CN107759533B - Near-infrared fluorescent small molecular probe - Google Patents
Near-infrared fluorescent small molecular probe Download PDFInfo
- Publication number
- CN107759533B CN107759533B CN201711172363.3A CN201711172363A CN107759533B CN 107759533 B CN107759533 B CN 107759533B CN 201711172363 A CN201711172363 A CN 201711172363A CN 107759533 B CN107759533 B CN 107759533B
- Authority
- CN
- China
- Prior art keywords
- imaging
- small molecular
- infrared
- molecular probe
- myelin sheath
- 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
Links
- 239000003068 molecular probe Substances 0.000 title claims abstract description 23
- 210000003007 myelin sheath Anatomy 0.000 claims abstract description 22
- 238000003384 imaging method Methods 0.000 claims abstract description 19
- 239000000523 sample Substances 0.000 claims description 5
- 150000003384 small molecules Chemical class 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 9
- 201000006417 multiple sclerosis Diseases 0.000 abstract description 7
- 238000003333 near-infrared imaging Methods 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 5
- 208000015114 central nervous system disease Diseases 0.000 abstract description 4
- 238000003745 diagnosis Methods 0.000 abstract description 4
- 238000011156 evaluation Methods 0.000 abstract description 2
- 238000011056 performance test Methods 0.000 abstract description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 102000006386 Myelin Proteins Human genes 0.000 description 7
- 108010083674 Myelin Proteins Proteins 0.000 description 7
- 210000005012 myelin Anatomy 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 230000023105 myelination Effects 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 238000000799 fluorescence microscopy Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 208000016192 Demyelinating disease Diseases 0.000 description 2
- 206010012305 Demyelination Diseases 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- 210000003050 axon Anatomy 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000003376 axonal effect Effects 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 210000000877 corpus callosum Anatomy 0.000 description 1
- 210000001653 corpus striatum Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000012631 diagnostic technique Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000009513 drug distribution Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 210000004884 grey matter Anatomy 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
-
- 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
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0028—Oxazine dyes
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
-
- 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
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
- C09K2211/1033—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom with oxygen
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Materials Engineering (AREA)
- Physics & Mathematics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
Abstract
The invention relates to the field of near-infrared imaging, in particular to a near-infrared fluorescent small molecular probe and application thereof in the field of myelin sheath imaging. The structure of the small molecular probe is shown as the following formula, and through fluorescence performance test, the emission wavelength is larger than 650nm and enters a near infrared region. Meanwhile, the small molecular probe can be effectively combined with a myelin sheath part, obviously enhances the imaging effect of the myelin sheath part, can be applied to myelin sheath imaging under the near infrared condition, and can provide a brand new method for diagnosis and curative effect evaluation of central nervous system diseases such as multiple sclerosis.
Description
Technical Field
The invention relates to the field of near-infrared imaging, in particular to a near-infrared fluorescent small molecular probe and application thereof in the field of myelin sheath imaging.
Background
Fluorescence imaging technology has been widely used in many fields such as tumor diagnosis, biomolecule detection, drug distribution and metabolism due to its advantages of non-invasive, visualization, high spatial and temporal resolution, low cost, safety and rapidity. Some components of the living body (such as melanin, hemoglobin, cytochrome, etc.) have high absorption or scattering in the visible light band, which results in poor tissue penetration of visible light, and in this band, the biological tissue has a certain self-fluorescence interference. In contrast, blood and human tissue absorb and scatter less Near Infrared (NIR) light at 650-900nm, so Near Infrared fluorescence is readily transmitted through biological tissue for in vivo fluorescence imaging. Therefore, the development of near-infrared fluorescent materials with low toxicity, good stability and high fluorescence efficiency has become a hot spot in the development of near-infrared fluorescence imaging technology.
Myelin (Myelin) is a membrane of Myelin that wraps around the axons of nerve cells, and is commonly found in the central nervous system of vertebrates. Myelination (Myelination) refers to the process of Myelination which accelerates the speed of nerve excitation as it propagates along nerve fibers, ensures its directional transmission to avoid information interference, and guides axonal regeneration when some axons are damaged. Demyelination (Demyelination) refers to the breakdown of myelin occurring after myelination, and may cause a variety of central nervous system diseases, the most common of which is Multiple Sclerosis (MS).
In the diagnosis and efficacy assessment of MS, the search for methods to qualitatively or quantitatively visualize myelin sheaths in vivo or in vitro has been a goal of researchers and clinicians efforts. To achieve this goal, it is critical to develop molecular probes that are capable of specifically binding to myelin through the blood brain barrier. In the current MS diagnostic technique, the nuclear magnetic resonance imaging technique is mainly relied on, and the method has the disadvantages of no target specificity, complex operation, high cost, etc.
Disclosure of Invention
The invention aims to develop a near-infrared fluorescent small molecular probe which can be specifically combined with myelin sheath, thereby realizing the visualization imaging of myelin sheath in vivo under the near-infrared condition and providing an intuitive, simple, quick and cheap near-infrared imaging method for the diagnosis and curative effect evaluation of central nervous system diseases such as multiple sclerosis.
A near-infrared fluorescent small molecular probe has the following structure:
wherein R is1、R2Represents hydrogen, alkyl of five carbons (containing five), or-NH-R2The substituent can be positioned at 1 position, 2 position, 3 position or 4 position of the benzene ring; the light-emitting diode is characterized in that the emission wavelengths are all larger than 650nm and fall into a near infrared region;
the application of the near-infrared fluorescent small molecular probe is characterized in that the near-infrared fluorescent small molecular probe can be applied to myelin sheath imaging.
Detailed Description
A near-infrared fluorescent small molecular probe has the following structure:
wherein R is1、R2Represents hydrogen, alkyl of five carbons (containing five), or-NH-R2The substituent can be positioned at 1 position, 2 position, 3 position or 4 position of the benzene ring; it is characterized in that the emission wavelengths are all larger than 650nm and fall into the near infrared region.
Fluorescence property test:
the product was dissolved in Dimethylsulfoxide (DMSO), prepared as a 1mM solution, and the excitation wavelength and emission wavelength thereof were measured using a fluorescence spectrophotometer. The structure and the fluorescence performance of a part of near-infrared fluorescent small molecular probes are shown in the table I, and the results show that the emission wavelengths of the probes are larger than 650nm and are in a near-infrared region.
Structure and fluorescence property of part of near-infrared fluorescent small-molecule probe
The application of the near-infrared fluorescent small molecular probe is characterized in that the near-infrared fluorescent small molecular probe can be applied to myelin sheath imaging.
In vitro staining experiments:
in vitro staining experiments are effective methods for detecting specific binding and staining properties of compounds to myelin. The compound to be dyed is prepared into a 1mM solution by using a dimethyl sulfoxide solvent, then the mouse brain corpus callosum, striatum and spinal cord parts of paraffin sections are respectively dyed in vitro, and after exposure imaging is carried out after 25min, the white matter areas (more abundant myelin sheath distribution) of the three parts are obviously brighter than the gray matter areas (less myelin sheath) after the external dyeing is obviously observed, namely, the tested compound can be specifically combined with the myelin sheath and can be well dyed and imaged. The fluorescence performance test result shows that the structural compound is suitable for myelin sheath targeted imaging under the near infrared condition. And the second table is a structure and in vitro staining imaging picture of part of near infrared fluorescent small molecular probes.
Structure of near-infrared fluorescent small molecular probe in table two parts and in vitro staining imaging chart
Living body near-infrared imaging experiment:
to further confirm that the structural compounds can be used for myelin sheath imaging under near infrared conditions, living body near infrared imaging experiments are carried out. A compound to be detected is prepared into a solution with the concentration of 1mg/mL by using a solvent DMSO/PBS, tail veins of 0.1mg/kg are injected into a mouse, the head of the mouse is scanned by using a near-infrared imager after 15min, the brightness of the brain (more myelinated) of the mouse compared with the surrounding area (less myelinated) can be obviously observed, the compound to be detected can be specifically combined with myelin sheath after entering the brain of the mouse, the imaging of the myelin sheath part is obviously enhanced, and the method is suitable for the imaging of the myelin sheath under the near-infrared condition. Meanwhile, to illustrate that brain enhancement imaging is independent of solvent, we performed a control experiment, which showed that the mouse brain imaged indistinguishable from its surrounding area without the test compound. And the third table is a structure and living body near infrared imaging graph of a part of near infrared fluorescent small molecule probes.
Structure of surface three-part near-infrared fluorescent small molecular probe and living body near-infrared imaging diagram
In conclusion, the emission wavelength of the small molecular probe is larger than 650nm, the small molecular probe enters a near infrared region, and meanwhile, the small molecular probe can be effectively combined with a myelin sheath part and obviously enhances the imaging effect of the myelin sheath part, so that the small molecular probe can be applied to myelin sheath imaging under the near infrared condition. The invention provides a brand new method for diagnosing and evaluating the curative effect of central nervous system diseases such as multiple sclerosis, namely a near infrared myelin imaging technology.
Claims (2)
1. A near-infrared fluorescent small molecular probe has the following structure:
wherein R is1、R2Represents an alkyl group of five carbons or less, -NH-R2The substituent can be positioned at 1 position or 2 position of the benzene ring; it is characterized in that the emission wavelengths are all larger than 650nm and fall into the near infrared region.
2. The use of the near-infrared fluorescent small molecule probe as claimed in claim 1, wherein the near-infrared fluorescent small molecule probe can be used for myelin sheath imaging.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711172363.3A CN107759533B (en) | 2017-11-21 | 2017-11-21 | Near-infrared fluorescent small molecular probe |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711172363.3A CN107759533B (en) | 2017-11-21 | 2017-11-21 | Near-infrared fluorescent small molecular probe |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107759533A CN107759533A (en) | 2018-03-06 |
| CN107759533B true CN107759533B (en) | 2020-01-10 |
Family
ID=61279262
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711172363.3A Active CN107759533B (en) | 2017-11-21 | 2017-11-21 | Near-infrared fluorescent small molecular probe |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107759533B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111072584B (en) * | 2019-12-12 | 2022-06-24 | 南京科技职业学院 | Near-infrared fluorescent small molecule probe and preparation and application thereof |
-
2017
- 2017-11-21 CN CN201711172363.3A patent/CN107759533B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN107759533A (en) | 2018-03-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10940216B2 (en) | Cyclic peptides with enhanced nerve-binding selectively, nanoparticles bound with said cyclic peptides, and use of same for real-time in vivo nerve tissue imaging | |
| Valdes et al. | Optical technologies for intraoperative neurosurgical guidance | |
| Gardner et al. | A general approach to convert hemicyanine dyes into highly optimized photoacoustic scaffolds for analyte sensing | |
| Papkovsky et al. | Imaging of oxygen and hypoxia in cell and tissue samples | |
| Roussakis et al. | Oxygen‐sensing methods in biomedicine from the macroscale to the microscale | |
| Sakadžić et al. | Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue | |
| Stewart et al. | Fluorescence guided surgery | |
| Whitney et al. | Fluorescent peptides highlight peripheral nerves during surgery in mice | |
| Kim et al. | In-vivo optical measurement of neural activity in the brain | |
| JP7146264B2 (en) | Devices and methods for imaging shortwave infrared fluorescence | |
| Frullano et al. | A myelin-specific contrast agent for magnetic resonance imaging of myelination | |
| Zhang et al. | Label-free imaging of hemoglobin degradation and hemosiderin formation in brain tissues with femtosecond pump-probe microscopy | |
| Hong et al. | Multimodality imaging of nitric oxide and nitric oxide synthases | |
| WO2017160643A1 (en) | Device and method for imaging shortwave infrared fluorescence | |
| Polomska et al. | Minimally invasive method for the point-of-care quantification of lymphatic vessel function | |
| Yoshihara et al. | Intracellular and intravascular oxygen sensing of pancreatic tissues based on phosphorescence lifetime imaging microscopy using lipophilic and hydrophilic iridium (III) complexes | |
| CN107759533B (en) | Near-infrared fluorescent small molecular probe | |
| EP2906106A1 (en) | Systems, methods, and apparatus for imaging of diffuse media featuring cross-modality weighting of fluorescent and bioluminescent sources | |
| Tseng et al. | In vivo imaging of endogenous enzyme activities using luminescent 1, 2-dioxetane compounds | |
| Chao et al. | Computing hemodynamic response functions from concurrent spectral fiber-photometry and fMRI data | |
| Dong et al. | Microenvironment-responsive small-molecule probe for pulmonary fibrosis detection | |
| Forti et al. | Non-invasive diffuse optical monitoring of cerebral physiology in an adult swine-model of impact traumatic brain injury | |
| Liu et al. | Functional OCT angiography reveals early retinal neurovascular dysfunction in diabetes with capillary resolution | |
| CN111072584B (en) | Near-infrared fluorescent small molecule probe and preparation and application thereof | |
| Toczylowska et al. | Neurotoxic effects of indocyanine green-cerebellar granule cell culture viability study |
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 | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20210826 Address after: 210038 east section 04f, building C5, Hongfeng Science Park, Nanjing Economic and Technological Development Zone, Jiangsu Province Patentee after: Akso (Nanjing) Biotechnology Co.,Ltd. Address before: No. 188, Xinle Road, Jiangbei new district, Nanjing, Jiangsu Province, 210048 Patentee before: NANJING POLYTECHNIC INSTITUTE |