CN108409796B - Application of near-infrared luminescent ruthenium complex in normal mouse organ imaging - Google Patents
Application of near-infrared luminescent ruthenium complex in normal mouse organ imaging Download PDFInfo
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- CN108409796B CN108409796B CN201810189360.9A CN201810189360A CN108409796B CN 108409796 B CN108409796 B CN 108409796B CN 201810189360 A CN201810189360 A CN 201810189360A CN 108409796 B CN108409796 B CN 108409796B
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- 239000012327 Ruthenium complex Substances 0.000 title claims abstract description 23
- 238000003384 imaging method Methods 0.000 title claims abstract description 12
- 210000000056 organ Anatomy 0.000 title abstract description 4
- 210000003734 kidney Anatomy 0.000 claims abstract description 6
- 210000004185 liver Anatomy 0.000 claims abstract description 6
- 241000699670 Mus sp. Species 0.000 claims description 7
- 229910001914 chlorine tetroxide Inorganic materials 0.000 claims description 4
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 4
- 150000001768 cations Chemical class 0.000 claims description 3
- 238000003745 diagnosis Methods 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 238000004020 luminiscence type Methods 0.000 abstract description 7
- 230000005284 excitation Effects 0.000 abstract description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 238000011503 in vivo imaging Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 238000012984 biological imaging Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 206010034972 Photosensitivity reaction Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 230000005283 ground state Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 210000002414 leg Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000001139 pH measurement Methods 0.000 description 1
- 208000007578 phototoxic dermatitis Diseases 0.000 description 1
- 231100000018 phototoxicity Toxicity 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- YAYGSLOSTXKUBW-UHFFFAOYSA-N ruthenium(2+) Chemical compound [Ru+2] YAYGSLOSTXKUBW-UHFFFAOYSA-N 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0046—Ruthenium compounds
- C07F15/0053—Ruthenium compounds without a metal-carbon linkage
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0062—Arrangements for scanning
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2503/00—Evaluating a particular growth phase or type of persons or animals
- A61B2503/40—Animals
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/18—Metal complexes
- C09K2211/185—Metal complexes of the platinum group, i.e. Os, Ir, Pt, Ru, Rh or Pd
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- Surgery (AREA)
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- Radiology & Medical Imaging (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
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- Molecular Biology (AREA)
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Materials Engineering (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
The invention discloses an application of a near-infrared light-emitting binuclear ruthenium complex in normal mouse organ phosphorescence imaging. The binuclear ruthenium complex can image liver and kidney organs in a normal mouse body by detecting luminescence at 710nm under the excitation of visible light with the wavelength of 500 nm.
Description
Technical Field
The invention belongs to the field of optical in-vivo imaging of small animals, and particularly relates to application of a near-infrared light-emitting dual-core ruthenium complex in normal mouse organ imaging.
Background
Near Infrared (NIR) fluorescence/phosphorescence emission (700-; cheng, j.; ma, x.; zhou, x.; chruma, J.J.near-infraredphosphorescences: materials and applications, chem.Soc.Rev.,2013,42,6128. The visible light biological imaging technology has the problems of limited background fluorescence intensity, photobleaching, phototoxicity, tissue penetrability and the like, thereby limiting the application of the visible light biological imaging technology in the fields of chemical biology, clinical examination and diagnosis and the like. The NIR fluorescence/phosphorescence imaging can overcome the defects of the visible light imaging because the NIR luminescent region of endogenous molecules such as hemoglobin and lipid in the wavelength range of 650-900nm has low photon absorption rate and the living tissue has low autofluorescence in the wavelength region, has the advantages of low background interference, small damage to cells, strong sample penetrability, high detection sensitivity and the like, can penetrate through unprecedented deep tissues and obtain signals with high signal to noise ratio in vivo imaging, and has become a biological imaging research hotspot [ Guo, Z.Q.; park, s.; yoon, j.y.; shin, I.Recent progress in the depth of near-dependent fluorescent probes for biological applications, chem.Soc.Rev.,2014,43, 16; escobedo, j.o.; rusin, o.; lim, s.; strongin, r.m.nir Dyes for Bioimaging Applications, curr.opin.chem.biol.,2010,14,64 ]. The ruthenium (II) polypyridine complex has the advantages of highly adjustable ground state and excited state properties, large Stokes shift, excellent thermodynamic/kinetic stability, good water solubility and the like, and is a luminescent material with excellent performance [ Fan, S.H.; zhang, a.g.; ju, c.c.; gao, l.h.; wang, K.Z.Atriphenylamine-grafted imide [4,5-f ] [1,10] phenylanthroline ruthenaum (II) complex: Acid-base and photoelecric Properties, Inorg.Chem.,2010,49,3752], but applications mainly based on visible light emission and in vivo imaging are rarely reported. In the first two patents [ Wangczhi, manting, Zhengzhebao, near infrared light-emitting ruthenium complex pH sensor, patent No.: ZL 201510434319. X; wangchuo, manting, Liu jin, the application of near infrared luminescence ruthenium complex in cell pH sensing, patent application number: 201710332243.9], respectively discloses the near infrared luminescence sensing property of a binuclear ruthenium complex and the application of the binuclear ruthenium complex in the determination of the pH value of HeLa cells. The patent discloses an application of a binuclear ruthenium complex in living body imaging of mice.
Disclosure of Invention
The invention aims to disclose application of a binuclear ruthenium complex in living body imaging of mice.
The technical scheme of the invention is as follows:
the binuclear ruthenium complex used in this experiment was [ (bpy)2Ru(HL1)Ru(H2L2)](ClO4)4The cation complex has the structural formula shown in the following figure:
[(bpy)2Ru(HL1)Ru(H2L2)](ClO4)4according to our published patent methods [ Wangczhi, Bengting, Zhengzhebao, near infrared luminescent ruthenium complex pH sensor, patent application No.: 201510434319.X]And (4) synthesizing. Compared with the existing ruthenium complex living body imaging ruthenium complex, the sensor has the beneficial effects that:
the device can detect the low-energy near infrared region luminescence through visible light excitation, effectively reduce the interference of biological tissue self luminescence, and avoid false positive results.
Drawings
FIG. 1 shows the luminescence of each internal organ of a binuclear ruthenium complex staying in a mouse body for different time periods
Detailed Description
Example 1: near-infrared light-emitting imaging of binuclear ruthenium complex in liver and kidney organs of mouse
The mouse experiments followed the guidelines of the animal experimental administration committee. Prior to the experiment, normal ICR mice, four to five weeks, were acclimated to the animal facility for at least three days and maintained in a thermostated environment at 22 ℃ to provide adequate food and water. Near infrared luminescence in vivo imaging was performed on the IVIS luminea III system in vivo imaging system manufactured by PerkinElmer, usa. The detector was Andor DU897EMCCD, image processing and quantitative analysis were done by professional Kodak molecular imaging software. Mice were dosed with 0.1-10mg/mL dinuclear ruthenium complex DMSO-normal saline (v/v,1:10) solution via tail vein, 100 μ L dinuclear ruthenium complex solution/mouse per injection, and mice were sacrificed after different times of dosing. The administration mouse and a blank control mouse are dissected, and the brain, lung, heart, liver, spleen, kidney, leg muscle, stomach and intestine are imaged in vivo, the excitation wavelength is 500nm, the emission wavelength is 710nm, and a rainbow mode is selected for photographing, and the result is shown in figure 1. From the results in FIG. 1, it is clear that the binuclear ruthenium complex is taken up in the liver and kidney. The results show that the NIR luminous intensity of the disclosed binuclear ruthenium complex can be used for liver and kidney organ imaging in mice.
Claims (1)
1. The use of a dinuclear ruthenium complex in imaging of liver and kidney organs in normal mice for the purpose of non-disease diagnosis, the dinuclear ruthenium complex being [ (bpy)2Ru(HL1)Ru(H2L2)](ClO4)4Consisting of a cation [ (bpy)2Ru(HL1)Ru(H2L2)]4+And an anion ClO4 -A composition characterized in that the cation has the formula:
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CN112565619A (en) * | 2020-11-12 | 2021-03-26 | 上海龙旗科技股份有限公司 | Rainbow photographing method and equipment |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105294770A (en) * | 2015-07-23 | 2016-02-03 | 北京师范大学 | pH sensor made of near-infrared light-emitting Ru complex |
CN105669049A (en) * | 2015-12-31 | 2016-06-15 | 北京师范大学 | Dinuclear ruthenium complex and graphene oxide composite thin film |
CN107118235A (en) * | 2017-05-12 | 2017-09-01 | 北京师范大学 | Application of the near-infrared luminous ruthenium complex in cellular pH sensing |
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Publication number | Priority date | Publication date | Assignee | Title |
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CN105294770A (en) * | 2015-07-23 | 2016-02-03 | 北京师范大学 | pH sensor made of near-infrared light-emitting Ru complex |
CN105669049A (en) * | 2015-12-31 | 2016-06-15 | 北京师范大学 | Dinuclear ruthenium complex and graphene oxide composite thin film |
CN107118235A (en) * | 2017-05-12 | 2017-09-01 | 北京师范大学 | Application of the near-infrared luminous ruthenium complex in cellular pH sensing |
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