CN110025794B - Application of metal iridium complex in preparation of medical long-phosphorescence imaging reagent or medicine - Google Patents

Application of metal iridium complex in preparation of medical long-phosphorescence imaging reagent or medicine Download PDF

Info

Publication number
CN110025794B
CN110025794B CN201910377897.2A CN201910377897A CN110025794B CN 110025794 B CN110025794 B CN 110025794B CN 201910377897 A CN201910377897 A CN 201910377897A CN 110025794 B CN110025794 B CN 110025794B
Authority
CN
China
Prior art keywords
iridium complex
metal iridium
complex
imaging
phosphorescence
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201910377897.2A
Other languages
Chinese (zh)
Other versions
CN110025794A (en
Inventor
杨红
侯雨桐
王晨晨
杨仕平
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shanghai Normal University
Original Assignee
Shanghai Normal University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shanghai Normal University filed Critical Shanghai Normal University
Priority to CN201910377897.2A priority Critical patent/CN110025794B/en
Publication of CN110025794A publication Critical patent/CN110025794A/en
Application granted granted Critical
Publication of CN110025794B publication Critical patent/CN110025794B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

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
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0015—Phosphorescence
    • 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
    • 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

Abstract

The invention discloses application of a metal iridium complex in preparing a medical long-phosphorescence imaging reagent or a medicine, wherein the metal iridium complex takes 2-phenylpyridine as a C ^ N ligand, takes phenanthroline, 3, 8-dibromo phenanthroline or thiophene as an N ^ N ligand, and generates a long-phosphorescence afterglow imaging signal under the condition of no excitation light after being excited by external laser. The invention realizes the medical optical imaging application of the metal iridium complex with high background noise ratio by the optical imaging of the metal iridium complex without real-time excitation in solution and living bodies.

Description

Application of metal iridium complex in preparation of medical long-phosphorescence imaging reagent or medicine
Technical Field
The invention relates to the field of metal complex nano materials and molecular imaging, in particular to application of a metal iridium complex in preparing a medical long-phosphorescence imaging reagent or a medicine.
Background
The diagnosis of optical imaging biomedical images has been widely used. However, since real-time excitation of light is required to generate tissue autofluorescence during imaging, the sensitivity and specificity of in vivo optical imaging are severely affected. Afterglow (Afterglow) or Persistent Luminescence (Persistent Luminescence) is a new focus of attention in the field of optical imaging because it has the ability to emit light continuously after the light source is removed and to achieve zero background imaging in vivo without real-time excitation. Theoretically, the light emission of the afterglow material can be derived from the thermal excitation recombination of holes and electrons in the energy trap or from a long-life excited state at normal temperature, but the light emission life of the organic light emitting material is usually short due to the high-activity excited state. Inorganic metals (e.g. Ir)3+、Pt2+) The complex can enhance the transition conversion from a singlet state to a triplet state in an organic molecule and prolong the light emitting time of the organic molecule by generating energy defects. The metal complex reported at present usually needs to be in a solid crystal shape in a nitrogen atmosphereRealizing long phosphorescence at a state and an ultralow temperature and having application limitation.
Disclosure of Invention
The invention aims to provide application of a metal iridium complex in preparing a medical long-phosphorescence imaging reagent or a medicine, wherein the metal iridium complex takes 2-phenylpyridine as a C ^ N ligand, takes phenanthroline, 3, 8-dibromo phenanthroline or thiophene as an N ^ N ligand, generates a long-phosphorescence afterglow imaging signal in a solution or a living body under the condition of no exciting light after being excited by external laser, and is used for medical imaging detection.
In order to achieve the purpose, the invention adopts the following technical scheme:
the application of the metal iridium complex in preparing a medical long-phosphorescence imaging reagent or a medicine comprises the steps of taking 2-phenylpyridine as a C ^ N ligand and taking phenanthroline, 3, 8-dibromo phenanthroline or thiophene as an N ^ N ligand.
Further, the metal iridium complex is selected from structural formulas shown as the following formula (I), formula (II) or formula (III):
Figure BDA0002050197840000021
further, after being excited by external laser, the metal iridium complex generates a long phosphorescent afterglow imaging signal under the condition of no excitation light.
Further, the metal iridium complex generates a long phosphorescent afterglow imaging signal in a solution, and the intensity of the long phosphorescent afterglow imaging signal is in a linear relation with the solution.
Further, the method for generating long phosphorescent afterglow imaging by the metal iridium complex in the solution comprises the following steps:
the metal iridium complex is protected from light in advance and prepared into 0.1-5 mM acetonitrile or methanol solution, and the optical signal intensity of the solution is collected under the condition of no exciting light and is used as a background signal value;
(ii) irradiating the iridium complex solution in the step (i) with external excitation light for 1-2 min;
(iii) after stopping irradiating for 10-60 s, collecting the optical signal intensity under the condition of no real-time exciting light, wherein the collection interval time is 5-30 s, and the collection duration time is 0.5-10 min.
Further, in the step (i), the iridium complex solution is a 1mM acetonitrile solution, and/or
In step (ii), the external light is an ultraviolet lamp, the excitation wavelength is 365nm, and/or
In step (iii), the collection time is 2 min.
Further, the metal iridium complex generates a long phosphorescent afterglow imaging signal in a living body.
Furthermore, the metal iridium complex is prepared into water-soluble nanoparticles with the concentration of 0.1-0.5 mg/mL, and the usage amount is 30-60 mu L.
Furthermore, the preparation method of the water-soluble nano-particle comprises the following steps: adding 10mg of F127 into 3mL of water, dissolving by ultrasonic, adding 1mg of the metal iridium complex, and performing ultrasonic treatment for 10min by a cell crusher under the power of 20% and then passing through a 0.22 mu m water-soluble filter membrane to obtain the iridium complex.
Further, the medical long-phosphorescence imaging reagent or the medicine takes the metal iridium complex as an active ingredient, or further comprises a pharmaceutically acceptable carrier.
In the technical scheme of the invention, in the ultraviolet-visible absorption spectrum, the charge transfer between metal-ligand in the metal iridium complex solution is (1MLCT) is concentrated at 350-450 nm, an ultraviolet lamp with the wavelength of 365nm is used as an excitation light source for irradiating for 1-2 min, after irradiation is stopped for 30s, the optical signal intensity is collected under the condition of no excitation light, and the collection time is 2 min. Compared with the original solution before excitation, the intensity of the metal iridium complex solution is obviously enhanced, which indicates that the metal iridium complex solution generates afterglow phosphorescence through excitation. In addition, the intensity of the optical signal is enhanced after the light source is removed, possibly because the emitted energy generated during the excitation process is stored and the light energy is released continuously after the light source is removed. By continuously acquiring the optical signal intensity within 10min every 30s, the optical signal intensity of the metallic iridium complex is found to be attenuated along with the time, and the slow energy is further illustratedRelease occurs.
Compared with the prior art, the invention has the beneficial effects that:
1. according to the invention, by designing the metal iridium complex with the same C ^ N ligand and different N ^ N ligands, and removing an excitation light source after excitation for a period of time, the metal iridium complex can still emit light, so that the metal iridium complex has the properties of storing energy and slowly releasing energy after excitation, realizes background-free optical imaging without excitation light, changes the mode that the original iridium complex can only realize optical imaging through real-time excitation, expands the application of the iridium complex in long phosphorescence, and has wide application prospect in the field of molecular imaging.
2. According to the invention, the metal iridium complex with 3, 8-dibromo-phenanthroline as the N ^ N ligand is prepared into the water-soluble nanoparticles, and by utilizing the long-phosphorescence imaging property of the metal iridium complex, background-free optical imaging without real-time exciting light is realized on the back of a mouse, so that the signal-to-noise ratio of the metal iridium complex in optical imaging application is improved, and the application of the metal iridium complex in living body optical imaging is also improved.
Drawings
FIG. 1 is a graph showing the comparison of signal intensity and intensity of 1mM acetonitrile solution of three iridium complexes before and after irradiation for 1min by an ultraviolet lamp.
FIG. 2 shows that the signal intensity of three complex acetonitrile solutions of 1mM and three complex methanol solutions of 5mM are collected every 30s for 8min after the light source is removed and before the irradiation of the ultraviolet lamp and the irradiation of the ultraviolet lamp for 1 min.
FIG. 3 shows acetonitrile solutions of 0.067mM, 0.1mM, 0.2mM, 0.5mM, and 1mM iridium (II) complex, which were excited by a 365nm ultraviolet lamp for 1min, then the light source was removed, and the signal intensity of the solution was collected in the non-excitation mode for 2 min.
FIG. 4 shows acetonitrile solutions of 0.05mg/mL and 0.1mg/mL of iridium (II) complex nanoparticles and iridium (II) complex with the same concentration, which are irradiated by an ultraviolet lamp for 1min, and after the light source is removed, the signal intensity of the solution within 2min is collected in a non-excitation light mode. The preparation process of the nano-particles is as follows: 10mg of F127 was added to 3mL of water, dissolved by sonication, and 1mg of iridium (II) complex was added. At 20% power, sonicate for 10 minutes with a cell disruptor and pass through a 0.22 μm water-soluble filter.
FIG. 5 shows long phosphorescence Images of Iridium (II) complex nanoparticles on the backs of mice, which were anesthetized and then subcutaneously injected with iridium (II) complex nanoparticles (0.2mg/mL, 50 μ L) at specific sites on the backs of mice. After injection, the back of the mice was imaged by irradiating with an ultraviolet lamp for 2min, followed by removing the light source.
Detailed Description
The invention will now be further illustrated by reference to the following examples:
example 1
In this example, 1mM acetonitrile solutions of the three complexes were prepared separately and stored more than one week in the dark. The initial optical signal value is collected under the condition of no exciting light. And then, irradiating for 1min by using an ultraviolet lamp, removing a light source, and continuously collecting the irradiated optical signal value under the condition without exciting light. The quantitative analysis shows that the signal values of the complex (I) solution before and after irradiation are respectively 0.459 multiplied by 105、1.333×105p/sec/cm2/sr, initial 2.9 times after irradiation; the signal values of the complex (III) solution before and after irradiation are 0.6592X 10 respectively5、2.278×105p/sec/cm2/sr, which became 3.5 times the original after irradiation; the signal values of the complex (II) solution before and after irradiation are 0.5172X 10 respectively5、5.413×105p/sec/cm2The signal value of the complex 2 is increased by 3-4 times as much as that of the other two compounds, as shown in figure 1.
Example 2
In this example, a 5mM solution of three complex in methanol was tested, with the light source removed after 1min of UV excitation, with signal value changes every 30 s. As shown in FIG. 2, the signal values of the complex 1, 2 and 3 solutions are 1.34X 10 in sequence5、4.38×105、2.75×105p/sec/cm2The signal value of the complex 2 solution is the highest. The results showed that the signal value of the methanol solution was 0.25X 105p/sec/cm2And/sr, and no significant change over time. The signal values of the three complex solutions are gradually increased along with the timeGradually decreases, and reaches stable and keeps unchanged at 90s, 270s and 120s respectively, and the signal values of the three are close to each other.
Similar tests were carried out in the same way in 1mM acetonitrile, as shown in FIG. 2, and the signal values of the complex 1, 2, 3 solutions were 2.16X 10 in sequence after irradiation with UV light5、4.45×105、2.77×105p/sec/cm2And/sr, the signal values of the three complex solutions gradually decrease along with the time, and reach stability at 90s, 210s and 120s respectively, and the signal values are kept unchanged. And the signal value of the acetonitrile solution is 0.2795 multiplied by 105p/sec/cm2The/sr is hardly changed along with the change of time, and the attenuation process is avoided, thereby indicating that the phosphor property of the three complexes has universality.
Example 3
In this example, as shown in FIG. 3, after the complex (II) acetonitrile solution of 0.067mM, 0.1mM, 0.2mM, 0.5mM, 1mM concentration was irradiated with the ultraviolet lamp for 1min, the phosphorescence intensity was 1.215X 10 in that order5、1.285×105、1.749×105、2.589×105、3.993×105p/sec/cm2And/sr. As the concentration of the material increases, its phosphorescent afterglow intensity also increases. After linear fitting, the relation between the long phosphorescence intensity and the concentration of the complex (II) is that y is 2.9684x +1.0577 (R)20.996), indicating that the phosphorescent afterglow effect is linear with the complex concentration.
Example 4
In this example, the iridium (II) complex is prepared as a nanoparticle by the following procedure: 10mg of F127 was added to 3mL of water, and dissolved by sonication, 1mg of iridium (II) complex was added, and the mixture was sonicated in a cell disruptor at 20% power for 10 minutes and then passed through a 0.22 μm water-soluble filter.
As shown in FIG. 4, by comparing 0.05mg/mL and 0.1mg/mL of acetonitrile solutions of iridium (II) complex nanoparticles and iridium (II) complex, it was found that the phosphorescence signal values of the 0.05mg/mL solution and nanoparticles were 1.974X 10, respectively5p/sec/cm2/sr、4.907×105p/sec/cm2The signal value of the nano particles is about 2.5 times that of the solution; while 0.1mg/mL of the solution and nanoparticles,the phosphor signal values are respectively 2.2 × 105p/sec/cm2/sr、5.935×105p/sec/cm2The ratio of/sr; the signal value of the nanoparticles is about 2.7 times that of the solution, and the iridium (II) complex nanoparticles can enhance the phosphorescence signal intensity of the solution under different concentrations.
Example 5
In this example, a nude mouse was used as a model, and 0.2mg/mL of 50. mu.L of iridium (II) complex nanoparticles was injected subcutaneously into the back, irradiated with an ultraviolet lamp 1cm above it for 1min, followed by removal of the light source, and signal values were collected from the back in the non-excitation light mode, while signal intensity from the back was also collected by fluorescence imaging. As shown in FIG. 5, the long phosphorescence image compared with the fluorescence image clearly shows the back injected material position, the position is clearly compared with other muscle parts, the image is clear, and the intensity ratio of the signal to the muscle area is high (1.47 +/-0.31). In fluorescence imaging, other areas on the back of the mouse have strong background fluorescence, so that the signal of the injected material areas is not obvious, and the signal-to-noise ratio is low (0.14 +/-0.05). From numerical comparison, the signal-to-noise ratio of long phosphorescence imaging is about 10.5 times of that of fluorescence imaging, and it is fully proved that the ratio of the signal of the iridium complex nano-particle in-vivo imaging to muscle tissue can be greatly improved by adopting an afterglow imaging mode without real-time excitation.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention, and the present invention should not be limited by the disclosure of the preferred embodiments. Therefore, it is intended that all equivalents and modifications which do not depart from the spirit of the invention disclosed herein are deemed to be within the scope of the invention.

Claims (1)

1. Use of a metal iridium complex selected from the structural formulae shown in the following formula (ii) for the preparation of a medical long phosphorescence imaging agent:
Figure DEST_PATH_IMAGE002
(Ⅱ)
the metal iridium complex is configured into water-soluble nanoparticles with the concentration of 0.1-0.5 mg/mL, and after external laser excitation, a long phosphorescent afterglow imaging signal is generated in a living body under the condition of no excitation light, the usage amount of the water-soluble nanoparticles is 30-60 mu L, and the configuration method is as follows: adding 10mg of F127 into 3mL of water for ultrasonic dissolution, adding 1mg of the metal iridium complex, performing ultrasonic treatment for 10min by using a cell crusher under the power of 20%, and filtering through a 0.22 mu m water-soluble filter membrane.
CN201910377897.2A 2019-05-06 2019-05-06 Application of metal iridium complex in preparation of medical long-phosphorescence imaging reagent or medicine Active CN110025794B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910377897.2A CN110025794B (en) 2019-05-06 2019-05-06 Application of metal iridium complex in preparation of medical long-phosphorescence imaging reagent or medicine

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910377897.2A CN110025794B (en) 2019-05-06 2019-05-06 Application of metal iridium complex in preparation of medical long-phosphorescence imaging reagent or medicine

Publications (2)

Publication Number Publication Date
CN110025794A CN110025794A (en) 2019-07-19
CN110025794B true CN110025794B (en) 2021-12-03

Family

ID=67241437

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910377897.2A Active CN110025794B (en) 2019-05-06 2019-05-06 Application of metal iridium complex in preparation of medical long-phosphorescence imaging reagent or medicine

Country Status (1)

Country Link
CN (1) CN110025794B (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009067603A1 (en) * 2007-11-21 2009-05-28 Bio-Rad Laboratories, Inc. Photoluminescent metal complexes for protein staining
CN103881700A (en) * 2014-03-14 2014-06-25 上海师范大学 Thienyl phosphorescent iridium complex as well as preparation method and application thereof
CN103936794A (en) * 2014-03-18 2014-07-23 上海师范大学 Water-soluble cationic phosphorescent iridium complex, preparation method and application thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009067603A1 (en) * 2007-11-21 2009-05-28 Bio-Rad Laboratories, Inc. Photoluminescent metal complexes for protein staining
CN103881700A (en) * 2014-03-14 2014-06-25 上海师范大学 Thienyl phosphorescent iridium complex as well as preparation method and application thereof
CN103936794A (en) * 2014-03-18 2014-07-23 上海师范大学 Water-soluble cationic phosphorescent iridium complex, preparation method and application thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
"Membrane Localized Iridium(III) Complex Induces Endoplasmic Reticulum Stress and Mitochondria-Mediated Apoptosis in Human Cancer Cells";Rui Cao 等;《J. Med. Chem》;20130417;第56卷;摘要，以及"EXPERIMENTAL SECTION"部分 *
Rui Cao 等."Membrane Localized Iridium(III) Complex Induces Endoplasmic Reticulum Stress and Mitochondria-Mediated Apoptosis in Human Cancer Cells".《J. Med. Chem》.2013,第56卷摘要，以及"EXPERIMENTAL SECTION"部分. *

Also Published As

Publication number Publication date
CN110025794A (en) 2019-07-19

Similar Documents

Publication Publication Date Title
Askes et al. Solving the oxygen sensitivity of sensitized photon upconversion in life science applications
US20220001032A1 (en) Coated up-conversion nanoparticles
Zhu et al. Anti-Stokes shift luminescent materials for bio-applications
Ford Photochemical delivery of nitric oxide
Sun et al. Nitrogen-doped graphene quantum dots coupled with photosensitizers for one-/two-photon activated photodynamic therapy based on a FRET mechanism
Mapukata et al. Asymmetrical and symmetrical zinc phthalocyanine-cobalt ferrite conjugates embedded in electrospun fibers for dual photocatalytic degradation of azo dyes: Methyl Orange and Orange G
Sardar et al. Direct observation of key photoinduced dynamics in a potential nano-delivery vehicle of cancer drugs
Lemercier et al. Two-photon absorption properties of 1, 10-phenanthroline-based Ru (II) complexes and related functionalized nanoparticles for potential application in two-photon excitation photodynamic therapy and optical power limiting
Ricciardi et al. Plasmon-mediated cancer phototherapy: the combined effect of thermal and photodynamic processes
Matshitse et al. Photophysical properties and photodynamic therapy activities of detonated nanodiamonds-BODIPY-phthalocyanines nanoassemblies
US9757357B2 (en) Photodynamic therapy or diagnostic agent, using infrared-spectrum light
CN109592664B (en) Carbon nanodot with light excitation active oxygen generation performance and preparation method thereof
Sitharaman et al. Time-resolved red luminescence from europium-catalyzed single walled carbon nanotubes
Konar et al. Selective and sensitive detection of cinnamaldehyde by nitrogen and sulphur co-doped carbon dots: a detailed systematic study
Zugle et al. Photophysical and photochemical behavior of electrospun fibers of a polyurethane polymer chemically linked to lutetium carboxyphenoxy phthalocyanine
JP2014519361A (en) Time-gated fluorescence imaging using Si-containing particles
CN110025794B (en) Application of metal iridium complex in preparation of medical long-phosphorescence imaging reagent or medicine
CN111569068B (en) Organic-inorganic hybrid photosensitizer and preparation method of hybrid nano diagnosis and treatment reagent
CN110616071B (en) Red light doped graphene quantum dot and preparation method thereof
Tombe et al. The photophysical and photochemical behaviour of coumarin-derivatized zinc phthalocyanine when conjugated with gold nanoparticles and electrospun into polymer fibers
Kotel’nikov et al. Spectral properties and photodynamic activity of complexes of polycationic derivative of fullerene C60 with xanthene dye fluorescein
Tebello et al. BODIPY dye embedded electrospun polystyrene nanofibers for the photocatalytic degradation of orange G in industrial wastewaters
Kaur et al. Achieving photostability in dye-sensitized upconverting nanoparticles and their use in Fenton type photocatalysis
RU2329061C1 (en) Nanocomposite photosensitiser for method of photodynamic cell effect
JP2021115518A (en) photocatalyst

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant