CN104028181A - Precious metal/paramagnetic metal composite nanoparticle with core-shell structure and application thereof - Google Patents
Precious metal/paramagnetic metal composite nanoparticle with core-shell structure and application thereof Download PDFInfo
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Abstract
The invention discloses a precious metal/paramagnetic metal composite nanoparticle with a core-shell structure and application thereof. A preparation method for the precious metal/paramagnetic metal composite nanoparticle comprises the following steps: (a) preparing a precious metal nanoparticle with a particle size of 5 to 50 nm, wherein the precious metal is gold or silver; (b) taking a compound A containing a mercapto group and an amino group, allowing the precious metal nanoparticle to react with the compound A so as to obtain a product a and then allowing the product a to react with methyl acrylate so as to obtain a product b; (c) taking a compound C containing an azido group and an amino group and reacting the product obtained in the step (b) with the compound C so as to obtain an azido-surface-modified precious metal nanoparticle; (d) subjecting the azido-surface-modified precious metal nanoparticle prepared in the step (c) and a micromolecular ligand containing an alkynyl group to the Clicker reaction so as to obtain a product d; and (e) reacting the product d with a chloride of a paramagnetic metal so as to obtain the composite nanoparticle. The precious metal/paramagnetic metal composite nanoparticle can be used as an MRI and CT enhancement contrast agent.
Description
Technical field
The present invention relates to a kind of noble metal/paramagnetic metal composite nanoparticle and the application thereof with nucleocapsid structure of field of nanometer technology, especially strengthen the application of contrast medium as MRI and CT.
Technical background
The particularity of metal-organic composite nano particle, has determined the Chemical Physics performance that it is unique and has been widely used in the fields such as optical, electrical, catalysis, immune detection.Nearest research shows, magnetic nano-particle can improve the electron density of paramagnetic metal chelate, accelerates the exchange rate of paramagnetic metal and ambient water molecule.Having of noble metal nano particles is beneficial to the outer-shell electron rotation of accelerating paramagnetic metal ion, can be used for improving the relaxation rate of paramagnetic metal.Moriggi has reported that containing in the compound system that 201 gold nanoclusters and 56 paramagnetic metals coexist, relaxation rate can be increased to 3000mM
-1s
-1.In addition, Manus has reported that Nano diamond is to improving the effect of paramagnetic metal contrast preparation relaxation rate.But they all adopt the relaxation rate of the doped aggregate cluster enhancing paramagnetic metal of closs packing configuration, the composite nanoparticle complex structure obtaining like this, preparation cost is high, and biocompatibility is poor, unfavorable to metabolism.The present invention strengthens the relaxation rate of paramagnetic metal with the noble metal nano quantum dot of the regular arrangement of single or multiple lift.This composite nanoparticle adopts core-shell configuration, and noble metal nano particles distributes with quantum dot, and preparation cost is low, and particle size is controlled, is expected to for nuclear magnetic resonance (MRI) molecular imaging and computed tomography (CT) contrast-enhancing agent.At present, the research based on this respect there is not yet report.
Summary of the invention
The object of the present invention is to provide a kind of noble metal nano particles distributing with quantum dot and paramagnetic metal with same composite nanoparticle and the application thereof of depositing of nucleocapsid structure, this composite nanoparticle forms noble metal and paramagnetic metal link by organic bonding unit, its compound with regular structure, relaxation rate are high, can be used as MRI and CT and strengthen contrast medium.
Novel noble metal/paramagnetic metal composite nanoparticle involved in the present invention is made up of noble metal nano particles, organic bonding unit and paramagnetic metal, and it is taking noble metal (gold or silver) as core, the nucleocapsid structure that paramagnetic metal is shell.Noble metal distributes with quantum dot, and and paramagnetic metal between by organic bonding unit link.In organic bonding unit, containing sulfydryl, can form Au-S key or Ag-S key with gold or biochemical reaction of silver hair.In addition, organic bonding also contains azido group in unit, can with react containing there is " Click " between the little molecule ligand of alkynyl, form penta azacyclo, link little molecule ligand, little molecule ligand and paramagnetic metal generation complexation reaction, thereby introducing paramagnetic metal.Therefore, can be by noble metal and paramagnetic metal link by organic bonding unit.
Noble metal/paramagnetic metal composite nanoparticle with nucleocapsid structure of the present invention, its preparation method comprises the following steps:
(a) prepare the noble metal nano particles that particle diameter is 5-50nm; Described noble metal is gold or silver-colored;
(b) get compd A, contain sulfydryl and amino in the structure of described compd A, make the sulfydryl generation chemical reaction in noble metal nano particles and compd A prepared by step (a) form M-S-key, M is Au or Ag, obtains product a; Make again the amino in product a react formation with methyl acrylate
key, obtains product b;
(c) get Compound C, in the structure of described Compound C, contain azido group and amino, make to contain in the product of step (b)
in ester group react formation with the amino in Compound C
key, the noble metal nano particles of azido group that obtained finishing;
(d) get modification that step (c) makes azido group noble metal nano particles with carry out Click containing the little molecule ligand of alkynyl and react, obtain product d;
(e) product d is reacted with the chloride of paramagnetic metal, after reaction finishes, obtain having noble metal/paramagnetic metal composite nanoparticle of nucleocapsid structure through separation and purification.
In described step (a), the preparation method of gold or Nano silver grain is conventional reduction method, those skilled in the art can complete preparation according to prior art, for example can be prepared as follows: appropriate precious metal chemical complex (chlorauride, perchloric acid gold, silver nitrate etc.) is dissolved in ultra-pure water, be heated to add rapidly appropriate natrium citricum or sodium borohydride after boiling, react and be cooled to room temperature after 5-10 minute, continue stirring and stop after 0.5-1 hour, obtain noble metal nano colloidal solution.Wherein the mol ratio of precious metal chemical complex and natrium citricum or sodium borohydride is 1:4～8.There is certain rule the particle size of noble metal nano particles and its finishing point position, and in general particle diameter is less, and specific area is larger, and adorned some figure place is just more.The point figure place of Au nanoparticle surface has four at least.Adorned some figure place of noble metal nano particles is also relevant with the volume size of trim.The volume of trim is larger, sterically hindered stronger, and the possibility in modification is less.
Described step (b) is specifically according to carrying out as follows: get noble metal nano particles methyl alcohol prepared by step (a) and disperse; add compd A; under the protection of nitrogen; stir lucifuge reaction 24-48h in 0-20 DEG C of constant temperature; reactant mixture obtains product a after dialysing, revolving steaming; product a again in methanol solvate with methyl acrylate room temperature reaction 24-48 hour, dialysis obtains product b after purifying.
In described step (b), the molar ratio of noble metal nano particles, compd A, methyl acrylate is at 1:4-8:8-16.
Further, described step (b) also comprises step (b '): get and contain sulfydryl and amino compd A ', make to contain in product b
in ester group and compd A ' in amino react formation
key, make the sulfydryl containing in products therefrom react again generation-S-M key with noble metal nano particles, then get and contain sulfydryl and amino compd A "; products therefrom is continued and compd A " in the sulfydryl that contains react formation-S-M-S-, then make the amino containing in product react formation with methyl acrylate
obtain product b '.Described compd A, compd A ' and compd A " can be the same or different, independent preferably from one of following separately: 2-sulfydryl-5-aminobenzimidazole or 3-sulfydryl-PABA or mercaptoethylmaine.The operation of step b ' as required can be repeatedly, to form the product with multilayer noble metal nano particles.
Described step b ' is specifically according to carrying out as follows: product b with contain sulfydryl and amino compd A ' room temperature reaction 12～24 hours in methyl alcohol, dialysis is purified; Products therefrom again with noble metal nano particles in pure water under nitrogen protection room temperature reaction 1～3 hour, dialysis is purified; Then make products therefrom and contain sulfydryl and amino compd A " in methyl alcohol in room temperature reaction 12～24 hours, dialysis is purified; Products therefrom again in methyl alcohol with methyl acrylate room temperature reaction 24～48 hours, dialysis is purified and is obtained product b '.
Described step (c) is specifically according to carrying out as follows: get product and the Compound C that step (b) makes and be dissolved in methanol solvate, under room temperature, react 24-48h, after reaction finishes, remove desolventizing by rotary evaporation, then in methyl alcohol, unreacted Compound C is removed in dialysis, the noble metal nano particles of azido group that obtained finishing.The preferred 1-alkyl azide of described Compound C amine, wherein the carbon atom number of alkyl is at 3～5, the such as homologue such as 1-nitrine propylamine, 1-nitrine butylamine.
In described step (c), the product that step (b) makes and Compound C are that 1:2～8 feed intake according to ester group and amino mol ratio.
Described step (d) is specifically according to carrying out as follows: get modification that step (c) makes the noble metal nano particles of azido group be dissolved in N with the little molecule ligand containing alkynyl, in dinethylformamide, add copper sulphate/sodium ascorbate to carry out Click reaction (preferred reaction 12～24 hours) as catalyst in room temperature, gained reactant mixture obtains product d through separating-purifying.The described little molecule ligand containing alkynyl is N
2-(4-alkynyl)-diethylenetriamines-tetraacethyl, its structure is as follows:
In described step (d), the noble metal nano particles of having modified azido group is that 1:1-2 feeds intake with the little molecule ligand containing alkynyl according to the mol ratio of azido and alkynyl, and the molar ratio that contains the little molecule ligand of alkynyl and copper sulphate, sodium ascorbate is 1:1:1.
In described step (d), the preferred gadolinium of paramagnetic metal, reaction is preferably carried out in room temperature, preferably 1～3 hour reaction time.
In described step (e), product d carries out with muriatic the reaction in the mixed solvent of dimethyl sulfoxide (DMSO) and water of paramagnetic metal, and product d and paramagnetic metal are that 1:2～4 feed intake according to the mol ratio of little molecule ligand and paramagnetic metal.
Noble metal/paramagnetic metal composite nanoparticle with nucleocapsid structure of the present invention, its compound with regular structure, relaxation rate are high, can be used as MRI and CT and strengthen contrast medium.
Compared with prior art, beneficial effect of the present invention is: the present invention has prepared a kind of noble metal/paramagnetic metal composite nanoparticle with nucleocapsid structure, and its compound with regular structure, relaxation rate are high, can be used as good MRI and CT and strengthens contrast medium.
Brief description of the drawings
Fig. 1 is the infrared spectrogram of gold/gadolinium composite nanoparticle of the individual layer nucleocapsid structure that makes of embodiment 1.
Fig. 2 is the transmission electron microscope picture of gold/gadolinium composite nanoparticle of the individual layer nucleocapsid structure that makes of embodiment 1.
Fig. 3 is the planar structure schematic diagram of gold/gadolinium composite nanoparticle of two-layer nucleocapsid structure.
1.00,0.50,0.25,0.125,0.0625,0.0mmolL Fig. 4 is gold/gadolinium nano particle (1) and nuclear magnetic resonance (MRI) image of commercial Magnevist Solution (2) in pure water of different gadolinium ion concentration, and sample concentration is followed successively by from top to bottom:
-1.
Fig. 5 is gold/gadolinium nano-particle compound of variable concentrations computed tomography (CT) image in pure water, and sample concentration is followed successively by 1.00,0.50,0.25,0.125,0.0625 from left to right, 0.0mmolL
-1.
Detailed description of the invention
Provide following instance in order further to set forth spy of the present invention.Obviously embodiments of the present invention are not limited to following embodiment.
The little molecule ligand that the embodiment of the present invention is used is N
2-(4-alkynyl)-diethylenetriamines-tetraacethyl.
Embodiment 1
Step a: under 25 DEG C of stirrings, be 0.03molL to adding 3mL concentration in 100mL deionized water
-1sodium citrate solution, heat while stirring to boiling.After solution boiling, adding rapidly 1mL concentration is 0.02molL
-1chlorogold solution and heat micro-boiling and stir after 5 minutes, stop stirring and heating, be cooled to room temperature, obtain particle diameter and be distributed as the golden nanometer particle hydrosol of 5-50nm;
Step b: get the golden nanometer particle hydrosol 10mL methyl alcohol that 2mL step a makes and again disperse, add 5g2-sulfydryl-5-aminobenzimidazole, under nitrogen protection, in 0 DEG C of lucifuge stirring reaction 24 hours, the dialysis membrane that reactant mixture is 3500Da through molecular cut off reacts 48 hours with under 20mL methyl acrylate room temperature after steaming in dialysing in methyl alcohol, revolving and removing most of methanol solvate, and the dialysis membrane that reactant mixture is 3500Da through molecular cut off dialysis in methyl alcohol, concentrated by rotary evaporation, freeze-drying obtain product b;
Product b detects through Fourier infrared spectrograph the compounds containing thiol groups that shown golden nanometer particle finishing, sees Fig. 1; Transmission electron microscope shows that the particle diameter of product b is 80nm left and right, sees Fig. 2.
Step c: product b is put in 10mL methyl alcohol, then add 30mL1-nitrine propylamine, under room temperature, react the dialysis membrane that mixture is 3500Da through molecular cut off dialysis in methyl alcohol, concentrated by rotary evaporation, freeze-drying, the single layer of gold nano particle of azido group that obtained finishing 12 hours;
Steps d: get modification that 0.1g step c makes single layer of gold nano-complex particle and the 2g of azido group be dissolved in 5mL N containing the little molecule ligand of alkynyl, in dinethylformamide, at copper sulphate/sodium ascorbate (mol ratio 1:1, each 0.1mol) there are lower room temperature reaction 6 hours, chloroform/water for reactant mixture (volume ratio 1:1) extract and separate, collect organic solvent part, and carry out Ultrafiltration Purifying, freeze-drying obtains product d;
Step e: product d reacts 2 hours in 15mL dimethyl sulfoxide (DMSO)/water (volume ratio 1:2) mixed solution with 5g gadolinium chloride again, freeze-drying after reactant mixture Ultrafiltration Purifying, obtains gold/gadolinium composite nanoparticle of individual layer nucleocapsid structure.
Embodiment 2 (with embodiment 1, with Nano silver grain replacement golden nanometer particle)
Step a: under vigorous stirring in cryosel bathe in by 25mL2 × 10
-3m liquor argenti nitratis ophthalmicus is added drop-wise to 25mL8 × 10
-3in M sodium borohydride aqueous solution, time for adding was controlled within 30 minutes.With adding of silver nitrate, reducing agent water liquid color becomes light yellowly from colourless gradually, finally becomes brown color, has obtained the Nano silver grain hydrosol, and particle diameter is distributed in 5～50nm.
Step b: the Nano silver grain hydrosol of getting 2mL step a gained; again after disperseing with 50mL methyl alcohol; add 5g2-sulfydryl-5-aminobenzimidazole; under the protection of nitrogen; stir lucifuge reaction 48 hours in 20 DEG C of constant temperature; the dialysis membrane that reactant mixture is 3500Da through molecular cut off is put in 10mL methanol solution after dialysis in methyl alcohol, concentrated by rotary evaporation, freeze-drying, then reacts 48 hours reactant mixture dialysis purifying with under 20mL methyl acrylate room temperature.
Step c: the product after step b purifying is dissolved in 10ml methyl alcohol, then adds 30mL1-nitrine propylamine, react under room temperature 12 hours, freeze-drying after mixture dialysis purifying, the single-layer silver nanoparticle of azido group that obtained finishing.
Steps d: get modification that 0.1g step c makes single-layer silver nanoparticle compound and the 2g of azido group be dissolved in 5mL N containing the little molecule ligand of alkynyl, in dinethylformamide, under the each 0.1mol of copper sulphate/sodium ascorbate exists, room temperature reaction 12 hours, the each 5mL extract and separate of chloroform/water for reactant mixture, collect organic solvent part, and carry out Ultrafiltration Purifying, freeze-drying obtains product d.
Step e: product d reacts 2 hours in the mixed solvent of 5mL dimethyl sulfoxide (DMSO)/10mL water composition with 10g gadolinium chloride again, freeze-drying after reactant mixture Ultrafiltration Purifying, obtains silver/gadolinium composite nanoparticle of individual layer nucleocapsid structure.
Embodiment 3
Step a, under 25 DEG C of stirrings, is 0.03molL to adding 3mL concentration in 100mL deionized water
-1sodium citrate solution, heat while stirring to boiling.After solution boiling, adding rapidly 1mL concentration is 0.02molL
-1chlorogold solution and heat micro-boiling and stir after 5 minutes, stop stirring and heating is cooled to room temperature, obtain particle diameter and be distributed as the golden nanometer particle hydrosol of 5-50nm.
Step b, getting the golden nanometer particle hydrosol 10mL methyl alcohol that 2mL step a makes disperses again, add 5g3-sulfydryl-PABA, under nitrogen protection, in 0 DEG C of lucifuge stirring reaction 24 hours, the dialysis membrane that reactant mixture is 3500Da through molecular cut off is dialysed in methyl alcohol, revolve after most of methanol solvate is removed in steaming and react 48 hours with under 20mL methyl acrylate room temperature, after reactant mixture dialysis purifying, in 10mL methanol solvate, react 24 hours again with under 5g3-sulfydryl-PABA room temperature, dialysis after purifying again with the 5mL golden nanometer particle hydrosol in pure water under nitrogen protection in room temperature reaction 24 hours, dialysis purifying obtains two-layer divergent shape golden nanometer particle compound.Compound is continued and 10g2-sulfydryl-5-aminobenzimidazole room temperature reaction 24 hours in 20mL methyl alcohol, after dialysis purifying again with 20mL methyl acrylate in 20mL methyl alcohol in room temperature reaction 48 hours, after dialysis purifying, freeze-drying obtains product b.
Step c, product b reacts 24 hours in 20mL methyl alcohol with 10g1-nitrine butylamine under room temperature, freeze-drying after reactant mixture dialysis purifying, obtains product c, i.e. finishing the two-layer golden nanometer particle of azido group.
Steps d: get 0.1g product c and 4g and be dissolved in 15mL N containing the little molecule ligand of alkynyl, in dinethylformamide, under the each 0.1mol of copper sulphate/sodium ascorbate exists, room temperature reaction 12 hours, 10mL chloroform, 10mL water mixed solution extract and separate for reactant mixture, collect organic solvent part, rotary evaporation is removed after organic solvent, obtains product d.
Step e, product d reacts 4 hours under room temperature in the mixed solvent of 10mL dimethyl sulfoxide (DMSO), 20mL water composition with 10g gadolinium chloride again, and freeze-drying after reactant mixture Ultrafiltration Purifying obtains gold/gadolinium composite nanoparticle of two-layer nucleocapsid structure.Embodiment 4 (with embodiment 3, with Nano silver grain replacement golden nanometer particle)
Step a: under vigorous stirring in cryosel bathe in by 25mL2 × 10
-3m liquor argenti nitratis ophthalmicus is added drop-wise to 25mL8 × 10
-3in M sodium borohydride aqueous solution, time for adding was controlled within 30 minutes.With adding of silver nitrate, reducing agent water liquid color becomes light yellowly from colourless gradually, finally becomes brown color, has obtained the Nano silver grain hydrosol, and its particle diameter is distributed in 5～50nm.
Step b: the Nano silver grain hydrosol of getting 2mL step a gained, again after disperseing with 50mL methyl alcohol, add 5g3-sulfydryl-PABA, under the protection of nitrogen, stir lucifuge reaction 48 hours in 20 DEG C of constant temperature, the dialysis membrane that reactant mixture is 3500Da through molecular cut off is dialysed in methyl alcohol, revolve and steam except desolventizing, after freeze-drying, put in 10mL methanol solution, then add 20mL ethyl acrylate, under room temperature, react 24 hours, after reactant mixture dialysis purifying, in 10mL methanol solvate, react 24 hours again with under 5g3-sulfydryl-PABA room temperature, after dialysis again with the 5mL Nano silver grain hydrosol in 20mL pure water under nitrogen protection room temperature reaction 24 hours, obtain two-layer divergent shape Nano silver grain compound.Continued under room temperature, to react 24 hours in 20mL methyl alcohol with 10g2-sulfydryl-5-aminobenzimidazole, after dialysis purifying, react 24 hours with 20mL methyl acrylate in 20mL methyl alcohol under room temperature again, after dialysis purifying, freeze-drying obtains product b.
Step c, product b reacts 12 hours in 30mL methyl alcohol with 10g1-nitrine butylamine under room temperature, freeze-drying after reactant mixture dialysis purifying, obtains product c, i.e. finishing the two-layer Nano silver grain of azido group.
Steps d: get modification that 0.1g step c makes two-layer Nano silver grain compound and the 5g of azido group be dissolved in 20mL N containing the little molecule ligand of alkynyl, in dinethylformamide, room temperature reaction 12 hours under the each 0.1mol of copper sulphate/sodium ascorbate exists, the each 5ml extract and separate of chloroform/water for reactant mixture, collect organic solvent part, rotary evaporation is removed after organic solvent, obtains product d.
Step e, product d reacts under room temperature 2 hours in 10ml water mixed solution with 10g gadolinium chloride again, and freeze-drying after reactant mixture Ultrafiltration Purifying obtains silver/gadolinium composite nanoparticle of two-layer nucleocapsid structure.
Embodiment 5
The end product that embodiment 1 is obtained be configured to variable concentrations the aqueous solution (1.00,0.50,0.25,0.125,0.0625,0.0mmolL
-1).Then be placed in small test tube, respectively at testing imaging effect in NMR imaging instrument and computed tomographic scanner.Result shows, this composite nanoparticle possesses MRI and strengthens effect (as Fig. 4), and CT imaging effect (as Fig. 5).Its relaxation rate is higher 10 times than commercial Magnevist Solution parenteral solution (Beilu Pharmaceutical Industry Co., Ltd., Beijing) contrast preparation.
The application of novel noble metal/paramagnetic metal composite nanoparticle involved in the present invention, refers to the application in biomedical imaging field.Its application comprises the Real-Time Evaluation that molecular imaging, early diagnosis of tumor, gene imaging expression, drug disposition transmit.
Above-described embodiment is only preference of the present invention, is not used for limiting the present invention, and all within principle of the present invention, any amendment, variation, accommodation or the alternative made, all within protection scope of the present invention.
Claims (9)
1. noble metal/paramagnetic metal composite nanoparticle with nucleocapsid structure, its preparation method comprises the following steps:
(a) prepare the noble metal nano particles that particle diameter is 5-50nm; Described noble metal is gold or silver-colored;
(b) get and contain sulfydryl and amino compd A, make noble metal nano particles prepared by step (a) react formation M-S-key with the sulfydryl in compd A, M is Au or Ag, obtains product a; Make again the amino in product a react formation with methyl acrylate
obtain product b;
(c) get and contain azido group and amino Compound C, make to contain in the product of step (b)
in ester group react formation with the amino in Compound C
key, the noble metal nano particles of azido group that obtained finishing;
(d) get modification that step (c) makes azido group noble metal nano particles with carry out Click containing the little molecule ligand of alkynyl and react, obtain product d;
(e) product d is reacted with the chloride of paramagnetic metal, after reaction finishes, obtain having noble metal/paramagnetic metal composite nanoparticle of nucleocapsid structure through separation and purification.
2. noble metal/paramagnetic metal composite nanoparticle with nucleocapsid structure as claimed in claim 1, is characterized in that described step b also comprises step b': get and contain sulfydryl and amino compd A ', make to contain in product b
in ester group and compd A ' in amino react formation
key, the noble metal nano particles that the sulfydryl containing in products therefrom is made with step (a) again reacts generation-S-M key, then get and contain sulfydryl and amino compd A "; products therefrom is continued and compd A " in the sulfydryl that contains react formation-S-M-S-, then make the amino containing in products therefrom react formation with methyl acrylate
obtain product b '.
3. noble metal/paramagnetic metal composite nanoparticle with nucleocapsid structure as claimed in claim 2, is characterized in that: using the product of step b ' as raw material, the repeatedly operation of repeating step b ', to form the product with multilayer noble metal nano particles.
4. noble metal/paramagnetic metal the composite nanoparticle with nucleocapsid structure as described in one of claim 1～3, is characterized in that: described compd A is selected from one of following: 2-sulfydryl-5-aminobenzimidazole, 3-sulfydryl-PABA, mercaptoethylmaine.
5. noble metal/paramagnetic metal composite nanoparticle as claimed in claim 2 or claim 3 with nucleocapsid structure, is characterized in that: described compd A, compd A ' and compd A " be independently selected from separately one of following: 2-sulfydryl-5-aminobenzimidazole, 3-sulfydryl-PABA, mercaptoethylmaine.
6. noble metal/paramagnetic metal the composite nanoparticle with nucleocapsid structure as described in one of claim 1～3, is characterized in that: described Compound C is 1-alkyl azide amine, and wherein the carbon atom number of alkyl is at 3～5.
7. noble metal/paramagnetic metal the composite nanoparticle with nucleocapsid structure as described in one of claim 1～3, is characterized in that the described little molecule ligand containing alkynyl is N
2-(4-alkynyl)-diethylenetriamines-tetraacethyl, its structure is as follows:
8. noble metal/paramagnetic metal composite nanoparticle with nucleocapsid structure as claimed in claim 1 strengthens the application of contrast medium as MRI.
9. noble metal/paramagnetic metal composite nanoparticle with nucleocapsid structure as claimed in claim 1 strengthens the application of contrast medium as CT.
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| CN109548393A (en) * | 2018-11-09 | 2019-03-29 | 南京理工大学 | A kind of narrow frequency range responding microwave material and preparation method thereof |
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| CN113912885B (en) * | 2021-11-26 | 2022-04-26 | 嘉兴高正新材料科技股份有限公司 | Low-temperature-resistant PVDF (polyvinylidene fluoride) film for photovoltaic back plate and preparation method thereof |
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