WO2014110863A1 - Application d'un nano-agrégat d'argent et de platine pour l'imagerie ciblée d'une tumeur - Google Patents
Application d'un nano-agrégat d'argent et de platine pour l'imagerie ciblée d'une tumeur Download PDFInfo
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- WO2014110863A1 WO2014110863A1 PCT/CN2013/072344 CN2013072344W WO2014110863A1 WO 2014110863 A1 WO2014110863 A1 WO 2014110863A1 CN 2013072344 W CN2013072344 W CN 2013072344W WO 2014110863 A1 WO2014110863 A1 WO 2014110863A1
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- silver
- imaging
- platinum
- tumor
- injection
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- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 title claims abstract description 73
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 45
- 229910052697 platinum Inorganic materials 0.000 title claims abstract description 40
- 229910052709 silver Inorganic materials 0.000 title claims abstract description 39
- 239000004332 silver Substances 0.000 title claims abstract description 39
- 238000003384 imaging method Methods 0.000 title claims abstract description 30
- 238000011580 nude mouse model Methods 0.000 claims abstract description 35
- 239000000243 solution Substances 0.000 claims abstract description 33
- 239000007924 injection Substances 0.000 claims abstract description 17
- 238000002347 injection Methods 0.000 claims abstract description 17
- 238000002059 diagnostic imaging Methods 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 8
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 33
- 241000699660 Mus musculus Species 0.000 claims description 21
- 238000004113 cell culture Methods 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
- 210000003462 vein Anatomy 0.000 claims description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 238000002054 transplantation Methods 0.000 claims description 4
- 238000003332 Raman imaging Methods 0.000 claims description 3
- PLKATZNSTYDYJW-UHFFFAOYSA-N azane silver Chemical compound N.[Ag] PLKATZNSTYDYJW-UHFFFAOYSA-N 0.000 claims description 3
- 238000013170 computed tomography imaging Methods 0.000 claims description 3
- 238000000799 fluorescence microscopy Methods 0.000 claims description 3
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 3
- 239000007929 subcutaneous injection Substances 0.000 claims description 3
- 238000010254 subcutaneous injection Methods 0.000 claims description 3
- 238000001931 thermography Methods 0.000 claims description 3
- 238000012285 ultrasound imaging Methods 0.000 claims description 3
- PTNQDPSRUQFPEZ-GEMLJDPKSA-N (2s)-2-amino-5-[[(2r)-1-(carboxymethylamino)-1-oxo-3-sulfanylpropan-2-yl]amino]-5-oxopentanoic acid;silver Chemical compound [Ag].OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O PTNQDPSRUQFPEZ-GEMLJDPKSA-N 0.000 claims description 2
- 206010064571 Gene mutation Diseases 0.000 claims description 2
- 239000007927 intramuscular injection Substances 0.000 claims description 2
- 238000010255 intramuscular injection Methods 0.000 claims description 2
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 2
- 230000002269 spontaneous effect Effects 0.000 claims description 2
- 238000007920 subcutaneous administration Methods 0.000 claims description 2
- 210000000683 abdominal cavity Anatomy 0.000 claims 1
- 239000001963 growth medium Substances 0.000 claims 1
- 238000011081 inoculation Methods 0.000 claims 1
- 238000004451 qualitative analysis Methods 0.000 abstract 1
- 238000004445 quantitative analysis Methods 0.000 abstract 1
- 239000002245 particle Substances 0.000 description 8
- 239000002609 medium Substances 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 239000002086 nanomaterial Substances 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- RWSXRVCMGQZWBV-PHDIDXHHSA-N L-Glutathione Natural products OC(=O)[C@H](N)CCC(=O)N[C@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-PHDIDXHHSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- -1 platinum ions Chemical class 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000011953 bioanalysis Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000012632 fluorescent imaging Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 239000012216 imaging agent Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000005543 nano-size silicon particle Substances 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
Images
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
- A61K49/0002—General or multifunctional contrast agents, e.g. chelated agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0065—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the luminescent/fluorescent agent having itself a special physical form, e.g. gold nanoparticle
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0409—Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is not a halogenated organic compound
- A61K49/0414—Particles, beads, capsules or spheres
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
- A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
-
- 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
Definitions
- the invention relates to the application of silver and platinum nanoclusters as tumor imaging agents in tumor targeted imaging, and the invention is applicable to the field of medical imaging.
- In vivo bioimaging technology is a powerful means to detect molecular and cellular events in experimental animals. It is being used more and more widely in medical and biological research fields. It has extremely high detection sensitivity and low cost of experimentation. It can be extremely short. The application of as few animals as possible within the time can accurately obtain the expected experimental results, providing researchers with a wide application space, but the technology still has many limitations, especially the tissue autofluorescence generated during in vivo illumination. Weak tissue permeability under the excitation of broken wave excitation light.
- inorganic luminescent nanomaterials such as silicon nanoparticles
- Some inorganic nanomaterials, such as silicon nanoparticles have been widely used in bioanalysis and imaging due to some excellent properties, but there are still some problems.
- the most important thing is the particle size of nanoparticles. size. The smaller the particle size, the less likely the particles are to be absorbed by the epithelial network system and the easier it is to be excreted through the urinary system for better biocompatibility.
- nanomaterials with small particle size are more easily passively targeted to tumor sites by EPR effect to achieve precise localization of tumors.
- Chinese patent CN102735752A discloses the application of gold nanoclusters in tumor-targeted living imaging. There is no literature on the application of silver and platinum nanoclusters to tumor-targeted imaging.
- the object of the present invention is to provide an application of silver and platinum nanoclusters with small particle size and good biocompatibility in tumor targeted imaging.
- the principle of the present invention is that a certain concentration of silver and platinum ions can synthesize nanoclusters in vivo and enrich in tumor sites, and the tumor sites can be detected by medical imaging.
- the application steps of silver and platinum nanoclusters in tumor targeted imaging are:
- the culture solution containing 0.1-100 ⁇ mol/L silver-containing solution or platinum-containing solution is incubated with cells or tissues cultured for 24 hours in a cell culture incubator for 10 to 72 hours, and silver or platinum nanoclusters can be formed in the culture solution, and the culture solution is formed.
- the silver or platinum nanoclusters can be finely dispersed by ultrasonic disperser to make the silver or platinum nanocluster particles finer, and the nano-cluster particles can be more evenly distributed in nude mice when injected into nude mice;
- Direct injection of silver-containing solution or platinum-containing solution into nude mice can synthesize nano-clusters in nude mice and enrich in tumor sites, and has good biocompatibility;
- the silver-containing solution is a silver ammonia solution, a silver nitrate or a glutathione silver solution;
- the platinum-containing solution is a cis-diaminodi-platinum solution or a trans-diamino-bis-platinum solution;
- the medical imaging method is fluorescence imaging, nuclear magnetic imaging, Raman imaging, CT imaging, thermal imaging or ultrasound imaging;
- the local injection method is local subcutaneous injection, intradermal injection, intramuscular injection, tail vein injection or intraperitoneal injection;
- the nude mouse tumor model is an orthotopic transplantation tumor model, an orthotopic metastatic tumor model, a subcutaneous tumor model, a drug-induced tumor model, a gene mutation tumor model or a spontaneous tumor model.
- the silver and platinum nanoclusters prepared by the invention have small particle size, good permeability, high fluorescence stability, high sensitivity and strong targeting, and can accurately locate the tumor;
- the silver and platinum nanoclusters of the present invention are ultrasonically dispersed and injected, so that the nanoparticles are finer and more uniform, and are more favorable for absorption;
- the invention has the advantages of convenient operation and direct result, and can be used for early detection and diagnosis of tumors, and can also be applied in research on tracking and imaging of living tumors such as deep tumors and large animals, and has potential application value of clinical disease tracking treatment imaging. .
- Example 1a is a diagram showing the results of a confocal fluorescence microscope of an experimental group of Example 1 of the present invention
- Figure 1b is a graph showing the results of a confocal fluorescence microscope of the control group of Example 1 of the present invention.
- Example 2 is a diagram showing tumor targeting imaging of a nude mouse fluorescent imaging image according to Example 2 of the present invention.
- Hepatoma cells were selected as the research object.
- the experimental group inoculated liver cancer cells (HepG2) in logarithmic growth phase in a 6-well plate at a density of 1.6 ⁇ 105 cells/well. After h, a solution containing glutathione silver ammonia 1 ⁇ mol/L which had been sterilized and diluted with fresh sterile DMEM medium was added.
- the experimental results of the experimental group are shown in Figure 1a, and the experimental results of the control group are shown in Figure 1b.
- the nude mice were subcutaneously inoculated with breast cancer model.
- the breast cancer cells were cultured for 24 h and then sterilized and freshly sterile DMEM.
- the medium was diluted to 0.1 ⁇
- the mol/L glutathione silver ammonia solution was incubated in a cell culture incubator for 24 hours to prepare silver nanoclusters, and the solution containing the silver nanoclusters was ultrasonically dispersed and injected into the nude mice by tail vein injection method, 24 After h, nude mice were subjected to in vivo fluorescence imaging. Experiments show that silver nanoclusters can achieve targeted imaging of tumor sites. The experimental results are shown in Figure 2.
- the nude mouse model of orthotopic liver transplantation was constructed.
- the liver cancer cells were cultured for 24 hours and then sterilized and freshly sterile DMEM.
- the diluted medium 50 ⁇ mol/L cis-diaminodi-platinum solution was incubated in a cell culture incubator for 48 hours to prepare platinum nanoclusters.
- the solution containing platinum nanoclusters was ultrasonically dispersed and injected by topical subcutaneous injection.
- nude mice 24 After h, the nude mice were subjected to nuclear magnetic imaging and the imaging results were qualitatively and quantitatively analyzed.
- nude mouse drug-induced ovarian tumor model ovarian cancer cell culture 24 After h, a 100 ⁇ mol/L silver nitrate solution which had been sterilized and diluted with fresh sterile DMEM medium was added, and the cells were incubated in a cell culture incubator for 72 hours to prepare silver nanoclusters, and the solution containing the silver nanoclusters was ultrasonically dispersed. , injected intraperitoneally into nude mice, 24 After h, the nude mice were subjected to Raman imaging and the imaging results were qualitatively and quantitatively analyzed.
- a nude mouse model of subcutaneously inoculated breast cancer was constructed, and a 0.1 ⁇ mol/L silver ammonia solution was directly injected into the nude mice by tail vein injection. After h, the nude mice were subjected to CT imaging and the imaging results were qualitatively and quantitatively analyzed.
- nude mice Construction of a nude mouse orthotopic liver transplantation model, direct injection into the nude mice by intradermal injection of 50 ⁇ After mol/L of trans-diaminodi-platinum solution, the nude mice were subjected to thermal imaging and the imaging results were qualitatively and quantitatively analyzed.
- nude mice Construction of a nude mouse drug-induced ovarian tumor model, direct injection of 100 ⁇ mol/L glutathione silver solution into the nude mice by tail vein injection, 24 After h, the nude mice were subjected to ultrasound imaging and the imaging results were qualitatively and quantitatively analyzed.
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- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Radiology & Medical Imaging (AREA)
- Inorganic Chemistry (AREA)
- Acoustics & Sound (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Nanotechnology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
L'invention concerne l'application d'un nano-agrégat d'argent et de platine pour l'imagerie ciblée d'une tumeur comprenant les étapes consistant à établir un modèle tumoral chez une souris nude; à injecter localement un nano-agrégat d'argent ou de platine dispersé par ultrasons dans une souris nude, ou à injecter directement une solution contenant de l'argent ou du platine (0,1 à 100 μmol/L) dans une souris nude; puis, 24 heures après l'injection, à réaliser une imagerie médicale sur la partie tumorale de la souris nude au moyen d'un procédé d'imagerie médicale, puis à réaliser une analyse qualitative et quantitative du résultat de l'imagerie.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310015357.2A CN103083687B (zh) | 2013-01-16 | 2013-01-16 | 一种银、铂纳米簇在肿瘤靶向成像的应用 |
| CN201310015357.2 | 2013-01-16 |
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| Publication Number | Publication Date |
|---|---|
| WO2014110863A1 true WO2014110863A1 (fr) | 2014-07-24 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2013/072344 WO2014110863A1 (fr) | 2013-01-16 | 2013-03-08 | Application d'un nano-agrégat d'argent et de platine pour l'imagerie ciblée d'une tumeur |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN103083687B (fr) |
| WO (1) | WO2014110863A1 (fr) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111592875A (zh) * | 2020-02-08 | 2020-08-28 | 安徽师范大学 | 一种荧光纤维素酶铂纳米簇及制备方法和应用 |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103861124B (zh) * | 2014-03-03 | 2016-09-21 | 东南大学 | 铂纳米簇的制备方法及在肿瘤的成像剂和凋亡剂中的应用 |
| CN105214103B (zh) * | 2015-10-14 | 2018-04-24 | 东南大学 | 用于恶性肿瘤和心脑血管相关疾病早期快速检测及多模态成像的金属离子试剂和影像制剂 |
| CN107184981A (zh) * | 2017-06-08 | 2017-09-22 | 浙江大学 | 一种片状三角形银纳米粒抗菌悬浮液及其制备方法和应用 |
| CN107884377B (zh) * | 2017-11-24 | 2020-09-11 | 东南大学 | 基于细胞外泌体纳米簇探针及其在制备成像制剂中的应用 |
| CN108865147B (zh) * | 2018-06-01 | 2021-05-18 | 福州大学 | 一种埃罗替尼保护的铂银纳米簇及其制备方法 |
| CN109266333B (zh) * | 2018-10-23 | 2020-06-12 | 山西大学 | 一种荧光银纳米团簇探针的制备方法和应用 |
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| CN1909931A (zh) * | 2004-01-15 | 2007-02-07 | 皇家飞利浦电子股份有限公司 | 用于分子成像的超声造影剂 |
| CN102203002A (zh) * | 2007-09-21 | 2011-09-28 | 细胞免疫科学公司 | 纳米治疗性胶态金属组合物和方法 |
| CN102703060A (zh) * | 2012-06-08 | 2012-10-03 | 中国药科大学 | 一种靶向特性的可示踪贵金属荧光探针及抗肿瘤前药 |
| CN102735752A (zh) * | 2012-06-11 | 2012-10-17 | 东南大学 | 基于金纳米簇的肿瘤靶向活体多模态成像方法 |
-
2013
- 2013-01-16 CN CN201310015357.2A patent/CN103083687B/zh active Active
- 2013-03-08 WO PCT/CN2013/072344 patent/WO2014110863A1/fr active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1909931A (zh) * | 2004-01-15 | 2007-02-07 | 皇家飞利浦电子股份有限公司 | 用于分子成像的超声造影剂 |
| CN102203002A (zh) * | 2007-09-21 | 2011-09-28 | 细胞免疫科学公司 | 纳米治疗性胶态金属组合物和方法 |
| CN102703060A (zh) * | 2012-06-08 | 2012-10-03 | 中国药科大学 | 一种靶向特性的可示踪贵金属荧光探针及抗肿瘤前药 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111592875A (zh) * | 2020-02-08 | 2020-08-28 | 安徽师范大学 | 一种荧光纤维素酶铂纳米簇及制备方法和应用 |
| CN111592875B (zh) * | 2020-02-08 | 2023-04-18 | 安徽师范大学 | 一种荧光纤维素酶铂纳米簇及制备方法和应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103083687A (zh) | 2013-05-08 |
| CN103083687B (zh) | 2016-04-13 |
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