CN108311709A - A kind of gold nano thorn and its preparation method and application - Google Patents
A kind of gold nano thorn and its preparation method and application Download PDFInfo
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- 229910052737 gold Inorganic materials 0.000 title claims abstract description 126
- 239000010931 gold Substances 0.000 title claims abstract description 126
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 title claims abstract description 106
- 238000002360 preparation method Methods 0.000 title claims abstract description 33
- 229920000642 polymer Polymers 0.000 claims abstract description 78
- 239000002245 particle Substances 0.000 claims abstract description 54
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 31
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 31
- 238000006722 reduction reaction Methods 0.000 claims abstract description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000012279 sodium borohydride Substances 0.000 claims abstract description 22
- 229910000033 sodium borohydride Inorganic materials 0.000 claims abstract description 22
- 238000001338 self-assembly Methods 0.000 claims abstract description 21
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims abstract description 20
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 18
- 239000002872 contrast media Substances 0.000 claims abstract description 10
- 229910001961 silver nitrate Inorganic materials 0.000 claims abstract description 10
- 229960005070 ascorbic acid Drugs 0.000 claims abstract description 9
- 235000010323 ascorbic acid Nutrition 0.000 claims abstract description 9
- 239000011668 ascorbic acid Substances 0.000 claims abstract description 9
- 238000002156 mixing Methods 0.000 claims abstract description 7
- 239000000243 solution Substances 0.000 claims description 81
- 150000001875 compounds Chemical class 0.000 claims description 43
- XSLZWOACNCSOBR-UHFFFAOYSA-N [Au].Cl(=O)(=O)(=O)O Chemical compound [Au].Cl(=O)(=O)(=O)O XSLZWOACNCSOBR-UHFFFAOYSA-N 0.000 claims description 21
- 238000006068 polycondensation reaction Methods 0.000 claims description 19
- 239000000126 substance Substances 0.000 claims description 19
- 238000003384 imaging method Methods 0.000 claims description 15
- 238000005886 esterification reaction Methods 0.000 claims description 10
- 238000005859 coupling reaction Methods 0.000 claims description 9
- 230000032050 esterification Effects 0.000 claims description 9
- 241000549556 Nanos Species 0.000 claims description 6
- 230000008859 change Effects 0.000 claims description 5
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims description 3
- KJJPLEZQSCZCKE-UHFFFAOYSA-N 2-aminopropane-1,3-diol Chemical compound OCC(N)CO KJJPLEZQSCZCKE-UHFFFAOYSA-N 0.000 claims description 3
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- 229910052796 boron Inorganic materials 0.000 claims description 3
- 235000013339 cereals Nutrition 0.000 claims description 3
- 239000002504 physiological saline solution Substances 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 229940014800 succinic anhydride Drugs 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 2
- 240000007594 Oryza sativa Species 0.000 claims 1
- 235000007164 Oryza sativa Nutrition 0.000 claims 1
- 150000004703 alkoxides Chemical class 0.000 claims 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims 1
- 238000006116 polymerization reaction Methods 0.000 claims 1
- 235000009566 rice Nutrition 0.000 claims 1
- 235000002639 sodium chloride Nutrition 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- 229960002668 sodium chloride Drugs 0.000 claims 1
- -1 CTBA Substances 0.000 abstract description 11
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 abstract description 6
- 229920002125 Sokalan® Polymers 0.000 abstract description 3
- 235000019136 lipoic acid Nutrition 0.000 abstract description 2
- 239000004584 polyacrylic acid Substances 0.000 abstract description 2
- 229960002663 thioctic acid Drugs 0.000 abstract description 2
- AGBQKNBQESQNJD-UHFFFAOYSA-M lipoate Chemical compound [O-]C(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-M 0.000 abstract 1
- 229920000151 polyglycol Polymers 0.000 abstract 1
- 239000010695 polyglycol Substances 0.000 abstract 1
- 238000000034 method Methods 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 238000000502 dialysis Methods 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 239000002105 nanoparticle Substances 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- 238000001035 drying Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 238000011097 chromatography purification Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000000862 absorption spectrum Methods 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical compound OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000002086 nanomaterial Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 0 CCC(*)CNC(CCCCCC1SSCC1)=N Chemical compound CCC(*)CNC(CCCCCC1SSCC1)=N 0.000 description 2
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 229960003067 cystine Drugs 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000002070 nanowire Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000002601 radiography Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000012498 ultrapure water Substances 0.000 description 2
- 241000208140 Acer Species 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- QBQSGKIFRYENSH-VUWPPUDQSA-O C[C@@H](CCNC)NC(CCCC(CC[SH2+])S)=O Chemical compound C[C@@H](CCNC)NC(CCCC(CC[SH2+])S)=O QBQSGKIFRYENSH-VUWPPUDQSA-O 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 244000283207 Indigofera tinctoria Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002091 nanocage Substances 0.000 description 1
- 239000002078 nanoshell Substances 0.000 description 1
- 239000002077 nanosphere Substances 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000005287 template synthesis Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B22—CASTING; POWDER METALLURGY
- B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
- B22F9/00—Making metallic powder or suspensions thereof
- B22F9/16—Making metallic powder or suspensions thereof using chemical processes
- B22F9/18—Making metallic powder or suspensions thereof using chemical processes with reduction of metal compounds
- B22F9/24—Making metallic powder or suspensions thereof using chemical processes with reduction of metal compounds starting from liquid metal compounds, e.g. solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
- A61K49/225—Microparticles, microcapsules
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B22—CASTING; POWDER METALLURGY
- B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
- B22F1/00—Metallic powder; Treatment of metallic powder, e.g. to facilitate working or to improve properties
- B22F1/07—Metallic powder characterised by particles having a nanoscale microstructure
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y30/00—Apparatus for additive manufacturing; Details thereof or accessories therefor
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y40/00—Auxiliary operations or equipment, e.g. for material handling
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- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Acoustics & Sound (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Crystallography & Structural Chemistry (AREA)
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- Animal Behavior & Ethology (AREA)
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Abstract
The present invention provides a kind of gold nano thorns and its preparation method and application, belong to acousto-optic image-forming contrast medium technical field, including following preparation process：Perchloric acid gold, CTBA, sodium borohydride are mixed with water, reduction reaction occurs, obtains CTBA gold nano kind solution；Perchloric acid gold, polymer template molecule and water are mixed, complex solution is obtained；CTBA gold nano kind solution and the water mixing that obtained complex solution, silver nitrate, the step 1) are obtained carry out self assembly, obtain the solution after self assembly；Solution after obtained self assembly is mixed with ascorbic acid and carries out reduction reaction, obtains gold nano thorn；The polymer template molecule is that multiple tooth sulfydryl replaces lipoic acid polyethylene glycol or combed polyacrylic acid mercapto-polyglycol polymer.The present invention obtains the single gold nano of pattern by polymer template molecule and CTBA plate sharings and pierces particle.
Description
Technical field
The present invention relates to acousto-optic image-forming contrast medium technical field more particularly to a kind of gold nano thorn and preparation method thereof and answer
With.
Background technology
Gold nanoparticle is to study a kind of nano material earlier, is being catalyzed at present, photoelectron, the necks such as biomedicine
Domain is widely used, and the property of gold nanoparticle is often related to its size and pattern, by developing different synthesis sides
Method has obtained nanosphere, nanocube, nanometer tetrahedron, hexahedron, nanometer plate, pyramid nano-particle, nanometer rods,
Nano wire, nanocages, nanoshell, nanometer magnitude various structures.The property of gold nanoparticle is also by the molecule knot of its adsorption
The influence of structure, such as surface Raman effect just have relationship with the size of gold nanoparticle, shape and surface molecular.
The synthetic method for the gold nano thorn reported at present is seldom, and gold nano star is that one kind of similar gold nano thorn is complex
Structure, usually complicated gold nano structure be all by Template synthesis, cetyl trimethylammonium bromide, abbreviation CTBA,
It is more common template, is commonly used to synthesis nanometer rods, nano wire and various other nano shape gold particles, is used alone
CTBA is that the gold nanoparticle pattern of templated synthesis is not usually single, can be mixed with the nano-particle of other structures, such as synthesis gold
Other spherical or cubic structure particles can be mixed when nanometer rods.Such case also has body in synthesis gold nano magnitude labyrinth
It is existing, not single pattern, fault of construction or missing are shown as, uniform nanostructure is obtained by the reaction it is difficult to control.
Invention content
In view of this, the purpose of the present invention is to provide a kind of gold nano thorn and its preparation method and application, the present invention is logical
It crosses and uses gold nano thorn pattern made from method of the polymer template molecule with CTBA co-templates single, particle is uniform.
In order to achieve the above-mentioned object of the invention, the present invention provides following technical scheme：
A kind of preparation method of gold nano thorn, including following preparation process：
1) perchloric acid gold, CTBA, sodium borohydride are mixed with water and reduction reaction occurs, it is molten to obtain CTBA- gold nano kinds
Liquid；
2) perchloric acid gold, polymer template molecule and water are mixed, obtains complex solution；
3) the CTBA- gold nano kinds for obtaining complex solution, silver nitrate, the step 1) that the step 2) obtains
Solution and water mixing carry out self assembly, obtain the solution after self assembly；
4) solution after self assembly that the step 3) obtains is mixed with ascorbic acid and carries out reduction reaction, obtain Jenner
Rice thorn；
The step 1) and step 2) do not have sequencing；
Polymer template molecule is that multiple tooth sulfydryl replaces lipoic acid-polyethylene glycol or combed polypropylene in the step 1)
Acid-sulfydryl-polyethylene glycol polymer；
The multiple tooth sulfydryl alternating lipoic acid-polyethylene glycol has structure shown in Formulas I：
The integer that the n is 40~50；
Combed polyacrylic acid-sulfydryl-the polyethylene glycol polymer has structure shown in Formula II：
The integer that the n is 40~50.
Preferably, the ratio between the amount of substance of perchloric acid gold, CTBA and sodium borohydride are 1 in the step 1)：200~
400：2~3.
Preferably, the concentration of CTBA- gold nanos kind solution is calculated as 0.08~0.1mol/L with CTBA in the step 1).
Preferably, the ratio between perchloric acid gold and the amount of substance of polymer template molecule are 30~40 in the step 2)：1.
Preferably, the concentration of complex solution is calculated as 7~10mg/mL with polymer template molecule in the step 2).
Preferably, the polymer template molecule in the step 3) in complex solution, silver nitrate, CTBA- gold nano kinds
The ratio between amount of substance of middle CTBA is 1：3：14~70.
Preferably, in the step 4) ascorbic acid with the complex solution perchloric acid for preparing the self assembly solution
The ratio between amount of substance of gold is 1：1~2：1.
Preferably, the preparation method of the multiple tooth sulfydryl alternating lipoic acid-polyethylene glycol includes the following steps：
1) compound with structure shown in formula III is subjected to coupling reaction with 2- amino -1,3 propylene glycol, is had
The compound of structure shown in formula IV；
2) compound with formula IV structure is subjected to esterification with succinic acid, obtains the change with structure shown in Formula V
Close object；
3) compound with structure shown in Formula V is subjected to polycondensation reaction with the polymer with structure shown in Formula IV, obtained
To the polymer with structure shown in Formula VII；
The integer that n is 40~50 in the Formula IV；
4) there will be Formula VII compound represented to carry out reduction reaction with sodium borohydride, obtain with more shown in Formulas I
Tooth sulfydryl replaces lipoic acid-polyethylene glycol.
Preferably, the preparation method of the multiple tooth sulfydryl alternating lipoic acid-polyethylene glycol includes the following steps：
1) by the polymer with structure shown in Formula VIII and the compound with Formula IX structure and with shown in Formula XI
Compound carries out polycondensation reaction, obtains the polymer with structure shown in Formula X；
The integer that m is 20~30 in shown Formula VIII.
2) polymer with structure shown in Formula X is subjected to reduction reaction with sodium borohydride, obtained with shown in Formula II
Structure combed polyacrylic acid-sulfydryl-polyethylene glycol polymer.
The present invention also provides the gold nano thorn that preparation method described in above-mentioned technical proposal is prepared, the gold nano thorn
Pattern be spherical thorn-like, the grain size of the nearly nanometer thorn is 50nm~200nm.
The present invention also provides the gold nanos to pierce the application in photoacoustic imaging contrast agent.
The present invention provides a kind of gold nano thorns and its preparation method and application, by the present invention in that with polymer template point
Gold nano thorn pattern made from method of the son with CTBA- co-templates is single, and particle is uniform
The present invention can obtain having difference by adjusting the molecular structure and CTBA concentration of the polymer template used
The gold nano of size is pierced, and so as to adjust its optical property, absorption spectrum maximum value is from 550 nanometers to 1100 nanometer；Adjust CTBA
The amount of substance in the reaction is from 4.5 × 10~3Mmol to 22.5 × 10~3What mmol can be obtained from 50 nanometers to 250 nanometer
Gold nano pierces particle.
Adjust the size and optics of the gold nano thorn that concentration of the gold nano kind in reaction solution can be adjusted obviously
Property.
Description of the drawings
The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.
Fig. 1 is that the gold nano obtained in embodiment 1 pierces the electron-microscope scanning figure of particle；
Fig. 2 is that the gold nano obtained in embodiment 2 pierces the electron-microscope scanning figure of particle；
Fig. 3 is that the gold nano obtained in embodiment 3 pierces the electron-microscope scanning figure of particle；
Fig. 4 is that the gold nano obtained in embodiment 4 pierces the electron-microscope scanning figure of particle；
Fig. 5 is that the gold nano obtained in embodiment 5 pierces the electron-microscope scanning figure of particle；
Fig. 6 is that the gold nano obtained in Examples 1 to 6 pierces the absorption spectrum of particle；
Fig. 7 is the photoacoustic imaging figure that gold nano side and gold nano pierce as contrast agent at mouse tumor position in embodiment 1；
Upper figure is the contrasting effects of gold nanorods, and figure below is the contrasting effects of gold nano thorn；
Figure left-to-right is respectively to inject the imaging before gold nano is pierced, 15 minutes after injection nanometer thorn, 1 hour, and 3 hours, 20
The image of hour and 48 hours.
Fig. 8 is that the gold nano obtained in embodiment 6 pierces the electron-microscope scanning figure of particle；
Fig. 9 is that the gold nano obtained in embodiment 7 pierces the electron-microscope scanning figure of particle；
Figure 10 is that the gold nano obtained in embodiment 8 pierces the electron-microscope scanning figure of particle；
Figure 11 is that the gold nano obtained in embodiment 9 pierces the electron-microscope scanning figure of particle；
Figure 12 is that the gold nano obtained in embodiment 10 pierces the electron-microscope scanning figure of particle；
Figure 13 is that the gold nano obtained in embodiment 6~10 pierces the absorption spectrum of particle；
Figure 14 is the photoacoustic imaging that gold nano side and gold nano pierce as contrast agent at mouse tumor position in embodiment 6
Figure；
Upper figure is the contrasting effects of gold nanorods, and figure below is the contrasting effects of gold nano thorn；
Figure left-to-right is respectively to inject the imaging before gold nano is pierced, 15 minutes after injection nanometer thorn, 1 hour, and 3 hours, 20
The image of hour and 48 hours.
Specific implementation mode
The present invention provides a kind of preparation methods of gold nano thorn, including following preparation process：
1) perchloric acid gold, CTBA, sodium borohydride are mixed with water and reduction reaction occurs, it is molten to obtain CTBA- gold nano kinds
Liquid；
2) perchloric acid gold, polymer template molecule and water are mixed, obtains complex solution；
3) the CTBA- gold nano kinds for obtaining complex solution, silver nitrate, the step 1) that the step 2) obtains
Solution and water mixing carry out self assembly, obtain the solution after self assembly；
4) solution after self assembly that the step 3) obtains is mixed with ascorbic acid and carries out reduction reaction, obtain Jenner
Rice thorn；
The step 1) and step 2) do not have sequencing；
Polymer template molecule is that multiple tooth sulfydryl replaces lipoic acid-polyethylene glycol or combed polypropylene in the step 1)
Acid-sulfydryl-polyethylene glycol polymer；
The multiple tooth sulfydryl alternating lipoic acid-polyethylene glycol has structure shown in Formulas I：
The integer that the n is 40~50；
Combed polyacrylic acid-sulfydryl-the polyethylene glycol polymer has structure shown in Formula II：
The integer that the n is 40~50.
The present invention, which mixes perchloric acid gold, CTBA, sodium borohydride with water, occurs reduction reaction, obtains CTBA- gold nano kinds
Solution.In the present invention, the ratio between amount of substance of the perchloric acid gold, CTBA and sodium borohydride preferably 1：200~400：2~
3, more preferably 1：300：2.4.
In the present invention, the concentration of the CTBA- gold nanos kind solution is preferably 0.08~0.1mol/L in terms of CTBA,
More preferably 0.09mol/L.
The present invention obtains CTBA- gold ion complex aqueous solutions after preferably mixing perchloric acid gold, CTBA and water, then again
It is stirred after CTBA- gold ion complex aqueous solutions are mixed with sodium borohydride aqueous solution, reduction reaction occurs, stands at room temperature
To CTBA- gold nano kind solution.
In the present invention, the temperature of the sodium borohydride aqueous solution is preferably 0~4 DEG C, more preferably 0 DEG C.
In the present invention, the rate of the stirring is preferably 300~600 revs/min, more preferably 400 revs/min；It is described to stir
The time mixed is preferably 2~3 minutes, more preferably 2min.
In the present invention, the time of the standing is preferably 20~30 minutes, more preferably 30 minutes.
The present invention mixes perchloric acid gold, polymer template molecule and water, obtains complex solution.In the present invention, institute
State the ratio between perchloric acid gold and the amount of substance of polymer template molecule preferably 30~40：1, more preferably 30：1.In the present invention
In, the gold ion in the perchloric acid gold forms complex with polymer template molecule.
In the present invention, the concentration of the complex solution is preferably 7~10mg/mL in terms of polymer template molecule, more
Preferably 7.8mg/mL.
The present invention is not particularly limited the method for perchloric acid gold, polymer template molecule and water mixing, selects this field
Mixed method known to technical staff.
In the present invention, the preparation method of the multiple tooth sulfydryl alternating lipoic acid-polyethylene glycol preferably includes following steps：
1) compound with structure shown in formula III is subjected to coupling reaction with 2- amino -1,3 propylene glycol, is had
The compound of structure shown in formula IV；
2) compound with formula IV structure is subjected to esterification with succinic acid, obtains the change with structure shown in Formula V
Close object；
3) compound with structure shown in Formula V is subjected to polycondensation reaction with the polymer with structure shown in Formula IV, obtained
To the polymer with structure shown in Formula VII；
The integer that n is 40~50 in the Formula IV；
4) there will be polymer shown in Formula VII to carry out reduction reaction with sodium borohydride, obtain with more shown in Formulas I
Tooth sulfydryl replaces lipoic acid-polyethylene glycol.
Compound with structure shown in formula III is carried out coupling reaction by the present invention with 2~amino~1,3 propylene glycol, is obtained
To the compound with structure shown in formula IV.
In the present invention, the temperature of the coupling reaction is preferably 2~6 DEG C, more preferably 4 DEG C；The coupling reaction
Time is preferably 10~16h, more preferably 12h.
In the present invention, the compound with structure shown in formula III and the substance of 2~amino~1,3 propylene glycol
The ratio between amount preferably 1：1~1：1.5, more preferably 1：1.2.
In the present invention, the solvent of the coupling reaction is preferably the aqueous solution or DMF of DMF, and more preferably DMF's is water-soluble
Liquid；The concentration of the DMF aqueous solutions is preferably 40~60%, and more preferably 50%.
In the present invention, the reducing agent of the reduction reaction is preferably sodium borohydride.
In the present invention, after the completion of the coupling reaction, after coupling reaction product is preferably filtered by the present invention successively
Filtrate, extraction, drying, Chromatographic purification is taken to obtain the compound with structure shown in formula IV.
In the present invention, the extract liquor of the extraction is preferably chloroform.
The present invention is not particularly limited the method for filtering, extraction, drying and Chromatographic purification, selects those skilled in the art
Well known method；In the present invention the column chromatography using silica gel be carrier, using the dichloromethane containing 10% methanol as
Mobile phase.
After obtaining the compound with structure shown in formula IV, the present invention is by compound and fourth two with structure shown in formula IV
Acid carries out esterification, obtains the compound with structure shown in Formula V.
In the present invention, the temperature of the esterification is preferably 40~50 DEG C, the time preferably 2.5 of the esterification
~3.5 days, more preferably 3 days.
In the present invention, the solvent of the esterification is preferably anhydrous chloroform or pyridine, more preferably pyridine.
In the present invention, the compound with structure shown in formula IV and the substance of succinic anhydride progress esterification
The ratio between amount preferably 1：2~1：3, more preferably 1：2.2.
In the present invention, after the completion of the esterification, the present invention preferably esterification reaction product is removed in vacuum successively molten
Agent, washing, drying, Chromatographic purification are obtained with the compound with structure shown in Formula V.
In the present invention, the washing, which will preferably be removed in vacuo the product after solvent and be dissolved in chloroform, washes.This
Invention is not particularly limited the number of washing, selects washing times well known to those skilled in the art.
The present invention is not particularly limited the method for the drying, Chromatographic purification, selects well known to those skilled in the art
Dry, Chromatographic purification method.
It obtains with after the compound with structure shown in Formula V, the present invention is by compound and tool with structure shown in Formula V
There is the polymer of structure shown in Formula IV to carry out polycondensation reaction, obtains the polymer with structure shown in Formula VII.
In the present invention, the solvent of the polycondensation reaction is preferably chloroform or dichloromethane, more preferably chloroform.
In the present invention, the object of the compound with structure shown in Formula V and the polymer with structure shown in Formula IV
The ratio between amount of matter is preferably 1：1.01~1：1.05, more preferably 1：1.05.
In the present invention, the temperature of the polycondensation reaction is preferably 20~30 DEG C, more preferably 25 DEG C, the polycondensation reaction
Time be preferably 12~24 hours, more preferably 16 hours.
In the present invention, the activated carboxylic reactant of the polycondensation reaction is preferably carbonyl dimidazoles (CDI).
In the present invention, after the polycondensation reaction, present invention preferably comprises wash polycondensation product successively, do
Dry, volume removing chromatogram obtains the polymer with structure shown in Formula VII after purification.
The method that the present invention purifies washing, drying and volume removing chromatogram is not particularly limited, and selects art technology
Method known to personnel.
After obtaining the polymer with structure shown in Formula VII, the present invention described will have polymer and boron shown in Formula VII
Sodium hydride carries out reduction reaction, obtains replacing lipoic acid-polyethylene glycol with multiple tooth sulfydryl shown in Formulas I.
In the present invention, the solvent also reacted is preferably ethyl alcohol or water, more preferably ethyl alcohol.
In the present invention, the temperature of the reduction reaction is preferably 4 DEG C or room temperature, more preferably 4 DEG C.
In the present invention, the amount of the substance of the cystine linkage and sodium borohydride in polymer shown in Formula VII it
Than being 1：2.
The present invention is not particularly limited the time of reduction reaction, and reaction solution restores anti-after becoming purple or blue from white
It should terminate.
In the present invention, after the completion of reduction reaction, reduction reaction product is preferably subjected to dialysis separating-purifying, is had
Multiple tooth sulfydryl shown in Formulas I replaces lipoic acid-polyethylene glycol.The present invention is not particularly limited the method for separating-purifying of dialysing,
Select method well known to those skilled in the art；The molecular cut off of the dialysis dialysis membrane is 1000.
In the present invention, the preparation principle of the multiple tooth sulfydryl alternating lipoic acid-polyethylene glycol is shown below：
In the present invention, the preparation method of the combed polyacrylic acid-sulfydryl-polyethylene glycol polymer preferably includes following
Step：
1) by the polymer with structure shown in Formula VIII and the compound with Formula IX structure and with shown in Formula XI
Compound carries out polycondensation reaction, obtains the polymer with structure shown in Formula X；
The integer that m is 20~30 in the Formula VIII；
2) polymer with structure shown in Formula X is subjected to reduction reaction with sodium borohydride, obtained with shown in Formula II
Structure combed polyacrylic acid-sulfydryl-polyethylene glycol polymer.
The present invention is by the polymer with structure shown in Formula VIII and the compound with Formula IX structure and with Formula XI institute
The compound shown carries out polycondensation reaction, obtains the polymer with structure shown in Formula X.In the present invention, the polycondensation reaction
Solvent is preferably dimethyl sulfoxide or DMF, more preferably dimethyl sulfoxide.
In the present invention, the polymer with structure shown in Formula VIII with Formula IX structure compound and have
The ratio between amount of substance of Formula XI compound represented is preferably 1：12~13：12~13, more preferably 1：12.5：12.5.
The present invention is not particularly limited the source of the polymer with structure shown in Formula VIII, and selection commercial goods are
It can.
In the present invention, the temperature of the polycondensation reaction is preferably room temperature；The time of the polycondensation reaction is selected as 10~
16h, more preferably 12~14h.
After the completion of the polycondensation reaction, polycondensation product is preferably carried out dialysis separating-purifying by the present invention, is had
The polymer of structure shown in Formula X.The present invention is not particularly limited the method for the dialysis separating-purifying, selects art technology
The method of separating-purifying known to personnel；The molecular cut off of the dialysis membrane is preferably 10000.
After obtaining the polymer with structure shown in Formula X, the present invention is to polymer and hydroboration with structure shown in Formula X
Sodium carries out reduction reaction, obtains with structure combed polyacrylic acid-sulfydryl-polyethylene glycol polymer shown in Formula II.
In the present invention, the solvent of the reduction reaction is preferably ethyl alcohol or ethanol water, and more preferably ethyl alcohol is water-soluble
The volume ratio of liquid, the ethanol water ethyl alcohol and water is preferably 1：1.
In the present invention, in the polymer with structure shown in Formula X the substance of cystine linkage and sodium borohydride amount it
Than being preferably 1：2 or 1：3, more preferably 1：2.
In the present invention, the temperature of the reduction reaction is preferably room temperature, and time of the reduction reaction is preferably 3~
5h, more preferably 4h.
In the present invention, after the completion of reduction reaction, preferably include by reduction reaction product carry out dialysis separating-purifying obtain
With structure combed polyacrylic acid-sulfydryl-polyethylene glycol polymer shown in Formula II；The molecular cut off when dialysis is preferred
It is 10000.
In the present invention, the preparation principle of the combed polyacrylic acid-sulfydryl-polyethylene glycol polymer is shown below：
After obtaining complex solution and CTBA- gold nano kind solution, the present invention is by the complex solution, silver nitrate, institute
It states CTBA- gold nano kind solution and water mixing carries out self assembly, obtain the solution after self assembly.
In the present invention, in the polymer template molecule in the complex solution, silver nitrate, CTBA- gold nano kinds
The ratio between amount of substance of CTBA is preferably 1：3：14~70；More preferably 1：3：14 or 1：3：28 or 1：3：42 or 1：3：56 or
1：3：70.
The present invention does not have special limit to the mixed method of complex solution, silver nitrate, CTBA- gold nano kind solution and water
It is fixed, select mixed method well known to those skilled in the art.
After obtaining the solution after self assembly, the solution after obtained self assembly is mixed with ascorbic acid and is gone back by the present invention
Original reaction obtains gold nano thorn.
In the present invention, the complex solution perchloric acid gold of the ascorbic acid and the prepared self assembly solution
The ratio between amount of substance is preferably 1：1~2：1, more preferably 1.6：1：1.
In the present invention, the temperature of the reduction reaction is preferably 20~40 DEG C, more preferable 25 DEG C；The reduction reaction
Time is preferably 20 minutes~1 hour, more preferably 30 minutes.
The present invention also provides the gold nano thorn that the preparation method is prepared, the pattern of the gold nano thorn is spherical shape
The grain size of thorn-like, the gold nano thorn is 50nm~200nm.
The present invention also provides the gold nanos to pierce the application in photoacoustic imaging contrast agent.
Gold nano thorn particle dilutes (0.1 micromoles per liter of solution concentration, 10~50 skin of usage amount rub) in physiological saline,
Using tail vein injection method injection Mice Body in, after mouse anesthesia in different times section to its tumor locus carry out optoacoustic at
As (iThera MSOT in vision128 photoacoustic imaging instrument, Germany), stepping 1mm, 680~900nm of exciting light, mostly light are scanned
Spectrum imaging obtained by 270 ° of arcuate array converters, collection of illustrative plates by instrument carry software analyze, light be gold nano thorn or
Gold nanorods particle photoacoustic signal.
Gold nano provided by the invention is pierced and preparation method thereof with reference to embodiment and is described in detail, but not
They can be interpreted as limiting the scope of the present invention.
Embodiment 1
The synthesis of polymer template molecule
1) exist to 2- amino-2-methyls -1,3 propylene glycol (0.74g, 7.0mmol) and sodium borohydride (0.58g, 6.9mmol)
The mixed solution and dripping of DMF/ water (10mL/10mL) has the lipoic acid-NHS (1.77g, 5.8mmol) of structure shown in formula III
DMF (3mL) solution, reaction solution temperature is maintained at 4 DEG C or so, is stirred overnight at room temperature.Chlorine is used after reaction mixture filtering
Imitative extraction merges washing and drying after organic phase, and by column chromatography, (silica gel is stationary phase to crude product, contains the dichloromethane of 10% methanol
Alkane is mobile phase) separating-purifying obtains the compound with structure shown in formula IV.
The compound (0.35g, 1.2mmol) with structure shown in formula IV that will be obtained, succinic anhydride (0.3 g, 3mmol)
And 4-dimethylaminopyridine (23mg, 0.19mmol) is dissolved in anhydrous pyridine (5mL), reaction mixture is under the conditions of 45 degree
It is stirred to react 3 days.Pyridine is removed in vacuum after reaction, reaction mixture, which is dissolved in chloroform, to be washed three times.After merging organic phase
It is dry, the compound that crude product is obtained having structure shown in Formula V by column chromatography separating-purifying.
Compound (0.2g, 0.5mmol) with Formula V structure is dissolved in the solution in anhydrous chloroform (20mL) and CDI is added
The nothing of the two amido polyethylene glycol (1.02g, 0.5mmol) with Formula IV structure is added in (0.25g, 1.5mmol) after reaction overnight
Water chloroformic solution.Reaction is overnight.Organic phase washing is dried afterwards three times.The yellow that crude product is obtained after purification with volume removing chromatogram
Product is the polymer with structure shown in Formula VII.
Sodium borohydride reduction is added in the in the mixed solvent that polymer with structure shown in Formula VII is dissolved in ethyl alcohol and water,
Product dialysis separating-purifying obtains the compound with structure shown in Formulas I.
2) to polyacrylic acid (PAA) (100mg, 5.5 × 10~2Mmol) in the solution in anhydrous dimethyl Asia maple (3mL)
EDC (392mg, 2.0mmol) and NHS (192mg, 1.7mmol) is added, is stirred to react at room temperature overnight.Amino lipoic acid
(150mg, 0.6mmol), the polyacrylic acid that aminomethoxy polyethylene glycol (0.83g, 0.4mmol) is added to after above-mentioned activation are anti-
It answers in solution, reaction at room temperature is stayed overnight.Obtained crude product is through separating-purifying of dialysing.Purified polymer solution (1.4g,
4.7×10~2Mmol sodium borohydride (37mg, 1.0mmol)) is added to restore, reacts 4 hours at room temperature, dialysis removes unreacted
Sodium borohydride obtain that there is the compound of structure shown in Formula II to obtain the compound with structure shown in Formula II.
The synthesis of gold nano thorn
1) solution (0.25mL) of the perchloric acid gold in high purity water (0.01 mol/L), is added a certain amount of CTBA (0.1
Mol/L, 7.5mL), gold ion forms complex (solution colour becomes khaki) with CTBA- and ice-cold boron hydrogen is added afterwards
Change sodium water solution (0.01 mol/L, 0.6mL), rapid stirring stands under 25 degrees Celsius after 2 minutes and obtains CTBA- gold nanos
Kind solution, obtained nanogold seed solution are immediately used to the templated synthesis of gold nano thorn.
2) polymer in-mold with Formulas I structure is added in the solution (0.01 mol/L, 1 milliliter) of high purity water in perchloric acid gold
Plate molecule (0.15mL, 9mg), solution from yellow to red, then becoming yellow again again, (with gold ion formation match by dihydro thiotic molecules
Close object) obtain complex solution.
3) aqueous solution that 5 minutes are added silver nitrate is stirred at room temperature in the complex solution obtained, and (0.1mL, 0.01 rubs
You/liter), CTBA gold nano kind solution 0.05mL is added in said mixture and stirs ten minutes.The color of reaction solution is by xanthochromia
Orange, and milk shape is become by clear, this illustrates that polymer~gold ion is self-assembly of micron with CTBA- gold nano kinds
The structure of scale.
4) ascorbic acid solution (0.16mL, 0.1mol/L) is added in solution into the solution after above-mentioned self assembly to restore
Tervalence gold ion, reaction solution color bleach, and color change purple or indigo plant after half an hour are stood and (stop stirring) by reaction solution
Color obtains gold nano thorn particle.
Obtained nanogold thorn particle electron-microscope scanning figure is as shown in Figure 1, as shown in Figure 1, the nanogold obtained in embodiment 1
Thorn particle morphology is single, and particle size is uniform, is 30nm or so.
Obtained gold nano pierces photoacoustic imaging such as Fig. 7 figure below (second row) institute as contrast agent at mouse tumor position
Show, upper figure (first row is the radiography figure of gold nanorods), figure left-to-right is respectively the imaging injected before gold nano thorn, injects nanometer
Imaging in 15 minutes, 1 hour, 3 hours, 20 hours and 48 hours after thorn.Gold nano is pierced in tumour as seen from the figure as shown in Figure 7
Position has the retention time being obviously prolonged.
In the abosrption spectrogram such as Fig. 6 of obtained gold nano thorn shown in curve a.
Embodiment 2
CTBA gold nano kind solution is 0.10mL, other identical with embodiment 1.
Obtained nanogold thorn particle electron-microscope scanning figure is as shown in Fig. 2, as shown in Figure 2, the nanogold obtained in embodiment 2
Thorn particle morphology is single, and particle size is uniform, is 50nm.
In the abosrption spectrogram such as Fig. 6 of obtained gold nano thorn shown in curve b.
Embodiment 3
CTBA gold nano kind solution is 0.15mL, other identical with embodiment 1.
Obtained nanogold pierces particle electron-microscope scanning figure as shown in figure 3, from the figure 3, it may be seen that the nanogold obtained in embodiment 3
Thorn particle morphology is single, and particle size is uniform, is 100nm.
In the abosrption spectrogram such as Fig. 6 of obtained gold nano thorn shown in curve c.
Embodiment 4
CTBA gold nano kind solution is 0.20mL, other identical with embodiment 1.
Obtained nanogold thorn particle electron-microscope scanning figure is as shown in figure 4, as shown in Figure 4, the nanogold obtained in embodiment 4
Thorn particle morphology is single, and particle size is uniform, is 150nm.
In the abosrption spectrogram such as Fig. 6 of obtained gold nano thorn shown in curve d.
Embodiment 5
CTBA gold nano kind solution is 0.25mL, other identical with embodiment 1.
Obtained nanogold thorn particle electron-microscope scanning figure is as shown in figure 5, as shown in Figure 5, the nanogold obtained in embodiment 5
Thorn particle morphology is single, and particle size is uniform, is 200nm.
In the abosrption spectrogram such as Fig. 6 of obtained gold nano thorn shown in curve e.
By each curve comparison in Fig. 6 it is found that with CTBA template molecules dosage in reaction solution increase, obtained gold nano
Pierce the gradual red shift of absorption spectrum of particle.
Embodiment 6
Polymer template molecule polymer shown in Formulas I is replaced with into polymer shown in Formula II, remaining CTBA Jenner
Rice kind solution is 0.05mL, other identical with embodiment 1.
Obtained nanogold thorn particle electron-microscope scanning figure is as shown in Figure 8.As shown in Figure 8, the nanogold obtained in embodiment 1
Thorn particle morphology is single, and particle size is uniform, is 25~30 rans.
Obtained gold nano pierces photoacoustic imaging such as Figure 14 figure below (second row) institute as contrast agent at mouse tumor position
Show, upper figure (first row is the radiography figure of gold nanorods), figure left-to-right is respectively the imaging injected before gold nano thorn, injects nanometer
Imaging in 15 minutes, 1 hour, 3 hours, 20 hours and 48 hours after thorn.Gold nano is pierced in tumour as seen from the figure as shown in Figure 7
Position has the retention time being obviously prolonged.
In the abosrption spectrogram such as Figure 13 of obtained gold nano thorn shown in curve a.
Embodiment 7
CTBA gold nano kind solution is 0.1mL, other identical with embodiment 6.
Obtained nanogold thorn particle electron-microscope scanning figure is as shown in figure 9, as shown in Figure 9, the nanogold obtained in embodiment 7
Thorn particle morphology is single, and particle size is uniform, is 40~50 nanometers.
In the abosrption spectrogram such as Figure 13 of obtained gold nano thorn shown in curve b.
Embodiment 8
CTBA gold nano kind solution is 0.15mL, other identical with embodiment 6.
Obtained nanogold thorn particle electron-microscope scanning figure is as shown in Figure 10.As shown in Figure 10, what is obtained in embodiment 8 receives
Meter Jin Ci particle morphologies are single, and particle size is uniform, are 70~80 nanometers.
In the abosrption spectrogram such as Figure 13 of obtained gold nano thorn shown in curve c.
Embodiment 9
CTBA gold nano kind solution is 0.2mL, other identical with embodiment 6.
Obtained nanogold thorn particle electron-microscope scanning figure is as shown in figure 11.As shown in Figure 11, what is obtained in embodiment 9 receives
Meter Jin Ci particle morphologies are single, and particle size is uniform, are 100~150 rans.
In the abosrption spectrogram such as Figure 13 of obtained gold nano thorn shown in curve d.
Embodiment 10
CTBA gold nano kind solution is 0.25mL, other identical with embodiment 6.
Obtained nanogold thorn particle electron-microscope scanning figure is as shown in figure 12.As shown in Figure 11, what is obtained in embodiment 10 receives
Meter Jin Ci particle morphologies are single, and particle size is uniform, are 200 rans.
In the abosrption spectrogram such as Figure 13 of obtained gold nano thorn shown in curve e.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (10)
1. a kind of preparation method of gold nano thorn, including following preparation process：
1) perchloric acid gold, CTBA, sodium borohydride are mixed with water and reduction reaction occurs, obtain CTBA- gold nano kind solution；
2) perchloric acid gold, polymer template molecule and water are mixed, obtains complex solution；
3) the CTBA- gold nano kind solution for obtaining complex solution, silver nitrate, the step 1) that the step 2) obtains and
Water mixing carries out self assembly, obtains self assembly solution；
4) the self assembly solution that the step 3) obtains is mixed with ascorbic acid and carries out reduction reaction, obtain gold nano thorn；
The step 1) and step 2) do not have chronological order；
Polymer template molecule is that multiple tooth sulfydryl replaces lipoic acid-polyethylene glycol or combed polyacrylic acid-mercapto in the step 1)
Base-polyethylene glycol polymer；
The multiple tooth sulfydryl alternating lipoic acid-polyethylene glycol has structure shown in Formulas I：
The integer that the n is 40~50；
Combed polyacrylic acid-sulfydryl-the polyethylene glycol polymer has structure shown in Formula II：
The integer that the n is 40~50.
2. preparation method according to claim 1, which is characterized in that perchloric acid gold, CTBA and boron hydrogen in the step 1)
It is 1 to change the ratio between amount of substance of sodium：200~400：2~3.
3. preparation method according to claim 2, which is characterized in that CTBA- gold nanos kind solution in the step 1)
Concentration is calculated as 0.08~0.1mol/L with CTBA.
4. preparation method according to claim 1, which is characterized in that perchloric acid gold and polymer template in the step 2)
The ratio between amount of substance of molecule is 30~40：1；
The concentration of complex solution is calculated as 7~10mg/mL with polymer template molecule in the step 2).
5. preparation method according to claim 1, which is characterized in that in the step 3), the polymerization in complex solution
The ratio between amount of substance of CTBA is 1 in object template molecule, silver nitrate, CTBA- gold nano kinds：3：14~70.
6. preparation method according to claim 1, which is characterized in that in the step 4), described in ascorbic acid and preparation
The ratio between amount of substance of complex solution perchloric acid gold of self assembly solution is 1：1~2：1.
7. according to preparation method according to claim 1, which is characterized in that the multiple tooth sulfydryl replaces the poly- second of lipoic acid-
The preparation method of glycol includes the following steps：
1) compound with structure shown in formula III is subjected to coupling reaction with 2- amino -1,3 propylene glycol, obtained with formula IV
The compound of shown structure；
1) compound with formula IV structure and succinic anhydride are subjected to esterification, obtain that there is structure shown in Formula V
Compound；
2) compound with structure shown in Formula V is subjected to polycondensation reaction with the polymer with structure shown in Formula IV, is had
There is the polymer of structure shown in Formula VII；
The integer that n is 40~50 in structure shown in the Formula IV；
4) there will be Formula VII compound represented to carry out reduction reaction with sodium borohydride, obtain with multiple tooth sulfydryl shown in Formulas I
Alternately lipoic acid-polyethylene glycol.
8. according to preparation method according to claim 1, which is characterized in that the poly- second of the combed polyacrylic acid-sulfydryl-two
The preparation method of alkoxide polymer includes the following steps：
1) by the polymer with structure shown in Formula VIII and the compound with Formula IX structure and with chemical combination shown in Formula XI
Object carries out polycondensation reaction, obtains the polymer with structure shown in Formula X；
The integer that m is 20~30 in the Formula VIII；
The integer that n is 40~50 in the Formula XI；
2) polymer with structure shown in Formula X is subjected to reduction reaction with sodium borohydride, obtained with structure shown in Formula II
Combed polyacrylic acid-sulfydryl-polyethylene glycol polymer.
9. the gold nano thorn that preparation method is prepared described in claim 1~8 any one, which is characterized in that the Jenner
The pattern of rice thorn is spherical thorn-like, and the grain size of the gold nano thorn is 50nm~200nm；Contained by the gold nano thorn particle surface
The number of bayonet fittings be (5~100) it is a/particle.
10. the gold nano described in claim 9 pierces the application in photoacoustic imaging contrast agent；The contrast agent is that physiological saline is dilute
The gold nano thorn solution released, the physiological saline is 0.9% sodium-chloride water solution, a concentration of the 0.4~0.6 of the gold nano thorn
μmol/L。
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110605383A (en) * | 2019-09-30 | 2019-12-24 | 中国科学院合肥物质科学研究院 | Gold nano needle cluster material and preparation method thereof |
| CN111097038A (en) * | 2020-01-16 | 2020-05-05 | 长春工业大学 | Vancomycin-modified molybdenum disulfide/gold nanoneedle composite material and preparation method thereof |
| CN114261984A (en) * | 2020-09-25 | 2022-04-01 | 太仓沪试试剂有限公司 | Preparation method of high-activity high-purity chloroauric acid |
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| WO2011071167A1 (en) * | 2009-12-11 | 2011-06-16 | 学校法人東京理科大学 | Au-ag core-shell nanorod particles and method for producing same |
| CN104722773A (en) * | 2015-02-12 | 2015-06-24 | 苏州大学 | Preparation method of thorn-shaped gold nanoparticles and thrust-shaped gold nanoparticles prepared through method |
| CN107252896A (en) * | 2017-06-15 | 2017-10-17 | 山东大学 | A kind of synthetic method of single dispersing thorn-like gold nano grain |
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| WO2011071167A1 (en) * | 2009-12-11 | 2011-06-16 | 学校法人東京理科大学 | Au-ag core-shell nanorod particles and method for producing same |
| CN104722773A (en) * | 2015-02-12 | 2015-06-24 | 苏州大学 | Preparation method of thorn-shaped gold nanoparticles and thrust-shaped gold nanoparticles prepared through method |
| CN107252896A (en) * | 2017-06-15 | 2017-10-17 | 山东大学 | A kind of synthetic method of single dispersing thorn-like gold nano grain |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110605383A (en) * | 2019-09-30 | 2019-12-24 | 中国科学院合肥物质科学研究院 | Gold nano needle cluster material and preparation method thereof |
| CN110605383B (en) * | 2019-09-30 | 2021-08-31 | 中国科学院合肥物质科学研究院 | Gold nano needle cluster material and preparation method thereof |
| CN111097038A (en) * | 2020-01-16 | 2020-05-05 | 长春工业大学 | Vancomycin-modified molybdenum disulfide/gold nanoneedle composite material and preparation method thereof |
| CN114261984A (en) * | 2020-09-25 | 2022-04-01 | 太仓沪试试剂有限公司 | Preparation method of high-activity high-purity chloroauric acid |
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