CN106692995A - Polydopamine coated gold nanorod material as well as preparation method and application of polydopamine coated gold nanorod material - Google Patents
Polydopamine coated gold nanorod material as well as preparation method and application of polydopamine coated gold nanorod material Download PDFInfo
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- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 title claims abstract description 88
- 239000000463 material Substances 0.000 title claims abstract description 58
- 229920001690 polydopamine Polymers 0.000 title claims abstract description 47
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 210000004027 cell Anatomy 0.000 claims abstract description 54
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 35
- 238000006243 chemical reaction Methods 0.000 claims abstract description 24
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 21
- 230000000694 effects Effects 0.000 claims abstract description 21
- 238000003384 imaging method Methods 0.000 claims abstract description 17
- 238000001514 detection method Methods 0.000 claims abstract description 14
- 238000007626 photothermal therapy Methods 0.000 claims abstract description 12
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 claims abstract description 9
- 238000001069 Raman spectroscopy Methods 0.000 claims description 54
- 239000000243 solution Substances 0.000 claims description 38
- 238000005253 cladding Methods 0.000 claims description 32
- 230000004048 modification Effects 0.000 claims description 14
- 238000012986 modification Methods 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- 230000009514 concussion Effects 0.000 claims description 9
- 229910052737 gold Inorganic materials 0.000 claims description 9
- 239000010931 gold Substances 0.000 claims description 9
- RADLTTWFPYPHIV-UHFFFAOYSA-N (2-sulfanylphenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1S RADLTTWFPYPHIV-UHFFFAOYSA-N 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 8
- 238000003786 synthesis reaction Methods 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 7
- SJUCACGNNJFHLB-UHFFFAOYSA-N O=C1N[ClH](=O)NC2=C1NC(=O)N2 Chemical compound O=C1N[ClH](=O)NC2=C1NC(=O)N2 SJUCACGNNJFHLB-UHFFFAOYSA-N 0.000 claims description 6
- 239000011521 glass Substances 0.000 claims description 6
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 230000008878 coupling Effects 0.000 claims description 5
- 238000010168 coupling process Methods 0.000 claims description 5
- 238000005859 coupling reaction Methods 0.000 claims description 5
- 239000003550 marker Substances 0.000 claims description 5
- 125000004151 quinonyl group Chemical group 0.000 claims description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- 239000006143 cell culture medium Substances 0.000 claims description 4
- 229960003638 dopamine Drugs 0.000 claims description 4
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 claims description 3
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 claims description 3
- 239000007983 Tris buffer Substances 0.000 claims description 3
- 239000001963 growth medium Substances 0.000 claims description 3
- 238000011534 incubation Methods 0.000 claims description 3
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 238000004113 cell culture Methods 0.000 claims description 2
- 230000008859 change Effects 0.000 claims description 2
- 238000007689 inspection Methods 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 230000000007 visual effect Effects 0.000 claims description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 229910052796 boron Inorganic materials 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 238000011017 operating method Methods 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 230000005284 excitation Effects 0.000 abstract description 3
- 238000003332 Raman imaging Methods 0.000 abstract 1
- 238000001530 Raman microscopy Methods 0.000 abstract 1
- 238000002474 experimental method Methods 0.000 abstract 1
- 230000002035 prolonged effect Effects 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 238000005516 engineering process Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 206010060862 Prostate cancer Diseases 0.000 description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 3
- 238000013007 heat curing Methods 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 241000209094 Oryza Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 2
- -1 alkyl trimethyl ammonium bromides Chemical class 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000001045 blue dye Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 238000011895 specific detection Methods 0.000 description 2
- 238000007669 thermal treatment Methods 0.000 description 2
- GDSOZVZXVXTJMI-SNAWJCMRSA-N (e)-1-methylbut-1-ene-1,2,4-tricarboxylic acid Chemical compound OC(=O)C(/C)=C(C(O)=O)\CCC(O)=O GDSOZVZXVXTJMI-SNAWJCMRSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical group OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 1
- 238000013170 computed tomography imaging Methods 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960004502 levodopa Drugs 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000004416 surface enhanced Raman spectroscopy Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- 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
- A61K49/221—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by the targeting agent or modifying agent linked to the acoustically-active agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
-
- 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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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Physics & Mathematics (AREA)
- Acoustics & Sound (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Radiation-Therapy Devices (AREA)
Abstract
The invention belongs to the technical field of biology, and in particular relates to a polydopamine coated gold nanorod material as well as a preparation method and application of the polydopamine coated gold nanorod material. The preparation method disclosed by the invention comprises the following steps: by taking CTAB (cetyl trimethyl ammonium bromide) as a template agent, synthesizing a polydopamine coated gold nanorod material; modifying an antibody onto the surface of the material, thereby obtaining a multifunctional polydopamine coated gold nanorod material. Thus, a tumor cell Raman imaging detection and real-time photothermal therapy platform is constructed. The experiments prove that the gold nanorod material is capable of realizing specific effective tumor target cell marking and performing rapid surface-enhanced Raman spectral imaging scanning on the tumor cells under excitation of near-infrared light; and the tumor target cells are accurately identified by the imaging results, and after the target cells are identified, the infrared light can be focused onto the tumor target cells, the irradiation time is prolonged, and the material is heated by utilizing the photo-thermal conversion effect of the gold nanorod material so as to kill the tumor cells in real time. The polydopamine coated gold nanorod material disclosed by the invention is novel, convenient, practical and efficient and has huge clinical application potential.
Description
Technical field
The invention belongs to biological technical field, and in particular to the gold nanorods material of poly-dopamine cladding and its preparation side
Method, and applied in the detection of tumour cell Raman image and real-time photo-thermal therapy platform is built.
Background technology
Imaging guiding is a tumour cell detection for quickly growing and treatment technology, is to realize the one of precisely medical treatment in future
The important means of item.In the oncotherapy technology of imaging guiding, photo-thermal therapy is due to its high efficiency, minimal invasive and to surrounding
Low damaging advantage is organized, it is of increased attention.In recent years, with it is various and meanwhile have photothermal conversion efficiency with
And the multi-functional nanometer material of image sensitivity high is constantly synthesized, people have developed the tumour light of various different imaging guiding
Heat cure technology.Because the laser for being imaged different with photo-thermal therapy needs is excited, so the tumour light of these imaging guiding
Heat cure technology generally requires being used in combination for various instruments could be completed, not only complex steps, and reduce oncotherapy
Specificity, limit its application in clinic.
Gold nanorods have strong absorption near infrared region, and are photo-thermal therapies with good photothermal conversion efficiency
In commonly use a kind of nano material.Additionally, gold nanorods also have many unique optical properties, widely should as developer
In for the tumor imaging of various modes, such as near infrared light imaging, NMR imaging, CT imagings and Raman image.At these
In imaging pattern, Raman image, particularly surface-enhanced Raman（SERS）Imaging, because with high sensitivity, good
A kind of ability that photostability and multiple target are detected simultaneously, it is considered to be preferable tumor imaging detection means.It is worth noting
, gold nanorods can simultaneously produce photothermal conversion effect and Raman enhancement effect under the exciting of near infrared light.Jenner
This unique optical property of the rice rod under near-infrared excitation light is the detection of exploitation tumour cell Raman image and real-time photo-thermal
Treatment unified platform is provided may.
Cetyl trimethylammonium bromide（CTAB）Be gold nanorods material building-up process in a kind of conventional template
Molecule.However, CTAB molecules have strong cytotoxicity, must go to remove before gold nanorods are applied to Bioexperiment.It is poly-
Dopamine is a kind of polymer macromolecule of dopamine monomer molecule auto polymerization in the basic conditions, with good bio-compatible
Property, there is good stability in saline, the catechol group on its surface can change under weak basic condition
It is quinonyl, by quinonyl with the amino of albumen end or the coupled action of sulfydryl, the protein moleculars such as antibody can be connected to poly-
Dopamine surface.Any other anakmetomeres need not be added in this process, can to greatest extent keep antibody point
The bioactivity of son.
In order to realize the specific detection of tumour and effectively treatment, the present invention devises the gold based on poly-dopamine cladding
The detection of tumour cell Raman image and the real-time photo-thermal therapy unified platform of nanometer rods, simplify the step of lesion detection and treatment
Suddenly, the specificity and effect of lesion detection and treatment are improve, the damage to health tissues is further reduced.Experimental result shows
Show, the unified platform has huge clinical practice potentiality.
The content of the invention
Gold nanorods material it is an object of the invention to provide a kind of poly-dopamine cladding and preparation method thereof, Yi Ji
Applied in the detection of structure tumour cell Raman image and real-time photo-thermal therapy platform.
The preparation method of the gold nanorods of poly-dopamine cladding proposed by the present invention, comprises the following steps that：
（1）The synthesis of gold nano seed：At room temperature, by 1-10mL chlorauric acid solutions（0.5-1mM）With 1-10mL CTAB solution
（0.2-0.5 M）Fully mix, be subsequently added the sodium borohydride solution of 0.5-1mL precoolings（0.01-0.05 M）, 28-37 DEG C is kept away
Light reaction 2-5 hours, obtain the gold nano seed solution of brown；
（2）Gold nanorods（Length-width ratio 3-5）Synthesis：By 1-10mL chlorauric acid solutions（1-2 mM）With 1-10mLCTAB solution
（0.2-0.5M）Fully mix, add 0.1-0.5 mL silver nitrate solutiones（5-20mM）Fully mix, add 0.05-0.1 mL to resist
Bad hematic acid solution（0.1-0.2 M, matching while using）Fully mix, add 0.01-0.02 mL steps（1）The gold nano of middle synthesis
Seed solution, 28-37 DEG C of reaction overnight, obtains the gold nanorods material that length-width ratio is 3-5,8000- after fully mixing
10000rpm is centrifuged, and washes with water 2-3 times；
（3）Gold nanorods surface poly-dopamine cladding：Gold nanorods material after washing is dissolved in Tris cushioning liquid again
（10-20mM, pH8.0-10.0）, 0.01-0.02 mL are added to mercaptophenyl boronic acid solution（10-20 mM）, concussion reaction 1-2 is small
When, it is subsequently added 0.05-0.02mL dopamine solutions（1-2 mg/mL）, 28-37 DEG C of concussion reaction overnight, obtain poly-dopamine
The gold nanorods material of cladding；
（4）The modification of antibody：Using the method for quinonyl covalent coupling by epithelial cell adhesion molecule antibody（anti-EpCAM）Repair
Adorn in gold nanorods material surface, the gold nanorods material that poly-dopamine is coated is dissolved in PBS cushioning liquid again（0.02-
0.05 mMmM）, add 0.02-0.05mL antibody-solutions, 25-37 DEG C of coupling 12-20 h, will antibody modification to gold nanorods
Material surface, and use bovine serum albumin(BSA)（BSA）Blocked, be capable of achieving the specific marker to tumour target cell.
The gold nanorods material of present invention synthesis, the modification of poly-dopamine can effectively coat the ten of gold nanorods surface
Six alkyl trimethyl ammonium bromides（CTAB）Molecule, and then the biocompatibility and stability of gold nanorods material are improve, this gathers
The gold nanorods material of dopamine cladding is in near-infrared laser（785nm）Exciting under, while having good surface enhanced to draw
Graceful effect and photothermal conversion effect, after poly-dopamine surface modification antibody, material can realize the spy to tumour target cell
Opposite sex mark.
Just because of above-mentioned gold nanorods material has special performance, so can be used to build the inspection of tumour cell Raman image
Survey includes with real-time photo-thermal therapy platform, the platform：
Cell culture medium, for incubated cell；
The gold nanorods solution of the poly-dopamine cladding of antibody modification, in near-infrared laser（785nm）Exciting under, surface
Enhancing Ramam effect and photothermal conversion effect, and as tumor target cell specific marker；
Raman microscope objective table, for placing cell culture vessel；
It is equipped with near-infrared laser（785nm）Raman image microscope, wherein, Raman image microscope be used for cell is carried out
Fast Raman is scanned, and using the characteristic Raman signals peak to mercaptophenyl boronic acid（1080cm-1）Signal intensity be imaged, into
As the position of result tumor cells showed；Near-infrared laser（785nm）For irradiated tumor cell, using the photo-thermal of gold nanorods
Conversion effet makes material warms, necrotic tumor cells.
The detection of tumour cell Raman image and the real-time photo-thermal therapy platform of above-mentioned structure, specifically used method are as follows：
（1）Material and cell incubation：10 are added in Glass bottom culture dish first5-106The cell of/mL, uses cell culture medium culture
Overnight, grow cell attachment.The gold nanorods solution of the poly-dopamine cladding of 10-30 μ L antibody modifications is taken, culture dish is added
In, slight concussion is incubated 1-2 h under the conditions of 37 DEG C, discards upper strata culture medium, after washing three times with PBS, and addition 100-
The PBS of 200uL；
（2）Tumour Raman image：Glass bottom culture dish is positioned on Raman microscope objective table, adjusting focal length allows cell clear
Clear is apparent in the visual field, selects suitable exciting light（785nm）And corresponding test parameter is adjusted, using Raman microscope point
The method of scanning carries out fast Raman scanning to cell, using the characteristic Raman signals peak to mercaptophenyl boronic acid（1080cm-1）'s
Signal intensity is imaged, the position of imaging results tumor cells showed；
（3）Photo-thermal is killed：According to Raman image result, by laser fixed point to tumor cell surface（1-2 minutes/each cell）,
Extend the laser irradiation time to target cell（4-5 minutes/each cell）, the photothermal conversion effect using gold nanorods makes material
Heat up, and then cause meronecrosis, reach the effect of tumour cell photo-thermal killing.
The tumour cell Raman image detection of the gold nanorods based on poly-dopamine cladding that the present invention is provided and Real-Time Optical
Heat cure unified platform, using near-infrared laser（785nm）As exciting light, quick spot scan is carried out to tumor tissues
（1-2 minutes each cell）, the particular location of tumour cell can be rapidly and accurately identified by Raman image figure.Then,
Using near-infrared laser（785nm）Fixed point irradiated tumor cell, extends irradiation time（4-5 minutes each cell）, by Jenner
The photothermal conversion effect of rice rod realizes that the real-time photo-thermal of tumour cell is killed.Due to gold nanorods surface-enhanced Raman effects and
Photothermal conversion effect can be in near-infrared laser（785nm）Exciting under generation, therefore only need to one and be equipped with near-infrared
Laser（785nm）Raman image microscope, tumour target cell can be gone out with accurate discrimination according to Raman image result, then only need
Extend irradiation time of the exciting light to tumour cell, just can realize that the photo-thermal of tumour cell is killed.
Main advantage of the invention is simple and effective, it is possible to achieve the specific detection of tumour cell and real-time photo-thermal
Treatment, it is to avoid because lesion detection it is different with therapeutic equipments caused by tedious steps, further damage of the reduction to healthy cell
Wound, can improve the validity and specificity of tumour cell treatment.
Brief description of the drawings
The gold nanorods transmission electron microscope picture of Fig. 1 poly-dopamines cladding.Wherein, A is gold nanorods electron microscope under low power lens；B
It is gold nanorods electron microscope under high power lens；C is the gold nanorods electron microscope of poly-dopamine cladding under low power lens；D is under high power lens
The gold nanorods electron microscope of poly-dopamine cladding.
Heating curve figure of the gold nanorods material of Fig. 2 poly-dopamines cladding under infrared excitation irradiation.
Fig. 3 gold nanorods are contrasted with the surface-enhanced Raman effects of the gold nanorods material of poly-dopamine cladding.
Fig. 4 gold nanorods are contrasted with the gold nanorods Biocompatibility of poly-dopamine cladding.
Stability contrast of the gold nanorods material that Fig. 5 gold nanorods are coated with poly-dopamine in PBS solution.
The gold nanorods material of Fig. 6 poly-dopamines cladding is to prostate cancer target cell（DU145）And compared with control cells
（U251）Mark and Raman image.Wherein, A is DU145 cells under light field microscope；B is the Raman image of DU145 cells
Figure；C is U251 cells under light field microscope；D is the Raman image figure of U251 cells.
Mark and Raman image of the gold nanorods material of Fig. 7 poly-dopamines cladding to prostate tumor tissue.Wherein,
A left sides are the tumor tissue section without HE dyeing, and wherein dashed rectangle part is the region of Raman image scanning, and right side is to draw
Graceful image；B is the tumor tissue section after HE dyeing, and wherein dashed rectangle part is the region of Raman image scanning, right side
It is the HE dye images in Raman image region.
The gold nanorods material of Fig. 8 poly-dopamines cladding is to prostate cancer target cell（DU145）And compared with control cells
（U251）Photo-thermal Mortaility results.
The gold nanorods material of Fig. 9 poly-dopamines cladding is to prostate cancer target cell（DU145）Mark, Raman image with
And photo-thermal is killed.Wherein, A is the DU145 cell light field figures before Raman scanning；B is the Raman image figure of DU145 cells；C is platform
The result that trypan blue dye is dyeed to DU145 cells after imaging；D is after Trypan Blue dye excites light irradiation to long-time
The result that DU145 cells are dyeed.
Specific embodiment
Embodiment 1：The gold nanorods materials synthesis of the poly-dopamine cladding of antibody modification
At room temperature, by 5mL chlorauric acid solutions（0.5 mM）With 5mLCTAB solution（0.2 M）Fully mix, be subsequently added
The sodium borohydride solution of 0.6mL precoolings（0.01 M）, 28 DEG C of lucifuges react 2 hours, obtain the gold nano seed solution of brown.Will
5mL chlorauric acid solutions（1 mM）With 5mLCTAB solution（0.2 M）Fully mix, add 0.12mL silver nitrate solutiones（10mM）Fill
Divide and mix, add 0.055mL ascorbic acid solutions（0.1M, matching while using）Fully mix, add 0.012mL steps（1）Middle conjunction
Into gold nano seed solution, fully mix after 28 DEG C reaction overnight, obtain the gold nanorods material that length-width ratio is 3.8,
8000rpm is centrifuged, and washes with water twice.Gold nanorods material after washing is dissolved in Tris cushioning liquid again（10mM,
pH8.0）, 0.01mL is added to mercaptophenyl boronic acid solution（10mM）, concussion reaction 1 hour is subsequently added 0.05-0.02mL DOPA
Amine aqueous solution（1mg/mL）, 37 DEG C of concussion reactions overnight, obtain poly-dopamine cladding gold nanorods material.It is covalently even using quinonyl
The method of connection is by epithelial cell adhesion molecule antibody（anti-EpCAM）Modify in gold nanorods material surface, by poly-dopamine bag
The gold nanorods material for covering is dissolved in PBS cushioning liquid again（0.02mM）, add 0.02mL antibody-solutions, 25-37 DEG C of coupling
Antibody modification to gold nanorods material surface can be capable of achieving the specific marker to tumour target cell after 12-20 h.
Embodiment 2：The tumour cell Raman image detection of the gold nanorods based on poly-dopamine cladding is controlled with real-time photo-thermal
Unified platform is treated in prostate gland cancer cell（DU145）Application in Raman image and photo-thermal therapy.
About 10 are added in Glass bottom culture dish first5The cell of/mL, overnight incubation grows cell attachment.Take 10-30
The gold nanorods solution of the poly-dopamine cladding of μ L antibody modifications, adds in culture dish, and slight concussion is incubated 1-2 under the conditions of 37 DEG C
H, discards upper strata culture medium, after washing three times with PBS, and adds the PBS of 100 uL.
Glass bottom culture dish is positioned on Raman microscope objective table, adjusting focal length allows cell to be clearly apparent in regard
Yezhong, selects suitable exciting light（785nm）And corresponding test parameter is adjusted, using the method pair of Raman microscope spot scan
Cell carries out fast Raman scanning, using the characteristic Raman signals peak to mercaptophenyl boronic acid（1080cm-1）Signal intensity carry out
Imaging, imaging results show the position of tumour cell.
According to Raman image result, by exciting light fixed point to tumor cell surface, when extension is irradiated to the laser of target cell
Between, make material warms using the photothermal conversion effect of gold nanorods, and then cause meronecrosis, reach the killing of tumour cell photo-thermal
Effect.
Claims (4)
1. the preparation method of the gold nanorods material of a kind of poly-dopamine cladding, it is characterised in that comprise the following steps that：
（1）The synthesis of gold nano seed：At room temperature, by 1-10mL concentration for the chlorauric acid solution of 0.5-1 mM is dense with 1-10mL
Spend for the CTAB solution of 0.2-0.5 M is fully mixed, be subsequently added the boron hydrogen of the precooling that 0.5-1mL concentration is 0.01-0.05 M
Change sodium solution, 28-37 DEG C of lucifuge is reacted 2-5 hours, obtains the gold nano seed solution of brown；
（2）The synthesis of gold nanorods：By 1-10mL concentration for the chlorauric acid solution of 1-2 mM is 0.2-0.5M with 1-10mL concentration
CTAB solution fully mix, add 0.1-0.5 mL concentration fully to be mixed for the silver nitrate solution of 5-20mM, add 0.05-
0.1 mL concentration is fully mixed for the ascorbic acid solution of 0.1-0.2 M, adds 0.01-0.02 mL steps（1）The gold of middle synthesis
Nanometer seed solution, 28-37 DEG C of reaction overnight, obtains the gold nanorods material that length-width ratio is 3-5,8000- after fully mixing
10000rpm is centrifuged, and washes with water 2-3 times；
（3）Gold nanorods surface poly-dopamine cladding：Gold nanorods material after washing is dissolved in concentration for 10-20mM, pH again
It is worth in the Tris cushioning liquid for 8.0-10.0, it is the molten to mercaptophenyl boronic acid of 10-20 mM to add 0.01-0.02 mL concentration
Liquid, concussion reaction 1-2 hours, is subsequently added the dopamine solution that 0.05-0.02mL concentration is 1-2 mg/mL, 28-37 DEG C of concussion
Reaction overnight, obtains the gold nanorods material of poly-dopamine cladding；
（4）The modification of antibody：Using the method for quinonyl covalent coupling by epithelial cell adhesion molecule antibody modification in gold nanorods
Material surface, concentration is dissolved in in 0.02-0.05 mM PBS cushioning liquid by the gold nanorods material that poly-dopamine is coated again,
Add 0.02-0.05 mL antibody-solutions, 25-37 DEG C coupling 12-20 h, will antibody modification to gold nanorods material surface,
It is capable of achieving the specific marker to tumour target cell.
2. the gold nanorods material that the poly-dopamine for being obtained as preparation method described in claim 1 is coated.
3. a kind of tumour cell Raman image detection of the gold nanorods material of the poly-dopamine cladding based on described in claim 2
With real-time photo-thermal therapy platform, it is characterised in that the platform includes：
Cell culture medium, for incubated cell；
The gold nanorods solution of the poly-dopamine cladding of antibody modification, under the exciting of near-infrared laser, surface enhanced to draw
Graceful effect and photothermal conversion effect, and as tumor target cell specific marker；
Raman microscope objective table, for placing cell culture vessel；
The Raman image microscope of near-infrared laser is equipped with, wherein, Raman image microscope is used to quickly draw cell
Graceful scanning, and signal intensity using the characteristic Raman signals peak to mercaptophenyl boronic acid is imaged, imaging results display tumour
The position of cell；Near-infrared laser is used for irradiated tumor cell, and the photothermal conversion effect using gold nanorods makes material warms, bad
Dead tumour cell.
4. a kind of tumour cell Raman image inspection of the gold nanorods material based on poly-dopamine cladding as claimed in claim 3
Survey the operating method with real-time photo-thermal therapy platform, it is characterised in that comprise the following steps that：
（1）Material and cell incubation：About 10 are added in Glass bottom culture dish first5-106The cell of/mL, is trained with cell culture medium
Support overnight, grow cell attachment；The gold nanorods solution of the poly-dopamine cladding of 10-30 μ L antibody modifications is taken, culture is added
In ware, slight concussion is incubated 1-2 h under the conditions of 37 DEG C, discards upper strata culture medium, after washing three times with PBS, and addition 100-
The PBS of 200 μ L；
（2）Tumour Raman image：Glass bottom culture dish is positioned on Raman microscope objective table, adjusting focal length allows cell clear
Clear is apparent in the visual field, selects suitable exciting light and adjusts corresponding test parameter, using Raman microscope spot scan
Method carries out fast Raman scanning to cell, is carried out into using the signal intensity at the characteristic Raman signals peak to mercaptophenyl boronic acid
Picture, the position of imaging results tumor cells showed；
（3）Photo-thermal is killed：According to Raman image result, by laser fixed point to tumor cell surface, 1-2 minutes/each cell, prolong
Laser irradiation time to target cell long, 4-5 minutes/each cell, the photothermal conversion effect using gold nanorods made material liter
Temperature, and then cause meronecrosis, reach the effect of tumour cell photo-thermal killing.
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