WO2014110863A1 - Application of silver and platinum nano-cluster in tumor targeted imaging - Google Patents
Application of silver and platinum nano-cluster in tumor targeted imaging 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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- 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
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- 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
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- 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
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- 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
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- 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
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- 239000007927 intramuscular injection Substances 0.000 claims description 2
- 238000010255 intramuscular injection Methods 0.000 claims description 2
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- 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
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- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
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- 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
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- A—HUMAN NECESSITIES
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- A61K49/00—Preparations for testing in vivo
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- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
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- 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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Abstract
An application of a silver and platinum nano-cluster in tumor targeted imaging comprises the steps of: establishing a nude mouse tumor model; locally injecting an ultrasonically dispersed silver or platinum nano-cluster into a nude mouse, or directly injecting a silver or platinum containing solution of 0.1 to 100 μmol/L into a nude mouse; and in 24 hours after injection, performing medical imaging on the tumor part of the nude mouse by using a medical imaging method, and performing qualitative and quantitative analysis on the imaging result.
Description
本发明涉及银、铂纳米簇作为肿瘤成像剂在肿瘤靶向成像上的应用，本发明适用于医学成像领域。 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.
活体生物成像技术是检测实验动物体内分子及细胞事件的强有力手段，正在被越来越广泛地应用于医学及生物学研究领域，具有极高的检测灵敏度及低廉的实验费用，可以在极短的时间内应用尽可能少的动物数量却可精确获得预期的实验结果，为研究者提供了广阔的应用空间，但该技术仍然存在许多局限性，尤其是在体内光照时产生的组织自发荧光和在断波激发光照射下的弱的组织渗透性。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.
为了克服这些困难。科学家研究了一系列无机发光纳米材料，一些无机纳米材料，如硅纳米颗粒由于其一些优良的性质在生物分析和成像中得到广泛应用，但仍存在一些问题，最重要的就是纳米颗粒的粒径大小。颗粒粒径越小，颗粒被上皮网状组织系统吸收的几率就越小，且更容易通过泌尿系统排出体外，从而具有更好的生物相容性。另外，当对肿瘤进行靶向成像时，粒径小的纳米材料更容易通过EPR效应被动靶向到肿瘤部位从而实现对肿瘤的精确定位。In order to overcome these difficulties. Scientists have studied a series of inorganic luminescent nanomaterials. 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. In addition, when targeting tumors, nanomaterials with small particle size are more easily passively targeted to tumor sites by EPR effect to achieve precise localization of tumors.
中国专利CN102735752A公开了金纳米簇在肿瘤靶向活体成像上的应用，目前还没有银、铂纳米簇应用于肿瘤靶向成像的文献资料。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.
本发明的目的在于提供一种粒径小、生物相容性好的银、铂纳米簇在肿瘤靶向成像上的应用。 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.
本发明的原理是一定浓度的银、铂离子可以在生物体内合成纳米簇并且在肿瘤部位富集，通过医学成像可以检测诊断肿瘤部位。具体来说，银、铂纳米簇在肿瘤靶向成像上的应用步骤为：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. Specifically, the application steps of silver and platinum nanoclusters in tumor targeted imaging are:
（1）构建裸鼠肿瘤模型；(1) Constructing a nude mouse tumor model;
（2）向裸鼠体内局部注射经超声分散的银或铂纳米簇，或者直接注射0.1-100µmol/L含银溶液或含铂溶液；(2) locally injecting ultrasonically dispersed silver or platinum nanoclusters into nude mice, or directly injecting 0.1-100 μmol/L silver-containing solution or platinum-containing solution;
（3）注射24h后，用医学成像方法对裸鼠肿瘤部位进行医学成像并对成像结果进行定性及定量分析；(3) After 24 hours of injection, medical imaging was performed on the tumor site of nude mice and the imaging results were qualitatively and quantitatively analyzed.
将含有0.1-100µmol/L含银溶液或含铂溶液的培养液与培养24h的细胞或组织于细胞培养箱中共同孵育10-72小时，培养液中可形成银或铂纳米簇，将培养液中的银或铂纳米簇经超声分散仪超声分散后可使银或铂纳米簇颗粒更细，注射至裸鼠体内可使纳米簇颗粒在裸鼠体内分布更均匀；The culture solution containing 0.1-100 μmol/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;
直接向裸鼠体内注射含银溶液或含铂溶液，可在裸鼠体内合成纳米簇并且在肿瘤部位富集，具有良好的生物相容性；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;
所述的含银溶液为银氨溶液、硝酸银或谷胱甘肽银溶液；The silver-containing solution is a silver ammonia solution, a silver nitrate or a glutathione silver solution;
所述的含铂溶液为顺式二氨基二络铂溶液或反式二氨基二络铂溶液；The platinum-containing solution is a cis-diaminodi-platinum solution or a trans-diamino-bis-platinum solution;
所述的医学成像方法为荧光成像、核磁成像、拉曼成像、CT成像、热成像或超声成像；The medical imaging method is fluorescence imaging, nuclear magnetic imaging, Raman imaging, CT imaging, thermal imaging or ultrasound imaging;
所述的局部注射方式为局部皮下注射、皮内注射、肌肉注射、尾静脉注射或腹腔注射；The local injection method is local subcutaneous injection, intradermal injection, intramuscular injection, tail vein injection or intraperitoneal injection;
裸鼠肿瘤模型为原位移植肿瘤模型、原位转移肿瘤模型、皮下接种肿瘤模型、药物诱导肿瘤模型、基因突变肿瘤模型或自发瘤模型。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.
与现有技术相比，本发明的显著优点是：The significant advantages of the present invention over the prior art are:
（1）本发明制得的银、铂纳米簇粒径小、渗透性好、荧光稳定性高、灵敏度高、靶向性强，可以实现对肿瘤的精确定位；(1) 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;
（2）本发明的银、铂纳米簇通过生物体直接合成，具有很好的生物相容性；(2) The silver and platinum nanoclusters of the present invention are directly synthesized by a living body and have good biocompatibility;
（3）本发明的银、铂纳米簇经超声分散后注射，使纳米颗粒更细更均匀，更有利于吸收；(3) 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;
（4）本发明操作方便、结果直观，可以对肿瘤进行早期检测与诊断，也可以应用在深部肿瘤、大动物等活体肿瘤追踪观察成像等研究中,具有潜在的临床疾病追踪治疗成像的应用价值。(4) 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. .
图1a是本发明实施例1实验组共聚焦荧光显微镜结果图；1a is a diagram showing the results of a confocal fluorescence microscope of an experimental group of Example 1 of the present invention;
图1b是本发明实施例1对照组共聚焦荧光显微镜结果图；Figure 1b is a graph showing the results of a confocal fluorescence microscope of the control group of Example 1 of the present invention;
图2是本发明实施例2裸鼠荧光成像肿瘤靶向成像图。2 is a diagram showing tumor targeting imaging of a nude mouse fluorescent imaging image according to Example 2 of the present invention.
实施例1Example 1
选用肝癌细胞（HepG2）作为研究对象，实验组将处于对数生长期的肝癌细胞（HepG2）按照1.6×105个细胞/孔的密度接种于6孔板中，培养24
h后加入已灭菌并用新鲜无菌的DMEM培养基进行稀释过的含有的谷胱甘肽银氨1 µmol/L溶液。Hepatoma cells (HepG2) 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 μmol/L which had been sterilized and diluted with fresh sterile DMEM medium was added.
对照组将培养基中的肝癌细胞（HepG2）按照1.6×105个细胞/孔的密度接种于6孔板中，培养24
h。培养时间终止后向实验组和对照组的每孔加入磷酸缓冲溶液（PBS,
pH=7.4）冲洗2-3次。然后用共聚焦显微镜进行观察检测。实验组实验结果如图1a所示,对照组实验结果如图1b所示。In the control group, hepatoma cells (HepG2) in the medium were inoculated into a 6-well plate at a density of 1.6×10 5 cells/well, and cultured 24
h. After the incubation time was over, phosphate buffer solution (PBS, was added to each well of the experimental group and the control group.
pH=7.4) Rinse 2-3 times. The observation was then performed using a confocal microscope. 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.
实施例2Example 2
构建裸鼠皮下接种乳腺癌模型，乳腺癌细胞培养24h后加入已灭菌并用新鲜无菌的DMEM
培养基进行稀释过的0.1µ
mol/L的谷胱甘肽银氨溶液，于细胞培养箱中孵育24小时制得银纳米簇，将含有银纳米簇的溶液超声分散后，通过尾静脉注射方法注射到裸鼠体内， 24
h后，对裸鼠进行活体荧光成像。实验表明银纳米簇可对肿瘤部位实现靶向成像。实验结果如图2所示。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 0.1μ
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.
实施例3Example 3
构建裸鼠肝癌原位移植模型，肝癌细胞培养24h后加入已灭菌并用新鲜无菌的DMEM
培养基进行稀释过的50µmol/L的顺式二氨基二络铂溶液，于细胞培养箱中孵育48小时制得铂纳米簇，将含有铂纳米簇的溶液超声分散后，通过局部皮下注射注射到裸鼠体内，24
h后，对裸鼠进行核磁成像并对成像结果进行定性及定量分析。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 μmol/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. In nude mice, 24
After h, the nude mice were subjected to nuclear magnetic imaging and the imaging results were qualitatively and quantitatively analyzed.
实施例4Example 4
构建裸鼠药物诱导卵巢肿瘤模型，卵巢癌细胞培养24
h后加入已灭菌并用新鲜无菌的DMEM培养基进行稀释过的100µmol/L的硝酸银溶液，于细胞培养箱中孵育72小时制得银纳米簇，将含有银纳米簇的溶液超声分散后，通过腹腔注射注射到裸鼠体内，24
h后，对裸鼠进行拉曼成像并对成像结果进行定性及定量分析。Construction of a nude mouse drug-induced ovarian tumor model, ovarian cancer cell culture 24
After h, a 100 μmol/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.
实施例5Example 5
构建裸鼠皮下接种乳腺癌模型，向裸鼠体内通过尾静脉注射方法直接注射0.1µmol/L的银氨溶液，24
h后，对裸鼠进行CT成像并对成像结果进行定性及定量分析。A nude mouse model of subcutaneously inoculated breast cancer was constructed, and a 0.1 μmol/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.
实施例6Example 6
构建裸鼠肝癌原位移植模型，向裸鼠体内通过皮内注射方法直接注射50µ
mol/L的反式二氨基二络铂溶液，24 h后，对裸鼠进行热成像并对成像结果进行定性及定量分析。Construction of a nude mouse orthotopic liver transplantation model, direct injection into the nude mice by intradermal injection of 50μ
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.
实施例7Example 7
构建裸鼠药物诱导卵巢肿瘤模型，向裸鼠体内通过尾静脉注射方法直接注射100µmol/L的谷胱甘肽银溶液，24
h后，对裸鼠进行超声成像并对成像结果进行定性及定量分析。Construction of a nude mouse drug-induced ovarian tumor model, direct injection of 100 μmol/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.
Claims (7)
- 一种银、铂纳米簇在肿瘤靶向成像上的应用，其特征在于：具体步骤为： An application of silver and platinum nanoclusters in tumor targeted imaging is characterized in that: the specific steps are:（1）构建裸鼠肿瘤模型；(1) Constructing a nude mouse tumor model;（2）向裸鼠体内局部注射经超声分散的银或铂纳米簇，或者直接注射0.1-100µmol/L含银溶液或含铂溶液；(2) locally injecting ultrasonically dispersed silver or platinum nanoclusters into nude mice, or directly injecting 0.1-100 μmol/L silver-containing solution or platinum-containing solution;（3）注射24h后，用医学成像方法对裸鼠肿瘤部位进行医学成像并对成像结果进行定性及定量分析。(3) After 24 hours of injection, the tumor sites of nude mice were medically imaged by medical imaging method and the imaging results were qualitatively and quantitatively analyzed.
- 如权利要求1所述的银、铂纳米簇在肿瘤靶向成像上的应用，其特征在于：所述的银或铂纳米簇是通过将含有0.1-100µmol/L含银溶液或含铂溶液的培养液与培养24h的细胞或组织于细胞培养箱中共同孵育24-72小时制得The use of the silver or platinum nanoclusters according to claim 1 for tumor targeted imaging, characterized in that the silver or platinum nanoclusters are obtained by containing a silver-containing solution or a platinum-containing solution of 0.1-100 μmol/L. The culture medium is incubated with the cells or tissues cultured for 24 hours in a cell culture incubator for 24-72 hours.
- 如权利要求1或2所述的银、铂纳米簇在肿瘤靶向成像上的应用，其特征在于：所述的含银溶液为银氨溶液、硝酸银或谷胱甘肽银溶液。The use of silver or platinum nanoclusters according to claim 1 or 2 for tumor targeted imaging, characterized in that the silver-containing solution is a silver ammonia solution, a silver nitrate or a glutathione silver solution.
- 如权利要求1或2所述的银、铂纳米簇在肿瘤靶向成像上的应用，其特征在于：所述的含铂溶液为顺式二氨基二络铂溶液或反式二氨基二络铂溶液。The use of the silver or platinum nanocluster according to claim 1 or 2 for tumor targeted imaging, characterized in that the platinum-containing solution is a cis-diaminodi-platinum solution or a trans-diamino-di-platinum Solution.
- 如权利要求1或2所述的银、铂纳米簇在肿瘤靶向成像上的应用，其特征在于：所述的医学成像方法为荧光成像、核磁成像、拉曼成像、CT成像、热成像或超声成像。The use of silver or platinum nanoclusters according to claim 1 or 2 for tumor targeted imaging, characterized in that the medical imaging method is fluorescence imaging, nuclear magnetic imaging, Raman imaging, CT imaging, thermal imaging or Ultrasound imaging.
- 如权利要求1或2所述的银、铂纳米簇在肿瘤靶向成像上的应用，其特征在于：所述的局部注射方式为局部皮下注射、皮内注射、肌肉注射、尾静脉注射或腹腔注射。The use of silver or platinum nanoclusters according to claim 1 or 2 for tumor targeted imaging, characterized in that the local injection method is local subcutaneous injection, intradermal injection, intramuscular injection, tail vein injection or abdominal cavity. injection.
- 如权利要求1或2所述的银、铂纳米簇在肿瘤靶向成像上的应用，其特征在于：所述的裸鼠肿瘤模型为原位移植肿瘤模型、原位转移肿瘤模型、皮下接种肿瘤模型、药物诱导肿瘤模型、基因突变肿瘤模型或自发瘤模型。 The use of silver or platinum nanoclusters according to claim 1 or 2 for tumor targeted imaging, characterized in that the nude mouse tumor model is an orthotopic transplantation tumor model, an orthotopic metastatic tumor model, and a subcutaneous tumor inoculation. Model, drug-induced tumor model, gene mutation tumor model or spontaneous tumor model.
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| CN105214103B (en) * | 2015-10-14 | 2018-04-24 | 东南大学 | For malignant tumour and the metal ion reagent and image preparation of the quick detection of cardiovascular and cerebrovascular relevant disease early stage and multi-modality imaging |
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