CN104028181B - There is noble metal/paramagnetic metal composite nanoparticle and the application thereof of nucleocapsid structure - Google Patents
There is noble metal/paramagnetic metal composite nanoparticle and the application thereof of nucleocapsid structure Download PDFInfo
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Abstract
The invention discloses a kind of noble metal/paramagnetic metal composite nanoparticle and the application thereof with nucleocapsid structure, the preparation method of described noble metal/paramagnetic metal composite nanoparticle comprises: (a) prepares the noble metal nano particles that particle diameter is 5-50nm; Described noble metal is gold or silver-colored; B () gets containing sulfydryl and amino compd A, noble metal nano particles and compd A are reacted, obtains product a; Make product a and methyl acrylate react again, obtain product b; C () gets containing azido group and amino Compound C, the product of step (b) and Compound C are reacted, obtains the noble metal nano particles of finishing azido group; D () is got the obtained product of step (c) and is carried out Click reaction with the smaller ligand containing alkynyl, obtain product d; E the chloride of product d and paramagnetic metal reacts by (), obtain described composite nanoparticle.Described noble metal/paramagnetic metal composite nanoparticle, can be used as MRI and CT and strengthens contrast medium.
Description
Technical field
The present invention relates to a kind of noble metal with nucleocapsid structure/paramagnetic metal composite nanoparticle and application thereof 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, determines the Chemical Physics performance of its uniqueness and is 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 chelates, accelerates the exchange rate of paramagnetic metal and surrounding water molecules.The outer-shell electron being beneficial to quickening paramagnetic metal ion that has of noble metal nano particles rotates, and can be used for the relaxation rate improving paramagnetic metal.Moriggi reports in the compound system coexisted containing 201 gold nanoclusters and 56 paramagnetic metals, and relaxation rate can be increased to 3000mM
-1s
-1.In addition, Manus reports Nano diamond to the effect improving paramagnetic metal contrast preparation relaxation rate.But they all adopt the doped aggregate cluster of closs packing configuration to strengthen the relaxation rate of paramagnetic metal, and the composite nanoparticle complex structure obtained like this, preparation cost is high, poor biocompatibility, 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 structure copolymer 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, based on the research of this respect, there is not been reported.
Summary of the invention
The object of the present invention is to provide a kind of composite nanoparticle of depositing together with nucleocapsid structure with noble metal nano particles and the paramagnetic metal of quantum dot distribution and application thereof, noble metal and paramagnetic metal link are formed by organic bonding units by this composite nanoparticle, 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 units and paramagnetic metal, and it is that for core, paramagnetic metal is the nucleocapsid structure of shell with noble metal (gold or silver).Noble metal distributes with quantum dot, and and is linked by organic bonding units between paramagnetic metal.Containing sulfydryl in organic bonding units, Au-S key or Ag-S key can be formed with gold or biochemical reaction of silver hair.In addition, also containing azido group in organic bonding units, can and the smaller ligand containing alkynyl between there is " Click " and react, form penta azacyclo, link smaller ligand, smaller ligand and paramagnetic metal generation complexation reaction, thus introducing paramagnetic metal.Therefore, can by noble metal and paramagnetic metal link by organic bonding units.
Noble metal/paramagnetic metal the composite nanoparticle with nucleocapsid structure of the present invention, its preparation method comprises the following steps:
A () prepares the noble metal nano particles that particle diameter is 5-50nm; Described noble metal is gold or silver-colored;
B () gets compd A, containing sulfydryl and amino in the structure of described compd A, the sulfydryl generation chemical reaction in noble metal nano particles prepared by step (a) and compd A forms M-S-key, and M is Au or Ag, obtains product a; Make the amino in product a and methyl acrylate react again to be formed
key, obtains product b;
C () gets Compound C, containing azido group and amino in the structure of described Compound C, make to contain in the product of step (b)
in ester group and amino in Compound C carry out reaction and formed
key, obtains the noble metal nano particles of finishing azido group;
D () is got the obtained noble metal nano particles having modified azido group of step (c) and is carried out Click reaction with the smaller ligand containing alkynyl, obtain product d;
E () makes the chloride of product d and paramagnetic metal react, obtain having the noble metal/paramagnetic metal composite nanoparticle of nucleocapsid structure after reaction terminates 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, such as can be prepared as follows: appropriate precious metal chemical complex (chlorauride, perchloric acid gold, silver nitrate etc.) is dissolved in ultra-pure water, proper amount of sodium citrate or sodium borohydride is added rapidly after being heated to boiling, react and be cooled to room temperature after 5-10 minute, continue to stir after 0.5-1 hour and stop, obtaining 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 an adorned figure place is more.The point figure place of Au nanoparticle surface has four at least.Noble metal nano particles adorned some figure place 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; lucifuge reaction 24-48h is stirred 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 purifying after obtain product b.
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 containing sulfydryl and amino compd A ', make to contain in product b
in ester group and compd A ' in amino react and formed
key, the sulfydryl contained in products therefrom is reacted with noble metal nano particles again and generates-S-M key, then get containing sulfydryl and amino compd A "; products therefrom is continued and compd A " in the sulfydryl that contains react formation-S-M-S-, then the amino that contains in product and methyl acrylate are reacted formed
obtain product b '.Described compd A, compd A ' and compd A " can be the same or different, separately independent preferred from one of following: 2-sulfydryl-5-aminobenzimidazole or 3-sulfydryl-PABA or mercaptoethylmaine.The operation of step b ' as required can 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 containing 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 room temperature reaction 1 ~ 3 hour under nitrogen protection, dialysis is purified; Then make products therefrom with containing 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 purification obtains product b '.
Described step (c) is specifically according to carrying out as follows: get the obtained product of step (b) and Compound C is dissolved in methanol solvate, 24-48h is reacted under room temperature, after reaction terminates, by rotary evaporation except desolventizing, then the unreacted Compound C of dialysis removing in methyl alcohol, obtains the noble metal nano particles of finishing azido group.Described Compound C preferred 1-alkyl azide amine, wherein the carbon atom number of alkyl is at 3 ~ 5, such as the homologue such as 1-nitrine propylamine, 1-nitrine butylamine.
In described step (c), the product that step (b) is obtained 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 the obtained noble metal nano particles having modified azido group of step (c) and be dissolved in N with the smaller ligand containing alkynyl, in dinethylformamide, add copper sulphate/sodium ascorbate and 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 smaller ligand containing alkynyl is N, N-(4-alkynyl)-diethylenetriamines-tetraacethyl, and its structure is as follows:
In described step (d), the noble metal nano particles having modified azido group is that 1:1-2 feeds intake with the smaller ligand containing alkynyl according to the mol ratio of azido and alkynyl, and the molar ratio containing the smaller 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), the muriatic reaction of product d and paramagnetic metal is carried out in the mixed solvent of dimethyl sulfoxide (DMSO) and water, and product d and paramagnetic metal are that 1:2 ~ 4 feed intake according to the mol ratio of smaller ligand and paramagnetic metal.
Noble metal/paramagnetic metal the 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.
Accompanying drawing explanation
Fig. 1 is the infrared spectrogram of the gold/gadolinium composite nanoparticle of the individual layer nucleocapsid structure that embodiment 1 obtains.
Fig. 2 is the transmission electron microscope picture of the gold/gadolinium composite nanoparticle of the individual layer nucleocapsid structure that embodiment 1 obtains.
Fig. 3 is the planar structure schematic diagram of the gold/gadolinium composite nanoparticle of two-layer nucleocapsid structure.
Fig. 4 is gold/gadolinium nano particle (1) and commercial Magnevist Solution (2) nuclear magnetic resonance in pure water (MRI) image of different gadolinium ion concentration, and sample concentration is followed successively by from top to bottom: 1.00,0.50,0.25,0.125,0.0625,0.0mmolL
-1.
Fig. 5 is the gold/computed tomography of gadolinium nano-particle compound in pure water (CT) image of variable concentrations, sample concentration is followed successively by 1.00 from left to right, 0.50,0.25,0.125,0.0625,0.0mmolL
-1.
Detailed description of the invention
Following instance is provided in order to set forth spy of the present invention further.Obvious embodiments of the present invention are not limited to following embodiment.
The smaller ligand that the embodiment of the present invention uses is N, N-(4-alkynyl)-diethylenetriamines-tetraacethyl.
Embodiment 1
Step a: under stirring at 25 DEG C, adding 3mL concentration in 100mL deionized water is 0.03molL
-1sodium citrate solution, heat while stirring to boiling.After solution boiling, add rapidly 1mL concentration is 0.02molL
-1chlorogold solution and heat and micro-ly boil stirring after 5 minutes, stop stirring and heating, be cooled to room temperature, obtain the golden nanometer particle hydrosol that domain size distribution is 5-50nm;
Step b: the golden nanometer particle hydrosol 10mL methyl alcohol getting 2mL step a obtained disperses again, 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 is dialysed in methyl alcohol, revolve steam the most of methanol solvate of removing after with 20mL methyl acrylate room temperature under react 48 hours, the dialysis membrane that reactant mixture is 3500Da through molecular cut off is dialysed in methyl alcohol, concentrated by rotary evaporation, freeze-drying obtain product b;
Product b detects through Fourier infrared spectrograph and shows golden nanometer particle finishing compounds containing thiol groups, sees Fig. 1; Transmission electron microscope shows that the particle diameter of product b is about 80nm, sees Fig. 2.
Step c: product b is put in 10mL methyl alcohol, then 30mL1-nitrine propylamine is added, under room temperature react 12 hours, the dialysis membrane that mixture is 3500Da through molecular cut off is dialysed in methyl alcohol, concentrated by rotary evaporation, freeze-drying, obtain the single layer of gold nano particle of finishing azido group;
Steps d: get the single layer of gold nano-complex particle having modified azido group that 0.1g step c obtains and 2g and be dissolved in 5mLN containing the smaller 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, reactant mixture chloroform/water (volume ratio 1:1) extract and separate, collect organic solvent portion, and carry out Ultrafiltration Purifying, freeze-drying obtains product d;
Step e: product d reacts 2 hours, freeze-drying after reactant mixture Ultrafiltration Purifying with 5g gadolinium chloride again in 15mL dimethyl sulfoxide (DMSO)/water (volume ratio 1:2) mixed solution, obtains the gold/gadolinium composite nanoparticle of individual layer nucleocapsid structure.
Embodiment 2 (with embodiment 1, replacing golden nanometer particle with Nano silver grain)
Step a: with vigorous stirring in cryosel bath 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 controlled within 30 minutes.Adding with silver nitrate, reducing agent water liquid color becomes light yellow from colourless gradually, and finally become brown color, namely obtain the Nano silver grain hydrosol, domain size distribution is at 5 ~ 50nm.
Step b: the Nano silver grain hydrosol getting 2mL step a gained; again after disperseing with 50mL methyl alcohol; add 5g2-sulfydryl-5-aminobenzimidazole; under the protection of nitrogen; stir lucifuge in 20 DEG C of constant temperature and react 48 hours; the dialysis membrane that reactant mixture is 3500Da through molecular cut off is dialysed in methyl alcohol, concentrated by rotary evaporation, put in 10mL methanol solution after freeze-drying, then with under 20mL methyl acrylate room temperature reacts 48 hours, reactant mixture dialysis purifying.
Step c: the product after step b purifying is dissolved in 10ml methyl alcohol, then add 30mL1-nitrine propylamine, react 12 hours under room temperature, freeze-drying after mixture dialysis purifying, obtains the single-layer silver nanoparticle of finishing azido group.
Steps d: get the single-layer silver nanoparticle compound having modified azido group that 0.1g step c obtains and 2g and be dissolved in 5mLN containing the smaller ligand of alkynyl, in dinethylformamide, under each 0.1mol of copper sulphate/sodium ascorbate exists, room temperature reaction 12 hours, the each 5mL extract and separate of reactant mixture chloroform/water, collect organic solvent portion, and carry out Ultrafiltration Purifying, freeze-drying obtains product d.
React 2 hours, freeze-drying after reactant mixture Ultrafiltration Purifying in step e: the product d mixed solvent formed at 5mL dimethyl sulfoxide (DMSO)/10mL water with 10g gadolinium chloride again, obtain the silver/gadolinium composite nanoparticle of individual layer nucleocapsid structure.
Embodiment 3
Step a, under stirring at 25 DEG C, in 100mL deionized water, add 3mL concentration is 0.03molL
-1sodium citrate solution, heat while stirring to boiling.After solution boiling, add rapidly 1mL concentration is 0.02molL
-1chlorogold solution and heat and micro-ly boil stirring after 5 minutes, stop stirring and heating is cooled to room temperature, obtain the golden nanometer particle hydrosol that domain size distribution is 5-50nm.
Step b, the golden nanometer particle hydrosol 10mL methyl alcohol getting 2mL step a obtained 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 steaming the most of methanol solvate of removing with under 20mL methyl acrylate room temperature and react 48 hours, in 10mL methanol solvate, 24 hours are reacted again with under 5g3-sulfydryl-PABA room temperature after reactant mixture dialysis purifying, 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 to be continued with 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 and 10g1-nitrine butylamine react 24 hours in 20mL methyl alcohol under room temperature, and freeze-drying after reactant mixture dialysis purifying, obtains product c, i.e. the finishing two-layer golden nanometer particle of azido group.
Steps d: get 0.1g product c and 4g and be dissolved in 15mLN containing the smaller ligand of alkynyl, in dinethylformamide, under each 0.1mol of copper sulphate/sodium ascorbate exists, room temperature reaction 12 hours, reactant mixture 10mL chloroform, 10mL water mixed solution extract and separate, collect organic solvent portion, after rotary evaporation removing organic solvent, obtain product d.
React 4 hours, freeze-drying after reactant mixture Ultrafiltration Purifying under room temperature in the mixed solvent that step e, product d form at 10mL dimethyl sulfoxide (DMSO), 20mL water with 10g gadolinium chloride again, obtain the gold/gadolinium composite nanoparticle of two-layer nucleocapsid structure.
Embodiment 4 (with embodiment 3, replacing golden nanometer particle with Nano silver grain)
Step a: with vigorous stirring in cryosel bath 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 controlled within 30 minutes.Adding with silver nitrate, reducing agent water liquid color becomes light yellow from colourless gradually, and finally become brown color, namely obtain the Nano silver grain hydrosol, its domain size distribution is at 5 ~ 50nm.
Step b: the Nano silver grain hydrosol getting 2mL step a gained, again after disperseing with 50mL methyl alcohol, add 5g3-sulfydryl-PABA, under the protection of nitrogen, stir lucifuge in 20 DEG C of constant temperature and react 48 hours, the dialysis membrane that reactant mixture is 3500Da through molecular cut off is dialysed in methyl alcohol, revolve and steam except desolventizing, put in 10mL methanol solution after freeze-drying, then 20mL ethyl acrylate is added, react 24 hours under room temperature, in 10mL methanol solvate, 24 hours are reacted again with under 5g3-sulfydryl-PABA room temperature after reactant mixture dialysis purifying, after dialysis again with the 5mL Nano silver grain hydrosol in 20mL pure water room temperature reaction 24 hours under nitrogen protection, obtain two-layer divergent shape Nano silver grain compound.Continued in 20mL methyl alcohol, to react 24 hours with 10g2-sulfydryl-5-aminobenzimidazole under room temperature, react 24 hours again after dialysis purifying with 20mL methyl acrylate in 20mL methyl alcohol under room temperature, after dialysis purifying, freeze-drying obtains product b.
Step c, product b and 10g1-nitrine butylamine react 12 hours in 30mL methyl alcohol under room temperature, and freeze-drying after reactant mixture dialysis purifying, obtains product c, i.e. the finishing two-layer Nano silver grain of azido group.
Steps d: get the two-layer Nano silver grain compound having modified azido group that 0.1g step c obtains and 5g and be dissolved in 20mLN containing the smaller ligand of alkynyl, in dinethylformamide, room temperature reaction 12 hours under each 0.1mol of copper sulphate/sodium ascorbate exists, the each 5ml extract and separate of reactant mixture chloroform/water, collect organic solvent portion, after rotary evaporation removing organic solvent, obtain product d.
Step e, product d reacts 2 hour under room temperature with 10g gadolinium chloride again in 10ml water mixed solution, freeze-drying after reactant mixture Ultrafiltration Purifying, obtains the silver/gadolinium composite nanoparticle of two-layer nucleocapsid structure.
Embodiment 5
The end product that embodiment 1 obtains is 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, test imaging effect respectively 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 of molecular imaging, early diagnosis of tumor, gene imaging expression, drug disposition transmission.
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 made, change, accommodation or alternative, all within protection scope of the present invention.
Claims (9)
1. have noble metal/paramagnetic metal composite nanoparticle of nucleocapsid structure, its preparation method comprises the following steps:
A () prepares the noble metal nano particles that particle diameter is 5-50nm; Described noble metal is gold or silver-colored;
B () gets containing sulfydryl and amino compd A, the sulfydryl in noble metal nano particles prepared by step (a) and compd A reacts and forms M-S-key, and M is Au or Ag, obtains product a; Make the amino in product a and methyl acrylate react again to be formed
obtain product b;
C () gets containing azido group and amino Compound C, make to contain in the product of step (b)
in ester group and amino in Compound C react and formed
key, obtains the noble metal nano particles of finishing azido group;
D () is got the obtained noble metal nano particles having modified azido group of step (c) and is carried out Click reaction with the smaller ligand containing alkynyl, obtain product d;
E () makes the chloride of product d and paramagnetic metal react, obtain having the noble metal/paramagnetic metal composite nanoparticle of nucleocapsid structure after reaction terminates through separation and purification.
2. there is the noble metal/paramagnetic metal composite nanoparticle of nucleocapsid structure as claimed in claim 1, it is characterized in that described step b also comprises step b': get containing sulfydryl and amino compd A ', make to contain in product b
in ester group and compd A ' in amino react and formed
key, the noble metal nano particles making the sulfydryl that contains in products therefrom obtained with step (a) again reacts and generates-S-M key, then get containing sulfydryl and amino compd A "; products therefrom is continued and compd A " in the sulfydryl that contains react formation-S-M-S-, then the amino that contains in products therefrom and methyl acrylate are reacted formed
obtain product b '.
3. there is the noble metal/paramagnetic metal composite nanoparticle of nucleocapsid structure as claimed in claim 2, it is characterized in that: using the product of step b ' as raw material, repeatedly repeat the operation of step b ', to form the product with multilayer noble metal nano particles.
4. the noble metal with the nucleocapsid structure/paramagnetic metal composite nanoparticle as described in one of claims 1 to 3, is characterized in that: described compd A is selected from one of following: 2-sulfydryl-5-aminobenzimidazole, 3-sulfydryl-PABA, mercaptoethylmaine.
5. there is the noble metal/paramagnetic metal composite nanoparticle of nucleocapsid structure as claimed in claim 2 or claim 3, it 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. the noble metal with the nucleocapsid structure/paramagnetic metal composite nanoparticle as described in one of claims 1 to 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. the noble metal with the nucleocapsid structure/paramagnetic metal composite nanoparticle as described in one of claims 1 to 3, it is characterized in that the described smaller ligand containing alkynyl is N, N-(4-alkynyl)-diethylenetriamines-tetraacethyl, its structure is as follows:
8. noble metal/paramagnetic metal the composite nanoparticle as claimed in claim 1 with nucleocapsid structure strengthens the application of contrast medium as MRI.
9. noble metal/paramagnetic metal the composite nanoparticle as claimed in claim 1 with nucleocapsid structure strengthens the application of contrast medium as CT.
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| CN102258793A (en) * | 2011-07-14 | 2011-11-30 | 长春理工大学 | Application of core-shell nano particle |
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