying under reduced pressure.
Step e, is dissolved in 2.5g product IV in 5mL ultra-pure water, by 0.7g GdCl3Soluble in water, and drip in three times,
Regulate pH value with saturated solution of sodium bicarbonate after dropping is 8-9 every time.After stirring 1 hour, reactant mixture is moved into thoroughly
Analysis bag, after dialysing 48 hours in water, lyophilization obtains product V.
Step f, is 2 × 10 by 25mL concentration with vigorous stirring in cryosel is bathed-3mol·L-1 Silver nitrate solutionIt is added drop-wise to
25mL concentration is 8 × 10-3mol·L-1In sodium borohydride aqueous solution, obtain the Nano silver grain hydrosol after reacting 30 minutes and produce
Thing VI.
Step g, is dissolved in 0.2g product V in 2mL DMSO, and drips 10mL concentration 0.001mol/L product VI,
Moving in 3500Da bag filter after reacting 12 hours under room temperature, dialyse 24 hours in ultra-pure water, rotation is evaporated off major part
After water under 3000 revs/min of revolutions centrifugation 30 minutes, take upper solution concentrate postlyophilization obtain end product.
Claims (9)
1. noble metal/paramagnetic metal composite nanoparticle, by noble metal nano particles, organic bonding units and paramagnetic gold
Belonging to composition, its preparation method comprises the following steps:
(1) polysuccinimide is dissolved in DMF (DMF), is warming up under nitrogen protection and stirring
30～65 DEG C, being subsequently adding compound A, stop heating after 24-48 hour, reactant mixture steams through dialysis, rotation, dried
To product I；Described compound A is 1-alkyl azide amine, and wherein the carbon atom number of alkyl is at 2～6；
(2) product I is dissolved in DMF, nitrogen protection and the lower dropping compound B of stirring and catalyst n, N-
Diisopropylethylamine, in 30～80 DEG C reaction 24-48 hour after stop heating, reactant mixture through dialysis, rotation steam, be dried to obtain
Product II；Described compound B is p-aminophenyl thiophenol or L-cysteine hydrochloride or Mercaptamine；
(3) by product II and the N shown in formula (I)2-(4-alkynyl)-diethylenetriamines-four tert-butyl ester is dissolved in oxolane, then adds
Enter the sodium ascorbate of brand-new and the aqueous solution of copper sulphate pentahydrate, at room temperature extract and separate organic layer after reaction 2-4 hour, then
Steam through dialysis, rotation, be dried to obtain product III；
(4) product III is dissolved in dichloromethane, is slowly added dropwise trifluoroacetic acid under stirring, finishes room temperature reaction 24-48 hour
Rear stopping, rotation is evaporated off dichloromethane and trifluoroacetic acid, adds ether ultrasonic disperse, and separating, washing, drying obtains product
IV；
(5) product IV being dissolved in ultra-pure water, the aqueous solution of dropping compound C, a complete regulation pH value, to 8-9, then stirs
Mixing 1-2 hour, reactant mixture is through dialysing, being dried to obtain product V；Described compound C is selected from paramagnetic lanthanide series metal chloride；
(6) preparation gold or Nano silver grain；
(7) product V is dissolved in dimethyl sulfoxide (DMSO), and adds step (6) freshly prepd gold or Nano silver grain,
Reacting after 12-24 hour under room temperature, reactant mixture steams through dialysis, rotation, it is multiple to be dried to obtain end product noble metal/paramagnetic metal
Close nanoparticle.
2. noble metal/paramagnetic metal composite nanoparticle as claimed in claim 1, it is characterised in that: in step (1), poly-
Butanimide is 1:0.2～0.5 with the molar ratio of compound A.
3. noble metal/paramagnetic metal composite nanoparticle as claimed in claim 1, it is characterised in that: in step (2), produce
Thing I, compound B, N, the molar ratio of N-diisopropylethylamine is 1:0.8～0.5:0.8～0.5.
4. noble metal/paramagnetic metal composite nanoparticle as claimed in claim 1, it is characterised in that: in step (3), produce
Thing II and N2-(4-alkynyl)-diethylenetriamines-four tert-butyl ester, sodium ascorbate, the molar ratio of copper sulfate are 1:0.2～0.5:
0.2～0.5:0.2～0.5.
5. noble metal/paramagnetic metal composite nanoparticle as claimed in claim 1, it is characterised in that: in step (4), produce
Thing III is 1:4～8 with the molar ratio of trifluoroacetic acid.
6. noble metal/paramagnetic metal composite nanoparticle as claimed in claim 1, it is characterised in that: in step (5), produce
The molar ratio of thing IV and compound C is 1:1～2.
7. noble metal/paramagnetic metal composite nanoparticle as claimed in claim 1, it is characterised in that: in step (7), produce
Thing V is 1:8～32 with the molar ratio of the nano noble metal particles in nano-noble metal colloid solution.
8. noble metal/paramagnetic metal the composite nanoparticle as claimed in claim 1 application in preparing MRI enhancing contrast medium.
9. noble metal/paramagnetic metal the composite nanoparticle as claimed in claim 1 application in preparing CT enhancing contrast medium.
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| CN104028181A (en) * | 2014-04-24 | 2014-09-10 | 温州大学 | Precious metal/paramagnetic metal composite nanoparticle with core-shell structure and application thereof |
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| TW201212942A (en) * | 2010-09-28 | 2012-04-01 | Univ Nat Cheng Kung | CT/MRI dual modality molecular imaging contrast agent and method for manufacturing the same |
| KR101721570B1 (en) * | 2011-06-22 | 2017-03-30 | 한화케미칼 주식회사 | MRI Contrast Agent for Lymph Node Based on Iron Oxide Nanoparticles and Method for Imaging Lymph Node Using The Same |
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|---|---|---|---|---|
| CN101620910A (en) * | 2008-07-01 | 2010-01-06 | 中国科学院成都有机化学有限公司 | Preparation method and application of core-shell magnetic/gold nanocomposite particles |
| CN104028181A (en) * | 2014-04-24 | 2014-09-10 | 温州大学 | Precious metal/paramagnetic metal composite nanoparticle with core-shell structure and application thereof |
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| Title |
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