CN114805293A - D-π-A化合物、含有该化合物的具有近红外二区发光特性的多功能光疗剂 - Google Patents
D-π-A化合物、含有该化合物的具有近红外二区发光特性的多功能光疗剂 Download PDFInfo
- Publication number
- CN114805293A CN114805293A CN202210324354.6A CN202210324354A CN114805293A CN 114805293 A CN114805293 A CN 114805293A CN 202210324354 A CN202210324354 A CN 202210324354A CN 114805293 A CN114805293 A CN 114805293A
- Authority
- CN
- China
- Prior art keywords
- compound
- multifunctional
- infrared
- phototherapy agent
- cho
- 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
- 238000001126 phototherapy Methods 0.000 title claims abstract description 43
- 150000001875 compounds Chemical class 0.000 title claims abstract description 30
- 238000004020 luminiscence type Methods 0.000 title description 5
- 229920000642 polymer Polymers 0.000 claims abstract description 12
- 239000011258 core-shell material Substances 0.000 claims abstract description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 36
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 9
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 7
- 229910052763 palladium Inorganic materials 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 229940126062 Compound A Drugs 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 150000007529 inorganic bases Chemical class 0.000 claims description 6
- 239000002105 nanoparticle Substances 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- 238000006482 condensation reaction Methods 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 235000011181 potassium carbonates Nutrition 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- 239000011261 inert gas Substances 0.000 claims description 3
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 claims description 2
- 101150003085 Pdcl gene Proteins 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 claims description 2
- 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 claims description 2
- 230000009471 action Effects 0.000 claims description 2
- 229920001992 poloxamer 407 Polymers 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 2
- 238000009210 therapy by ultrasound Methods 0.000 claims description 2
- 238000005286 illumination Methods 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 11
- 201000011510 cancer Diseases 0.000 abstract description 7
- 238000011503 in vivo imaging Methods 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000002428 photodynamic therapy Methods 0.000 description 5
- 238000007626 photothermal therapy Methods 0.000 description 5
- ZKSVYBRJSMBDMV-UHFFFAOYSA-N 1,3-diphenyl-2-benzofuran Chemical compound C1=CC=CC=C1C1=C2C=CC=CC2=C(C=2C=CC=CC=2)O1 ZKSVYBRJSMBDMV-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000008367 deionised water Substances 0.000 description 4
- 229910021641 deionized water Inorganic materials 0.000 description 4
- 238000000799 fluorescence microscopy Methods 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 230000002195 synergetic effect Effects 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 230000002147 killing effect Effects 0.000 description 3
- 238000011275 oncology therapy Methods 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- NSGDYZCDUPSTQT-UHFFFAOYSA-N N-[5-bromo-1-[(4-fluorophenyl)methyl]-4-methyl-2-oxopyridin-3-yl]cycloheptanecarboxamide Chemical compound Cc1c(Br)cn(Cc2ccc(F)cc2)c(=O)c1NC(=O)C1CCCCCC1 NSGDYZCDUPSTQT-UHFFFAOYSA-N 0.000 description 2
- 206010034972 Photosensitivity reaction Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- TWWQCBRELPOMER-UHFFFAOYSA-N [4-(n-phenylanilino)phenyl]boronic acid Chemical compound C1=CC(B(O)O)=CC=C1N(C=1C=CC=CC=1)C1=CC=CC=C1 TWWQCBRELPOMER-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000012295 chemical reaction liquid Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000000635 electron micrograph Methods 0.000 description 2
- 238000002189 fluorescence spectrum Methods 0.000 description 2
- 239000003517 fume Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 208000007578 phototoxic dermatitis Diseases 0.000 description 2
- 231100000018 phototoxicity Toxicity 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- UHKAJLSKXBADFT-UHFFFAOYSA-N 1,3-indandione Chemical compound C1=CC=C2C(=O)CC(=O)C2=C1 UHKAJLSKXBADFT-UHFFFAOYSA-N 0.000 description 1
- TUCRZHGAIRVWTI-UHFFFAOYSA-N 2-bromothiophene Chemical compound BrC1=CC=CS1 TUCRZHGAIRVWTI-UHFFFAOYSA-N 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 208000007660 Residual Neoplasm Diseases 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000008832 photodamage Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 230000006950 reactive oxygen species formation Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- ODHXBMXNKOYIBV-UHFFFAOYSA-N triphenylamine Chemical compound C1=CC=CC=C1N(C=1C=CC=CC=1)C1=CC=CC=C1 ODHXBMXNKOYIBV-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
- A61K9/5153—Polyesters, e.g. poly(lactide-co-glycolide)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/18—[b, e]-condensed with two six-membered rings
- C07D279/22—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- 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
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1003—Carbocyclic compounds
- C09K2211/1007—Non-condensed systems
-
- 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
- C09K2211/1003—Carbocyclic compounds
- C09K2211/1011—Condensed systems
-
- 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
- C09K2211/1003—Carbocyclic compounds
- C09K2211/1014—Carbocyclic compounds bridged by heteroatoms, e.g. N, P, Si or B
-
- 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
- C09K2211/1037—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom with sulfur
-
- 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
- C09K2211/1092—Heterocyclic compounds characterised by ligands containing sulfur as the only heteroatom
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nanotechnology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Optics & Photonics (AREA)
- Crystallography & Structural Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- General Physics & Mathematics (AREA)
- Manufacturing & Machinery (AREA)
- Materials Engineering (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明属于光疗技术领域，涉及一种具有近红外二区发光特性的多功能光疗剂。该多功能光疗剂为球状核壳结构，以D‑π‑A化合物为核，两亲性聚合物为壳，D‑π‑A化合物由D、π和A三种基团构成，D为电子供体，π为π桥，A为电子受体，D选自结构式I、II、III所示基团中的一种；π选自结构式IV、V、VI所示基团中的一种；A为VII；
该多功能光疗剂同时具有光热和光动力性能，可用于体内成像以及光热和光动力的癌症协同光疗。
Description
技术领域
本发明属于光疗技术领域，涉及一种具有近红外二区发光特性的多功能光疗剂，具有近红外二区荧光成像引导的光热和光动力协同癌症治疗的潜力。
背景技术
全球身患癌症的人数在逐年增加，已成为对人类健康的严重威胁。生物医学的发展已经开辟了癌症治疗的新领域，其中光疗可以在诊断的同时进行原位治疗，这已被证明是癌症治疗的卓越方案。在诊断方面，相比于传统的磁共振成像、计算机断层扫描和X光成像，荧光成像技术具有分辨率较高，侵入性小，响应速度快的特点，特别是近红外二区(1000-1700nm)的荧光成像在生物医学领域受到广泛关注，归因于它较深的组织穿透力、较低的组织自发荧光干扰和较少的组织光损伤。在治疗方面，传统的肿瘤治疗手段的缺陷和后遗症比较多，给人们带来了严重的精神负担，开发一种毒副作用小、治疗效果佳的治疗技术被人们所期待。
光疗(光动力/光热)凭借其毒副作用小、治疗效果好等优点步入人们的眼帘，因其高选择性、无创性、良好的可控性和可忽略的耐药性而受到了广泛关注。光动力治疗主要通过形成活性氧(ROS)破坏肿瘤的血管系统，导致癌细胞缺少供能系统，从而间接的杀死癌细胞。光热治疗依靠具有光热效应的材料将光转换为热，从而使细胞膜变松并使各种蛋白质变性，以不可逆转的方式杀死癌细胞。然而，光动力治疗和光热治疗的效率分别受到肿瘤周围缺氧微环境和残留癌细胞获得性耐热特性的严重抑制，导致单独的光动力治疗或光热治疗效果都不令人满意。因此，目前的癌症研究趋势开始转变为光动力治疗和光热治疗的协同治疗模式，以达到相互增效，取长补短的1+1大于2的协同效果。将具有各自特定属性的各种组分组合到一个纳米平台中，是目前最常用的方法。尽管这种多合一的材料在一定程度上可以满足诊断和治疗，但不可避免的会因其成分复杂、加工性困难、重现性低和药代动力学不确定等因素限制了其在临床上的应用。为了达到临床应用的目的，将所有光疗模式巧妙地整合到制备简单、结构明确、生物相容性和重现性好的单个有机小分子中，是癌症治疗的较好选择。然而现有的多功能光疗剂的发射峰大都位于近红外一区，基本还未有发射峰位于近红外二区的光疗剂。
发明内容
本发明的发明目的在于针对现有技术存在的上述问题，提供一种化合物，以及用该化合物制得的同时具有近红外二区荧光成像、光热治疗和光动力治疗的多功能光疗剂。
为实现上述发明目的，本发明通过如下方案实现：D-π-A化合物，所述D-π-A化合物由D、π和A三种基团构成，D为电子供体，π为π桥，A为电子受体，D选自结构式I、II、III所示基团中的一种；π选自结构式IV、V、VI所示基团中的一种；A为VII；I、II、III、IV、V、VI、VII的结构式如下：
D-π-A化合物的结构式如下：
作为优选，当D为I时，π为IV，V，VI时，D-π-A结构式为C1、C2、C3中的一种，C1、C2、C3的结构式如下：
作为优选，当D为II时，π为IV，V，VI时，D-π-A结构式为C4、C5、C6中的一种，C4、C5、C6的结构式如下：
作为优选，当D为III时，π为IV，V，VI时，D-π-A结构为C7、C8、C9中的一种，C4、C5、C6的结构式如下：
本发明还提供一种具有近红外二区发光特性的多功能光疗剂，所述的多功能光疗剂为球状核壳结构，以上述D-π-A化合物为核，两亲性聚合物为壳。
在上述具有近红外二区发光特性的多功能光疗剂中，两亲性聚合物包括二硬脂酰基磷脂酰乙醇胺-聚乙二醇(DSPE-PEG2000)、聚乳酸-羟基乙酸共聚物(PLGA)、PluronicF127中的一种或多种。
本发明还提供一种上述具有近红外二区发光特性的多功能光疗剂的制备方法，所述的制备方法包括如下步骤：
步骤1：在钯催化剂、无机碱的作用下，在惰性气体保护下，D-B(OH)2和Br-π-CHO进行铃木反应(Suzuki-Miyaura反应)得到化合物D-π-CHO；
步骤2：化合物D-π-CHO和化合物A溶于溶剂，通过缩合反应得固体D-π-A；
步骤3：将溶于有机溶剂的D-π-A和两亲性聚合物倒入水中，超声处理得以D-π-A化合物为核，两亲性聚合物为壳的纳米粒子悬浮液。
在上述具有近红外二区发光特性的多功能光疗剂的制备方法中，步骤1中铃木反应的温度为60-120℃，反应时间为2-24小时。
在上述具有近红外二区发光特性的多功能光疗剂的制备方法中，步骤1中D-B(OH)2、Br-π-CHO、钯催化剂和无机碱的物质的量的比为1：2～5：0.01～0.2：5～20。
作为优选，所述的钯催化剂包括Pd(PPh3)4,、PdCl2,、Pd(OAc)2、Pd(dppf)Cl2中的一种或多种。
作为优选，所述的无机碱包括氢氧化钠、氢氧化钾、碳酸钾、碳酸氢钾、碳酸钠、碳酸氢钠中的一种或多种。
作为优选，步骤1具体为：将D-B(OH)2、Br-π-CHO钯催化剂、无机碱溶于有机溶剂和水中，在惰性气体保护下，加热反应，反应完成后降至室温，经萃取，收集有机相，水洗、干燥、分离提纯得到化合物D-π-CHO。
进一步优选，所述的有机溶剂包括甲苯、二氧六环、四氢呋喃中的一种或多种。
在上述具有近红外二区发光特性的多功能光疗剂的制备方法中，步骤2中缩合反应的温度为40-120℃，反应时间为3-12小时。
在上述具有近红外二区发光特性的多功能光疗剂的制备方法中，步骤2中D-π-CHO、化合物A和溶剂的物质的量比为1：1～5：50～200。
作为优选，所述的溶剂包括乙酸酐、乙醇、乙腈、四氢呋喃中的一种或多种。
在上述具有近红外二区发光特性的多功能光疗剂的制备方法中，步骤3中D-π-A与两亲性聚合物的质量比为1：2～6。
与现有技术相比，本发明具有以下优点：
1.本发明在D-π-A结构中引入了双丙二腈取代的1,3-茚二酮电子受体，该电子受体不仅具有较强的吸电子能力，而且其中的四个氰基具有强烈的分子内伸缩振动，伸缩振动的存在有助于将吸收的光能转化为热能。此外，还引入了三苯胺和噻吩类等较强的电子供体，与电子受体一起形成了较强的分子内电荷转移体系，有助于吸收和发射光谱的红移以及活性氧的产生。
2.本发明用以D-π-A化合物为核，两亲性聚合物为壳的光疗剂具有近红外二区(1000～1700nm)荧光发射，同时具有光热和光动力性能，可用于体内成像以及光热和光动力的癌症协同光疗，在生物医学上具有重大意义。
附图说明
图1为本发明光疗剂的结构示意图；
图2为实施例2中多功能光疗剂C2 NPs的粒径分布和电镜图；
图3为实施例1中多功能光疗剂C1 NPs和实施例2中多功能光疗剂C2 NPs在水溶液中的荧光光谱图；
图4为实施例1中多功能光疗剂C1 NPs和实施例2中多功能光疗剂C2 NPs的水溶液在660nm(0.3W/cm2)激光照射下，每2分钟1,3-二苯基异苯并呋喃(DPBF，可以用作单线态氧探针)在410nm处的吸收的变化；
图5为实施例1中多功能光疗剂C1 NPs和实施例2中多功能光疗剂C2 NPs的水溶液在660nm(1W/cm2)激光照射10分钟后，纳米粒子在水中的光热性能，插图为照射10分钟后相应的红外热图像；
图6为4T1细胞在不同浓度C2NPs下的光毒性和暗毒性。
具体实施方式
实施例1
(1)化合物I-π-CHO的合成：
将5-溴噻吩-2-甲醛(670mg,3.5mmol)、4-(二苯基胺基)苯硼酸(1215mg,4.2mmol)、四(三苯基膦)钯(200mg,0.175mmol)和碳酸钾(2415mg,17.5mmol)溶于1,4-二氧六环(25mL)和去离子水(5mL)的混合溶液中，随后混合物在氮气保护下，85℃搅拌5小时。反应体系降至室温，反应液用二氯甲烷和水萃取，收集有机相，水洗，无水硫酸钠干燥，用旋转蒸发仪减压蒸馏除去有机溶剂，得到粗产物。将粗产物通过硅胶柱层析分离提纯，展开剂为石油醚/二氯甲烷(1:1，v/v)，得到黄色固体(950mg,产率76％)。1H NMR(300MHz,Chloroform-d)δ9.86(d,J＝1.0Hz,1H),7.71(dd,J＝4.0,1.1Hz,1H),7.52(dd,J＝8.3,1.4Hz,2H),7.36-7.27(m,5H),7.19-7.03(m,8H)。
(2)化合物C1的合成：
将化合物I-π-CHO(100mg,0.2813mmol)和化合物A(70mg,0.2813mmol)溶于3mL乙酸酐中，60℃下搅拌6小时。反应体系降至室温，旋干，并用二氯甲烷溶解，加入石油醚使产物析出，过滤得固体C1(135mg,产率83％)。1H NMR(300MHz,Chloroform-d)δ8.65(s,1H),8.58(dd,J＝5.9,3.1Hz,2H),7.78(dd,J＝5.9,3.1Hz,2H),7.65(d,J＝4.1Hz,1H),7.52(d,J＝8.8Hz,2H),7.40-7.28(m,5H),7.22-7.10(m,6H),7.05(d,J＝8.7Hz,2H).13C NMR(151MHz,Chloroform-d)δ160.98,157.93,150.25,146.47,143.08,137.31,136.10,135.06,134.56,129.64,127.79,126.36,125.66,125.51,124.83,124.57,124.15,121.50,113.52,113.45。
(3)C1 NPs的合成：
将包含1mg化合物C1和4mg DSPE-PEG2000的1mL四氢呋喃溶液倒入9mL去离子水中，超声处理5分钟。将以上混合物在通风橱中剧烈搅拌24小时，以除去四氢呋喃，并使用0.22μM注射器式过滤器过滤以获得最终的纳米粒子悬浮液，即为多功能光疗剂。
实施例2
(1)化合物II-π-CHO的合成：
将5-溴噻吩[3,2-b]噻吩-2-甲醛(262mg,1.06mmol)、4-(二苯基胺基)苯硼酸(368mg,1.273mmol)、四(三苯基膦)钯(62mg,0.0536mmol)和碳酸钾(732mg,5.304mmol)溶于1,4-二氧六环(25mL)和去离子水(5mL)的混合溶液中，随后混合物在氮气保护下，80℃搅拌5小时。反应体系降至室温，反应液用二氯甲烷和水萃取，收集有机相，水洗，无水硫酸钠干燥，用旋转蒸发仪减压蒸馏除去有机溶剂，得到粗产物。将粗产物通过硅胶柱层析分离提纯，展开剂为石油醚/二氯甲烷(1:1，v/v)，得到黄色固体(325mg,产率75％)。1H NMR(600MHz,Chloroform-d)δ9.92(d,J＝1.6Hz,1H),7.87(d,J＝1.9Hz,1H),7.51-7.46(m,2H),7.40(d,J＝1.9Hz,1H),7.29(dd,J＝8.5,7.3Hz,4H),7.16-7.11(m,4H),7.08(td,J＝8.8,8.1,2.6Hz,4H)。
(2)化合物C2的合成：
将化合物II-π-CHO(50mg,0.1215mmol)和化合物A(33mg,0.1336mmol)溶于2mL乙酸酐中，60℃下搅拌6小时。反应体系降至室温，旋干，并用二氯甲烷溶解，加入石油醚使产物析出，过滤得固体C2(63mg,产率82％)。1H NMR(300MHz,Chloroform-d)δ8.73(s,1H),8.57(dd,J＝5.9,3.2Hz,2H),7.87-7.71(m,3H),7.57-7.45(m,2H),7.39(s,1H),7.37-7.27(m,4H),7.23-7.00(m,8H).13C NMR(151MHz,Chloroform-d)δ159.74,155.89,149.41,148.56,145.67,138.05,136.88,136.22,135.70,133.53,132.48,128.54,126.20,125.42,125.02,124.45,123.23,120.80,113.32,112.45。
(3)C2NPs的合成：
将包含1mg化合物C2和4mg DSPE-PEG2000的1mL四氢呋喃溶液倒入9mL去离子水中，超声处理5分钟。将以上混合物在通风橱中剧烈搅拌24小时，以除去四氢呋喃，并使用0.22μM注射器式过滤器过滤以获得最终的纳米粒子悬浮液，即为多功能光疗剂。
实施例2中多功能光疗剂C2 NPs的粒径分布和电镜图如图2所示，从图中可得化合物C2 NPs平均尺寸为72.8nm，TEM图显示C2 NPs的形态为近似球形。
实施例1和实施例2中的多功能光疗剂C1 NPs和C2 NPs在水溶液中的荧光光谱图如图3所示，从图中可得两者的发射峰几乎都位于近红外二区。
实施例1多功能光疗剂C1 NPs和实施例2中多功能光疗剂C2 NPs的水溶液在660nm(0.3W/cm2)激光照射下，每2分钟1,3-二苯基异苯并呋喃(DPBF,可以用作单线态氧探针)在410nm处的吸收的变化如图4所示。从图4中可以看出，C1 NPs和C2 NPs都具有单线态氧产生能力。
实施例1多功能光疗剂C1 NPs和实施例2中多功能光疗剂C2 NPs的水溶液在660nm(1W/cm2)激光照射10分钟后，纳米粒子在水中的光热性能如图5所示，插图为照射10分钟后相应的红外热图像。从图5中可以看出，C1 NPs和C2 NPs均表现出较好的光热效果。
4T1细胞在不同浓度C2 NPs下的光毒性和暗毒性如图6所示。从图6中可以看出，C2NPs具有良好的生物相容性以及在660nm激光照射下具有对癌细胞的杀伤作用。
综上所述，本发明用以D-π-A化合物为核，两亲性聚合物为壳的光疗剂具有近红外二区(1000～1700nm)荧光发射，同时具有光热和光动力性能，可用于体内成像以及光热和光动力的癌症协同光疗，在生物医学上具有重大意义。
以上为本发明所述的具体实施方式，并不用于限制本发明，对于本领域的技术人员来说，本发明可以有各种更改和变化。凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。
Claims (10)
1.D-π-A化合物，其特征在于，所述D-π-A化合物由D、π和A三种基团构成，D为电子供体，π为π桥，A为电子受体，D选自结构式I、II、III所示基团中的一种；π选自结构式IV、V、VI所示基团中的一种；A为VII；I、II、III、IV、V、VI、VII的结构式如下：
2.一种具有近红外二区发光特性的多功能光疗剂，其特征在于，所述的多功能光疗剂为球状核壳结构，以权利要求1所述的D-π-A化合物为核，两亲性聚合物为壳。
3.根据权利要求2所述的具有近红外二区发光特性的多功能光疗剂，其特征在于，两亲性聚合物包括二硬脂酰基磷脂酰乙醇胺-聚乙二醇(DSPE-PEG2000)、聚乳酸-羟基乙酸共聚物(PLGA)、Pluronic F127中的一种或多种。
4.一种如权利要求2所述的具有近红外二区发光特性的多功能光疗剂的制备方法，其特征在于，所述的制备方法包括如下步骤：
步骤1：在钯催化剂、无机碱的作用下，在惰性气体保护下，D-B(OH)2和Br-π-CHO进行铃木反应(Suzuki-Miyaura反应)得到化合物D-π-CHO；
步骤2：化合物D-π-CHO和化合物A溶于溶剂，通过缩合反应得固体D-π-A；
步骤3：将溶于有机溶剂的D-π-A和两亲性聚合物倒入水中，超声处理得以D-π-A化合物为核，两亲性聚合物为壳的纳米粒子悬浮液。
5.根据权利要求4所述的具有近红外二区发光特性的多功能光疗剂的制备方法，其特征在于，步骤1中铃木反应的温度为60-120℃，反应时间为2-24小时。
6.根据权利要求4所述的具有近红外二区发光特性的多功能光疗剂的制备方法，其特征在于，步骤1中D-B(OH)2、Br-π-CHO、钯催化剂和无机碱的物质的量的比为1：2～5：0.01～0.2：5～20。
7.根据权利要求4或6所述的具有近红外二区发光特性的多功能光疗剂的制备方法，其特征在于，所述的钯催化剂包括Pd(PPh3)4,、PdCl2,、Pd(OAc)2、Pd(dppf)Cl2中的一种或多种。
8.根据权利要求4或6所述的具有近红外二区发光特性的多功能光疗剂的制备方法，其特征在于，所述的无机碱包括氢氧化钠、氢氧化钾、碳酸钾、碳酸氢钾、碳酸钠、碳酸氢钠中的一种或多种。
9.根据权利要求4所述的具有近红外二区发光特性的多功能光疗剂的制备方法，其特征在于，步骤2中缩合反应的温度为40-120℃，反应时间为3-12小时。
10.根据权利要求4所述的具有近红外二区发光特性的多功能光疗剂的制备方法，其特征在于，步骤2中D-π-CHO、化合物A和溶剂的物质的量比为1：1～5：50～200，所述的溶剂包括乙酸酐、乙醇、乙腈、四氢呋喃中的一种或多种。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210324354.6A CN114805293A (zh) | 2022-03-30 | 2022-03-30 | D-π-A化合物、含有该化合物的具有近红外二区发光特性的多功能光疗剂 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210324354.6A CN114805293A (zh) | 2022-03-30 | 2022-03-30 | D-π-A化合物、含有该化合物的具有近红外二区发光特性的多功能光疗剂 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114805293A true CN114805293A (zh) | 2022-07-29 |
Family
ID=82532987
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210324354.6A Pending CN114805293A (zh) | 2022-03-30 | 2022-03-30 | D-π-A化合物、含有该化合物的具有近红外二区发光特性的多功能光疗剂 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114805293A (zh) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111978313A (zh) * | 2020-08-28 | 2020-11-24 | 深圳大学 | 具备聚集诱导发光性质的多模态光诊疗剂及其制备与应用 |
| CN112920113A (zh) * | 2021-01-22 | 2021-06-08 | 华南理工大学 | 一种靶向β淀粉样蛋白的荧光探针及制备以及其在阿尔兹海默症中的应用 |
| CN113372339A (zh) * | 2021-05-19 | 2021-09-10 | 三峡大学 | 光动力/光热双功能化合物ns-stpa及其应用 |
| CN113845519A (zh) * | 2021-09-18 | 2021-12-28 | 山西大学 | 一种微环境敏感型荧光探针及其制备方法和应用 |
| CN114040962A (zh) * | 2019-06-18 | 2022-02-11 | 香港科技大学 | 用于细胞器成像的发射红色荧光的化合物 |
| CN114213419A (zh) * | 2021-11-29 | 2022-03-22 | 内蒙古大学 | 一种兼具荧光成像和i型光动力/光热杀伤癌细胞活性的荧光探针及其制备方法和应用 |
-
2022
- 2022-03-30 CN CN202210324354.6A patent/CN114805293A/zh active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114040962A (zh) * | 2019-06-18 | 2022-02-11 | 香港科技大学 | 用于细胞器成像的发射红色荧光的化合物 |
| CN111978313A (zh) * | 2020-08-28 | 2020-11-24 | 深圳大学 | 具备聚集诱导发光性质的多模态光诊疗剂及其制备与应用 |
| CN112920113A (zh) * | 2021-01-22 | 2021-06-08 | 华南理工大学 | 一种靶向β淀粉样蛋白的荧光探针及制备以及其在阿尔兹海默症中的应用 |
| CN113372339A (zh) * | 2021-05-19 | 2021-09-10 | 三峡大学 | 光动力/光热双功能化合物ns-stpa及其应用 |
| CN113845519A (zh) * | 2021-09-18 | 2021-12-28 | 山西大学 | 一种微环境敏感型荧光探针及其制备方法和应用 |
| CN114213419A (zh) * | 2021-11-29 | 2022-03-22 | 内蒙古大学 | 一种兼具荧光成像和i型光动力/光热杀伤癌细胞活性的荧光探针及其制备方法和应用 |
Non-Patent Citations (5)
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114213419B (zh) | 一种兼具荧光成像和i型光动力/光热杀伤癌细胞活性的荧光探针及其制备方法和应用 | |
| CN103626781B (zh) | 一种靶向抗癌分子吉非替尼酞菁轭合物及其制备和应用 | |
| CN113773667B (zh) | 有机小分子近红外二区荧光染料及其制备方法和应用 | |
| CN108864106A (zh) | 新型近红外二区有机小分子荧光探针的制备与应用 | |
| JP2009505968A (ja) | ペリレンキノン誘導体及びその使用 | |
| CN111978313A (zh) | 具备聚集诱导发光性质的多模态光诊疗剂及其制备与应用 | |
| CN107722024B (zh) | 胺基苯氧基取代酞菁及其在制药领域中的应用 | |
| CN108948060B (zh) | 三苯胺基树枝配体取代硅酞菁及其制备方法和应用 | |
| CN105585872B (zh) | 一种不对称近红外菁染料及其制备方法与应用 | |
| Hu et al. | A thermally activated delayed fluorescence photosensitizer for photodynamic therapy of oral squamous cell carcinoma under low laser intensity | |
| CN109369633B (zh) | 一种可靶向线粒体的近红外二区荧光化合物及其制备方法与应用 | |
| CN105622682B (zh) | 一种羧基酞菁锌-阿霉素偶联物及其制备和应用 | |
| Chen et al. | Development of novel nanoporphyrin biomaterials for NIR-II activated photothermal therapy against tumor in vivo | |
| CN114805293A (zh) | D-π-A化合物、含有该化合物的具有近红外二区发光特性的多功能光疗剂 | |
| CN103073553B (zh) | 水溶性萘菁基化合物、制备方法及作为光敏剂的应用 | |
| CN115109081A (zh) | 一种辣椒素衍生化光敏剂及其制备方法与应用 | |
| CN108715591A (zh) | 用作光敏剂的近红外吸收卟啉化合物及其应用 | |
| CN109456334B (zh) | 周环单取代两亲性酞菁光敏剂及其制备和应用 | |
| Zhang et al. | Organic nanoparticles based on aza-boron dipyrromethene derivatives for combined photothermal and photodynamic cancer therapy | |
| CN104826111A (zh) | 上转换NaYF4:Yb3+,Tm3+纳米晶体-竹红菌素复合物的制备方法及制得的复合物在光敏治疗中的应用 | |
| CN115246845B (zh) | 一种D-π-A-π-D型近红外二区聚集诱导发光分子、纳米制剂及其应用 | |
| CN118027124B (zh) | 一种尿苷修饰钌(ii)配合物及其制备方法和作为光动力治疗光敏剂的应用 | |
| CN113636988B (zh) | 一种硒代吲哚菁绿衍生物及其制备方法和应用 | |
| CN115785112B (zh) | 一种香豆素半花菁类光敏剂及其制备方法和应用 | |
| CN114409710B (zh) | Nir-ii多吡啶钌配合物及其制备方法和应用 |
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 | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20220729 |