CN108148012A - The second window of near-infrared transmitting small molecule rare earth coordination compound fluorescent probe and preparation method thereof - Google Patents
The second window of near-infrared transmitting small molecule rare earth coordination compound fluorescent probe and preparation method thereof Download PDFInfo
- Publication number
- CN108148012A CN108148012A CN201810008525.8A CN201810008525A CN108148012A CN 108148012 A CN108148012 A CN 108148012A CN 201810008525 A CN201810008525 A CN 201810008525A CN 108148012 A CN108148012 A CN 108148012A
- Authority
- CN
- China
- Prior art keywords
- dota
- rare earth
- nhs
- coordination compound
- fluorescent probe
- 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.)
- Pending
Links
- 229910052761 rare earth metal Inorganic materials 0.000 title claims abstract description 60
- 239000007850 fluorescent dye Substances 0.000 title claims abstract description 32
- 150000001875 compounds Chemical class 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- -1 small molecule rare earth Chemical class 0.000 title abstract description 35
- 150000002910 rare earth metals Chemical class 0.000 claims abstract description 23
- WDLRUFUQRNWCPK-UHFFFAOYSA-N Tetraxetan Chemical compound OC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1 WDLRUFUQRNWCPK-UHFFFAOYSA-N 0.000 claims abstract description 17
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims abstract description 16
- 239000000523 sample Substances 0.000 claims abstract description 13
- 150000002148 esters Chemical class 0.000 claims abstract description 10
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229960000304 folic acid Drugs 0.000 claims abstract description 8
- 235000019152 folic acid Nutrition 0.000 claims abstract description 8
- 239000011724 folic acid Substances 0.000 claims abstract description 8
- 229910052751 metal Inorganic materials 0.000 claims abstract description 8
- 239000002184 metal Substances 0.000 claims abstract description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 19
- 239000000243 solution Substances 0.000 claims description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 239000007864 aqueous solution Substances 0.000 claims description 13
- 238000004090 dissolution Methods 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 12
- 229910052796 boron Inorganic materials 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 8
- 229910017544 NdCl3 Inorganic materials 0.000 claims description 8
- HDGGAKOVUDZYES-UHFFFAOYSA-K erbium(iii) chloride Chemical compound Cl[Er](Cl)Cl HDGGAKOVUDZYES-UHFFFAOYSA-K 0.000 claims description 6
- ATINCSYRHURBSP-UHFFFAOYSA-K neodymium(iii) chloride Chemical compound Cl[Nd](Cl)Cl ATINCSYRHURBSP-UHFFFAOYSA-K 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- STNZNCWQNMGRIM-UHFFFAOYSA-N 2-benzyl-1,4,7,10-tetrakis-(4-methylphenyl)sulfonyl-1,4,7,10-tetrazacyclododecane Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1CCN(S(=O)(=O)C=2C=CC(C)=CC=2)CC(CC=2C=CC=CC=2)N(S(=O)(=O)C=2C=CC(C)=CC=2)CCN(S(=O)(=O)C=2C=CC(C)=CC=2)CC1 STNZNCWQNMGRIM-UHFFFAOYSA-N 0.000 claims description 5
- 239000003208 petroleum Substances 0.000 claims description 5
- 150000003384 small molecules Chemical class 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 3
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 claims description 2
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 abstract description 14
- 238000007385 chemical modification Methods 0.000 abstract description 6
- 229920000768 polyamine Polymers 0.000 abstract description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 4
- 230000014509 gene expression Effects 0.000 abstract description 4
- 230000028993 immune response Effects 0.000 abstract description 4
- 239000003068 molecular probe Substances 0.000 abstract description 4
- 125000000524 functional group Chemical group 0.000 abstract description 3
- 239000012620 biological material Substances 0.000 abstract description 2
- 239000000427 antigen Substances 0.000 abstract 1
- 108091007433 antigens Proteins 0.000 abstract 1
- 102000036639 antigens Human genes 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 7
- 238000010521 absorption reaction Methods 0.000 description 6
- 238000003384 imaging method Methods 0.000 description 6
- QEFYFXOXNSNQGX-UHFFFAOYSA-N neodymium atom Chemical compound [Nd] QEFYFXOXNSNQGX-UHFFFAOYSA-N 0.000 description 4
- 238000013329 compounding Methods 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 2
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 2
- 108010087230 Sincalide Proteins 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000012742 biochemical analysis Methods 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 238000010609 cell counting kit-8 assay Methods 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 229940126864 fibroblast growth factor Drugs 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 238000002595 magnetic resonance imaging Methods 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 238000012285 ultrasound imaging Methods 0.000 description 2
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 1
- 0 C[C@]([C@@](CC[C@]([C@@](*(C)(C1)CC*2C3)OC1=O)(*1(C4)CC5)[C@@]1(C)OC4=O)*5(CC(O1)=O)C11IC)[C@@]21OC3=O Chemical compound C[C@]([C@@](CC[C@]([C@@](*(C)(C1)CC*2C3)OC1=O)(*1(C4)CC5)[C@@]1(C)OC4=O)*5(CC(O1)=O)C11IC)[C@@]21OC3=O 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- IQUHNCOJRJBMSU-UHFFFAOYSA-N H3HP-DO3A Chemical compound CC(O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1 IQUHNCOJRJBMSU-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 1
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 1
- 102000035824 beta Subunit Follicle Stimulating Hormone Human genes 0.000 description 1
- 108010081485 beta Subunit Follicle Stimulating Hormone Proteins 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 239000002041 carbon nanotube Substances 0.000 description 1
- 229910021393 carbon nanotube Inorganic materials 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005034 decoration Methods 0.000 description 1
- 150000001470 diamides Chemical class 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 231100001252 long-term toxicity Toxicity 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 230000004537 potential cytotoxicity Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/337—Polymers modified by chemical after-treatment with organic compounds containing other elements
-
- 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
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2650/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G2650/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule characterized by the type of post-polymerisation functionalisation
- C08G2650/04—End-capping
-
- 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
-
- 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
- C09K2211/1044—Heterocyclic compounds characterised by ligands containing two nitrogen atoms as heteroatoms
-
- 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
- C09K2211/1074—Heterocyclic compounds characterised by ligands containing more than three nitrogen atoms as heteroatoms
-
- 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
- C09K2211/182—Metal complexes of the rare earth metals, i.e. Sc, Y or lanthanide
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Polymers & Plastics (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Materials Engineering (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
The invention belongs to technical field of biological materials, specially the second window of near-infrared transmitting small molecule rare earth metal complex fluorescence probe and preparation method thereof.Fluorescence probe of the present invention includes DOTA and is coordinated the complex to be formed with rare earth Ln (III) metal, and DOTA NHS esters are coordinated the product that the complex to be formed and Ln DOTA NHS are reacted with amino PEG folic acid with rare earth Ln (III) metal.The present invention achievees the effect that target tumor, while realize the operation excision under infrared window guidance by changing coordination ability of the functional group of Macrocyclic polyamine structure without influencing Macrocyclic polyamine and rare earth ion after being combined with the receptor-specific of tumor surface.According to the donor type to small molecule rare earth coordination compound fluorescent probe chemical modification, molecular probe can specifically target various tumours, realize the immune response of antibody antigen and realize gene expression by the base-pair pairing of DNA sequence dna.
Description
Technical field
The invention belongs to technical field of biological materials, and in particular to a kind of small molecule rare earth coordination compound fluorescent probe and its system
Preparation Method.
Background technology
Molecular image technology such as X-ray common at present, Tomography (CT), magnetic resonance imaging (MRI) and ultrasound
Imaging (US) is as an aid in surgical operation, but these are not tumour-specifics, usually to operation application effect and pays no attention to
Think.The advantages that fluorescence imaging is due to real-time, Noninvasive, required sample size is few, high-resolution, in life science and biotechnology
The fields such as field have been widely used, and the fluorescence imaging mode especially with target tumor specificity should with more certain
With value.In in the past few years, researchers are dedicated to studying the fluoroscopic examination of near-infrared first window (700nm~900nm)
And imaging, but since there are very strong absorption and scattering in biological tissue in this wavelength band, cause its signal-to-noise ratio and tissue
Penetration depth is all than relatively low.Therefore, some recent research work be concentrated mainly on the second window of near-infrared light (1000nm~
1700nm), in this wave band, the absorption and scattering of biological tissue itself are weak, can thus greatly improve image quality and
Penetration depth.At present, some inorganic material such as carbon nanotube, quantum dot, rare-earth nanometer particles and organic dye molecule can be real
The transmitting of existing the second window region of near-infrared, but their emission peak is wider, into live body after be metabolized slow, exist potential
Cytotoxicity, dissolubility is poor in water, and which greatly limits their application values.
Small molecule rare earth metal complex can also realize the transmitting of the second window region of near-infrared, and with Stokes
Displacement is big, sharp line emission spectrum, fluorescence lifetime are long, compared with high luminous efficiency, the advantages such as photobleaching is small, long term toxicity is low, is to use
In a kind of very promising fluorescence probe of deep tissue biopsy imaging.The unique electronic structure of rare earth ion makes it have many spies
Different spectral quality.Rare earth ion is since f-f transition belongs to forbidden transition, and the light absorpting ability of its own is very weak, Molar Extinction
Coefficient very little.Therefore the luminous of them is mainly what is realized by the sensibilization of ligand.Current rare earth compounding is most
Number is the rare earth compounding of the VISIBLE LIGHT EMISSION of UV, visible light photosensitizer.Therefore, there is higher shine under near infrared light excitation
The rare earth compounding of efficiency will be a kind of lower living imaging of ideal deep tissue and the fluorescence of the operation excision under imaging guidance
Probe.By changing the coordination ability of the functional group of macrocyclic structure without influencing Macrocyclic polyamine and rare earth ion, can chemistry repair
It is capable of the donor of target tumor on decorations, target tumor is achieved the effect that after being combined with the receptor-specific of tumor surface, while real
Operation excision under present infrared window guidance.According to the donor class to small molecule rare earth coordination compound fluorescent probe chemical modification
Type, molecular probe can specifically target various tumours, the base realized the immune response of antibody-antigene and pass through DNA
Gene expression is realized to pairing.There is broader practice prospect in terms of clinical biochemical analysis and disease detection.
Invention content
The purpose of the present invention is to provide a kind of preparation process is simple, good water solubility, photostability are high, kidney removing is fast, can
For the small molecule rare earth metal of the operation excision under the deep living imaging for organizing the transmitting of the second window of near-infrared and imaging guidance
Coordination compound fluorescent probe and preparation method thereof.
The small molecule rare earth metal complex fluorescence probe of the second window of near-infrared provided by the invention transmitting, is Isosorbide-5-Nitrae, 7,
10- tetraazacyclododecanands-Isosorbide-5-Nitrae, 7,10- tetraacethyls (DOTA) are coordinated the complex to be formed with rare earth Ln (III) metal, are denoted as
Ln-DOTA, general structure are as follows：
Further, the small molecule rare earth metal complex fluorescence probe of the second window of near-infrared transmitting provided by the invention,
It is that DOTA derivative DOTA-NHS esters are coordinated the complex to be formed with rare earth Ln (III) metal, is denoted as Ln-DOTA-NHS, ties
Structure general formula is as follows：
Further, the small molecule rare earth metal complex fluorescence probe of the second window of near-infrared transmitting provided by the invention,
It is by above-mentioned rare earth coordination compound fluorescent probe Ln-DOTA-NHS and amino PEG folic acid (NH2- PEG-FA) reaction product, note
It, can be as the rare earth coordination compound fluorescent probe of the second window of near-infrared transmitting of targeting oophoroma, structure for Ln-DOTA-FA
General formula is as follows：
In the present invention, rare earth Ln (III) metal is chloride, and chloride is selected from：NdCl3·6H2O, ErCl3·
6H2O, TmCl3·6H2O or HoCl3·6H2O。
The preparation method of small molecule rare earth metal complex fluorescence probe proposed by the present invention, it is specific as follows：
(1) Ln-DOTA small molecule rare earth coordination compound fluorescent probes are prepared.
1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is weighed, is put into single necked round bottom flask,
With the water dissolution of 1~3ml；Then weighing rare earth-iron-boron, (rare earth-iron-boron is selected from NdCl3·6H2O, ErCl3·6H2O,
TmCl3·6H2O, HoCl3·6H2O), with the water dissolution of 1~2ml, aqueous chloride solution is slowly dropped to the water-soluble of DOTA
In liquid, it is stirred at room temperature；PH is adjusted with NaOH solution, makes it between 6.0~6.5；Reaction 12~24 hours stops reaction；It is slow
Slow addition anhydrous ether or petroleum ether are precipitated, and are stood, and are filtered, are obtained corresponding solid powder, be denoted as Ln-DOTA；DOTA
Molar ratio with rare earth-iron-boron is 1:1~1:3, with 1:1 is optimal conditions.
(2) Ln-DOTA-NHS small molecule Nd complex fluorescence probes are prepared.
DOTA derivative DOTA-NHS esters (DOTA-NHS) are weighed to be put into single necked round bottom flask, it is water-soluble with 1~3ml
Solution；Then weighing rare earth-iron-boron, (rare earth-iron-boron is selected from NdCl3·6H2O,ErCl3·6H2O,TmCl3·6H2O,
HoCl3·6H2O), with the water dissolution of 1~2ml, aqueous chloride solution is slowly dropped in the aqueous solution of DOTA-NHS esters, room
Temperature stirring；PH is adjusted with NaOH solution, makes it between 6.0~6.5；Reaction 12~24 hours stops reaction；It is slowly added to nothing
Water ether or petroleum ether are precipitated；It stands, filters, obtain white solid, be denoted as Ln-DOTA-NHS；DOTA-NHS esters with it is dilute
The molar ratio of native chloride is 1:1~1:3, with 1:1 is optimal conditions.
(3) Ln-DOTA-FA small molecule Nd complex fluorescence probes are prepared.
Weigh the solid of step (2) preparation, be put into single necked round bottom flask, add in n,N-diisopropylethylamine (DIPEA) and
N, N- dimethylformamide (DMF), are stirred at room temperature, and then weigh amino PEG folic acid (NH2- PEG-FA), with the water of 1~2ml
Dissolving, is slowly dropped in the solution of Ln-DOTA-NHS, after being stirred at room temperature 12~24 hours, stops reacting, concentration of reaction solution,
With anhydrous ether or petroleum ether for several times, yellow solid is obtained, as required Ln-DOTA-FA small molecules Nd complex fluorescence
Probe.
Wherein, the mass ratio of n,N-diisopropylethylamine and n,N-Dimethylformamide is 1:8~1:10, preferably 1:9.
In the present invention, by taking small molecule rare earth coordination compound fluorescent probe molecule Nd-DOTA as an example, in aqueous solution, in 740nm
And have stronger absorption at 802nm, further with the laser of 808nm excite, be able to observe that rare earth neodymium ion in 1060nm
With the fluorescence emission peak (Fig. 1) at 1330nm.
In the present invention, by taking small molecule rare earth coordination compound fluorescent probe molecule Nd-DOTA as an example, in aqueous solution at 1060nm
Fluorescence lifetime be 5.37 μ s.
In the present invention, by taking small molecule rare earth coordination compound fluorescent probe molecule Nd-DOTA as an example, fluorescence volume in aqueous solution
Sub- yield is 0.3%.
In the present invention, by taking small molecule rare earth coordination compound fluorescent probe molecule Nd-DOTA as an example, in swashing for 808nm lasers
It gives, respectively in aqueous solution, PBS buffer solutions and mouse blood, photostability remains unchanged (Fig. 2) in 2 hours.
In the present invention, by taking small molecule rare earth coordination compound fluorescent probe molecule Nd-DOTA as an example, when concentration is in 500 μ g/ml
When, cell survival rate still more than 95% (Fig. 3).
The present invention is by changing configurational energy of the functional group of Macrocyclic polyamine structure without influencing Macrocyclic polyamine and rare earth ion
Power, can be to be capable of the donor of target tumor in chemical modification, and then reaches targeting after being combined with the receptor-specific of tumor surface
The effect of tumour, while realize the operation excision under infrared window guidance.
According to the donor type to small molecule rare earth coordination compound fluorescent probe chemical modification, molecular probe can be specifically
Various tumours are targeted, realize the immune response of antibody-antigene and gene expression is realized by the base-pair pairing of DNA sequence dna.
There is broader practice prospect in terms of clinical biochemical analysis and disease detection.
It is also applied for being commercialized with the ligand of rare earth metal coordination in the present invention and be made applied to MRI magnetic resonance clinically
Remaining 5 kinds of ligand of shadow agent：The derivative DO3A-butrol and HP-DO3A, DTPA of DOTA and its diamide derivatives DTPA-
BMA and DTPA-BMEA.Their corresponding structural formulas are as follows：
Donor of the present invention for chemical modification targeting includes folic acid (FA), follicular stimulating hormone (FSH β), RGD peptide, matrix
Metalloproteinases (MMP), epidermal growth factor (EGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF)
And some other antibody and DNA sequence dna etc..
In the present invention, for small molecule rare earth coordination compound fluorescent probe according to the donor type of chemical modification, molecular probe can
Various tumours are specifically targeted, realize the immune response of antibody-antigene and base is realized by the base-pair pairing of DNA sequence dna
Because of expression.
Description of the drawings
Fig. 1 is excited for 808nm near-infrareds, the absorption of small molecule rare earth coordination compound fluorescent probe molecule Nd-DOTA and fluorescence
Emit spectrogram.
Fig. 2 is excited for 808nm near-infrareds, and small molecule rare earth coordination compound fluorescent probe molecule Nd-DOTA is in aqueous solution, PBS
Photostability spectrogram in buffer solution and nude mice blood.
Fig. 3 is the cytotoxicity figure of small molecule rare earth coordination compound fluorescent probe molecule Nd-DOTA.
Fig. 4 is the excitation of 808nm near-infrareds, and small molecule rare earth coordination compound fluorescent probe molecule be Nd-DOTA-NHS's and fluorescence
Emit spectrogram.
Fig. 5 is excited for 808nm near-infrareds, and small molecule rare earth coordination compound fluorescent probe molecule Nd-DOTA-FA's sends out with fluorescence
Penetrate spectrogram.
Specific embodiment
Embodiment 1：
The preparation of small molecule rare earth coordination compound fluorescent probe molecule Nd-DOTA.It is as follows：
1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is weighed to be put into single necked round bottom flask,
With the water dissolution of 1~3ml.Then NdCl is weighed3·6H2O, with the water dissolution of 1~2ml, by NdCl3Aqueous solution is slowly dropped to
In the aqueous solution of DOTA, stirring at normal temperature.PH is adjusted with NaOH solution, makes it between 6.0~6.5.After reaction 12~24 hours,
Stop reaction.Anhydrous ether is slowly added to be precipitated.It stands, filters, obtain light purple solid powder.Small molecule rare earth coordinates
Object fluorescent probe molecule Nd-DOTA in aqueous solution, there is stronger absorption at 740nm and 802nm, further with 808nm's
Laser excites, and is able to observe that fluorescence emission peak of the rare earth neodymium ion at 1060nm and 1330nm (referring to Fig. 1).
Embodiment 2：
The preparation of small molecule rare earth coordination compound fluorescent probe molecule Nd-DOTA-NHS.It is as follows：
DOTA derivative DOTA-NHS esters (DOTA-NHS) are weighed to be put into single necked round bottom flask, it is water-soluble with 1~3ml
Solution.Then NdCl is weighed3·6H2O, with the water dissolution of 1~2ml, by NdCl3Aqueous solution is slowly dropped to the water-soluble of DOTA-NHS
In liquid, stirring at normal temperature.PH is adjusted with NaOH solution, makes it between 6.0~6.5.After reaction 12~24 hours, stop reaction.
Anhydrous ether is slowly added to be precipitated.It stands, filters, obtain white solid.Small molecule rare earth coordination compound fluorescent probe molecule
The aqueous solution of Nd-DOTA-NHS is excited with the laser of 808nm, is able to observe that rare earth neodymium ion in transmitting strong 1060nm
Weaker fluorescence emission peak at peak and 1330nm (referring to Fig. 4).
Embodiment 3：
The preparation of small molecule rare earth coordination compound fluorescent probe molecule Nd-DOTA-FA.It is as follows：
The solid for weighing Nd-DOTA-NHS is put into single necked round bottom flask, adds in n,N-diisopropylethylamine (DIPEA) and N,
Then N- dimethylformamides (DMF) (1/9), stirring at normal temperature weigh amino PEG folic acid (NH2- PEG-FA), with 1~2ml's
Water dissolution is slowly dropped in the solution of Nd-DOTA-NHS, and stirring at normal temperature stops reaction, concentration reaction after 12~24 hours
Liquid is washed for several times with anhydrous ether, obtains yellow solid.The water of small molecule rare earth coordination compound fluorescent probe molecule Nd-DOTA-FA
Solution is excited with the laser of 808nm, be able to observe that rare earth neodymium ion at 1060nm strong emission peak and 1330nm compared with
Weak fluorescence emission peak (referring to Fig. 5).
Embodiment 4：
The processing of small molecule rare earth coordination compound fluorescent probe molecule Nd-DOTA cell toxicity tests.Cytotoxicity CCK-8
Reagent is completed, and cell used is CaVO3 cells.It is as follows：
CaVO3 cells (1 × 104) on 96 orifice plates, 5%CO2With 37 DEG C at be cultured 24 hours.Then cell is different
The Nd-DOTA complexs of concentration come be further incubated at identical conditions 24 hours (concentration is followed successively by 0,100,200,300,
400,500μg/mL).The PBS solution of the CCK-8 of 10 μ L is added in most backward each orifice plate, is cultivated 4 hours at 37 DEG C, with enzyme mark
Instrument measures.Measured value is based on the absorption at 450nm.Cell survival rate can be calculated with this following formula：
Cell survival rate (%)=(mean absorbance of mean absorbance/control group of experimental group) × 100.
Claims (3)
1. a kind of rare earth coordination compound fluorescent probe of the second window of near-infrared transmitting, which is characterized in that for Isosorbide-5-Nitrae, 7,10- tetra- azepines
Cyclododecane-Isosorbide-5-Nitrae, 7,10- tetraacethyls (DOTA) are coordinated the complex to be formed with rare earth Ln (III) metal, are denoted as Ln-DOTA,
Its general structure is as follows：
Or the complex to be formed is coordinated with rare earth Ln (III) metal for DOTA derivative DOTA-NHS esters, it is denoted as Ln-DOTA-
NHS, general structure are as follows：
Or the product reacted for the rare earth coordination compound fluorescent probe Ln-DOTA-NHS with amino PEG folic acid, general structure
It is as follows：
2. the rare earth coordination compound fluorescent probe of the second window of near-infrared transmitting according to claim 1, which is characterized in that institute
Rare earth Ln (III) metal is stated as chloride, is selected from：NdCl3·6H2O,ErCl3·6H2O,TmCl3·6H2O,HoCl3·6H2O。
3. a kind of preparation method of the rare earth coordination compound fluorescent probe of second window of near-infrared as described in claim 1 transmitting,
It is characterized in that：
The Ln-DOTA preparations are as follows：
1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is weighed, is put into single necked round bottom flask, with 1
The water dissolution of~3ml；Then rare earth-iron-boron is weighed, rare earth-iron-boron is selected from NdCl3·6H2O, ErCl3·6H2O, TmCl3·
6H2O,HoCl3·6H2O with the water dissolution of 1~2ml, aqueous chloride solution is slowly dropped in the aqueous solution of DOTA, room temperature
Stirring；PH is adjusted with NaOH solution, makes it between 6.0~6.5；After reaction 12~24 hours, stop reaction；It is slowly added to nothing
Water ether or petroleum ether are precipitated, and are stood, and are filtered, are obtained corresponding solid powder, be denoted as Ln-DOTA；Wherein, DOTA with it is dilute
The molar ratio of native chloride is 1:1~1:3；
The preparation of the Ln-DOTA-NHS is as follows：
It weighs DOTA derivative DOTA-NHS esters (DOTA-NHS) to be put into single necked round bottom flask, with the water dissolution of 1~3ml；So
After weigh rare earth-iron-boron, rare earth-iron-boron is selected from NdCl3·6H2O, ErCl3·6H2O, TmCl3·6H2O,HoCl3·6H2O,
With the water dissolution of 1~2ml, aqueous chloride solution is slowly dropped in the aqueous solution of DOTA-NHS esters, be stirred at room temperature；Use NaOH
Solution adjusts pH, makes it between 6.0~6.5；Reaction 12~24 hours stops reaction；It is slowly added to anhydrous ether or oil
Ether is precipitated；It stands, filters, obtain white solid, be denoted as Ln-DOTA-NHS；DOTA-NHS esters and rare earth-iron-boron rub
You are than being 1:1~1:3；
The preparation of the Ln-DOTA-FA is as follows：
It weighs solid Ln-DOTA-NHS and is put into single necked round bottom flask, add in n,N-diisopropylethylamine and N, N- dimethyl formyl
Amine is stirred at room temperature, and then weighs amino PEG folic acid, with the water dissolution of 1~2ml, is slowly dropped to the solution of Ln-DOTA-NHS
In, after being stirred at room temperature 12~24 hours, stop reaction, concentration of reaction solution with anhydrous ether or petroleum ether for several times, obtains Huang
Color solid, as required Ln-DOTA-FA small molecules Nd complex fluorescence probe；Wherein, n,N-diisopropylethylamine and N, N- bis-
The mass ratio of methylformamide is 1:8~1:10.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810008525.8A CN108148012A (en) | 2018-01-04 | 2018-01-04 | The second window of near-infrared transmitting small molecule rare earth coordination compound fluorescent probe and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810008525.8A CN108148012A (en) | 2018-01-04 | 2018-01-04 | The second window of near-infrared transmitting small molecule rare earth coordination compound fluorescent probe and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108148012A true CN108148012A (en) | 2018-06-12 |
Family
ID=62460851
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810008525.8A Pending CN108148012A (en) | 2018-01-04 | 2018-01-04 | The second window of near-infrared transmitting small molecule rare earth coordination compound fluorescent probe and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108148012A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109828107A (en) * | 2019-01-16 | 2019-05-31 | 清华大学 | A kind of polyatom rubidium marking probe and the preparation method and application thereof |
| CN111892645A (en) * | 2020-06-16 | 2020-11-06 | 南方科技大学 | Organic coordination compound, preparation method and application thereof, and probe |
| US11964948B2 (en) | 2022-06-07 | 2024-04-23 | Actinium Pharmaceuticals, Inc. | Bifunctional chelators and conjugates |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998013338A1 (en) * | 1996-09-24 | 1998-04-02 | Schering Aktiengesellschaft | Ion pairs, process for producing the same and their use as contrast agents |
| WO1998048844A2 (en) * | 1997-04-29 | 1998-11-05 | Schering Aktiengesellschaft | Ion paris, method for the production and use thereof as contrast agents |
-
2018
- 2018-01-04 CN CN201810008525.8A patent/CN108148012A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998013338A1 (en) * | 1996-09-24 | 1998-04-02 | Schering Aktiengesellschaft | Ion pairs, process for producing the same and their use as contrast agents |
| WO1998048844A2 (en) * | 1997-04-29 | 1998-11-05 | Schering Aktiengesellschaft | Ion paris, method for the production and use thereof as contrast agents |
Non-Patent Citations (5)
| Title |
|---|
| ANDHIKA KISWANDHI ET AL.: "Impact of Ho3+-doping on 13C dynamic nuclear polarization using trityl OX063 free radical", 《PHYS.CHEM.CHEM.PHYS.》 * |
| EMRIN ZITHA-BOVENS ET AL.: "Interactions Between Cyclodextrins and TmIII Chelates of Polyazamacrocycles as Studied by NMR in Aqueous Solution", 《EUR. J. INORG. CHEM.》 * |
| JUN ZHOU ET AL.: "In vivo evaluation of medical device-associated inflammation using a macrophage-specific positron emission tomography (PET) imaging probe", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
| 仇衍楠等: "近红外发光稀土配合物及杂化材料研究进展", 《中国稀土学报》 * |
| 孙钰林等: "64Cu-DOTA-SPIONs-PEG-FA：靶向叶酸受体阳性肿瘤的PET／MRI双模态显像探针", 《核化学与放射化学》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109828107A (en) * | 2019-01-16 | 2019-05-31 | 清华大学 | A kind of polyatom rubidium marking probe and the preparation method and application thereof |
| CN111892645A (en) * | 2020-06-16 | 2020-11-06 | 南方科技大学 | Organic coordination compound, preparation method and application thereof, and probe |
| CN111892645B (en) * | 2020-06-16 | 2021-12-21 | 南方科技大学 | Organic coordination compound, preparation method and application thereof, and probe |
| US11964948B2 (en) | 2022-06-07 | 2024-04-23 | Actinium Pharmaceuticals, Inc. | Bifunctional chelators and conjugates |
| US11975081B2 (en) | 2022-06-07 | 2024-05-07 | Actinium Pharmaceuticals, Inc. | Bifunctional chelators and conjugates |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Chatterjee et al. | Upconversion fluorescence imaging of cells and small animals using lanthanide doped nanocrystals | |
| Tao et al. | Early tumor detection afforded by in vivo imaging of near-infrared II fluorescence | |
| Yao et al. | Upconversion luminescence nanomaterials: A versatile platform for imaging, sensing, and therapy | |
| Chuang et al. | Photostimulable near-infrared persistent luminescent nanoprobes for ultrasensitive and longitudinal deep-tissue bio-imaging | |
| Wei et al. | Cysteine modified rare-earth up-converting nanoparticles for in vitro and in vivo bioimaging | |
| Yu et al. | Neurotoxin-conjugated upconversion nanoprobes for direct visualization of tumors under near-infrared irradiation | |
| Zako et al. | Cyclic RGD peptide-labeled upconversion nanophosphors for tumor cell-targeted imaging | |
| Zhang et al. | Dual modal in vivo imaging using upconversion luminescence and enhanced computed tomography properties | |
| CN107118765B (en) | A kind of kernel targeting fluorescent carbon point and the preparation method and application thereof | |
| CN108148012A (en) | The second window of near-infrared transmitting small molecule rare earth coordination compound fluorescent probe and preparation method thereof | |
| CN105363043A (en) | RGD-labeled fluorescent gold nano-cluster preparation method | |
| Solhi et al. | Recent advances on the biosensing and bioimaging based on polymer dots as advanced nanomaterial: Analytical approaches | |
| CN109251743A (en) | Hydrogen peroxide response ratiometric nanoprobe and application thereof | |
| He et al. | Recent advances of aggregation-induced emission materials for fluorescence image-guided surgery | |
| Ren et al. | Tb-Doped core–shell–shell nanophosphors for enhanced X-ray induced luminescence and sensitization of radiodynamic therapy | |
| US20120070378A1 (en) | Lanthanide ion complexes and imaging method | |
| CN104830318B (en) | A kind of fluorescent tag molecule of high state of aggregation fluorescent emission and preparation method thereof | |
| CN107058299B (en) | Near-infrared fluorescent nucleic acid silver nanocluster and preparation method and application thereof | |
| CN106983874A (en) | Gold nanorod/polyethylene glycol/carbon dot nano hybrid imaging contrast material and preparation method and application thereof | |
| CN103143037B (en) | Method for synthesizing rare earth metal compound nano cluster and application thereof | |
| CN111999504B (en) | Mucin 1 and sialylglycosyl dual fluorescence imaging method and application thereof | |
| CN109438425A (en) | A kind of near infrared fluorescent dye, preparation method and application | |
| Chen et al. | Bioorthogonal chemistry in metal clusters: a general strategy for the construction of multifunctional probes for bioimaging in living cells and in vivo | |
| CN102940893B (en) | Contrast agent having two functions of up-conversion luminescence and magnetic resonance imaging, and method for preparing same | |
| Cai et al. | Rare earth nanoparticles for sprayed and intravenous NIR II imaging and photodynamic therapy of tongue cancer |
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 |