CN109432452A - The preparation method and products thereof of oxygen sensitive type multifunctional nano probe - Google Patents
The preparation method and products thereof of oxygen sensitive type multifunctional nano probe Download PDFInfo
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- CN109432452A CN109432452A CN201811610778.9A CN201811610778A CN109432452A CN 109432452 A CN109432452 A CN 109432452A CN 201811610778 A CN201811610778 A CN 201811610778A CN 109432452 A CN109432452 A CN 109432452A
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- oxygen sensitive
- type multifunctional
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 239000001301 oxygen Substances 0.000 title claims abstract description 41
- 229910052760 oxygen Inorganic materials 0.000 title claims abstract description 41
- 239000000523 sample Substances 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 239000000463 material Substances 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 4
- 230000004048 modification Effects 0.000 claims abstract description 3
- 238000012986 modification Methods 0.000 claims abstract description 3
- 239000000243 solution Substances 0.000 claims description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 239000002105 nanoparticle Substances 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 235000019441 ethanol Nutrition 0.000 claims description 11
- -1 prevents its reunion Substances 0.000 claims description 11
- 238000005253 cladding Methods 0.000 claims description 10
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 7
- 125000003368 amide group Chemical group 0.000 claims description 7
- 238000004132 cross linking Methods 0.000 claims description 7
- 239000012535 impurity Substances 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 7
- 239000010949 copper Substances 0.000 claims description 6
- 239000008367 deionised water Substances 0.000 claims description 6
- 229910021641 deionized water Inorganic materials 0.000 claims description 6
- 238000004108 freeze drying Methods 0.000 claims description 6
- 150000001298 alcohols Chemical class 0.000 claims description 5
- GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 claims description 5
- 229920001223 polyethylene glycol Polymers 0.000 claims description 5
- RBTBFTRPCNLSDE-UHFFFAOYSA-N 3,7-bis(dimethylamino)phenothiazin-5-ium Chemical compound C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 RBTBFTRPCNLSDE-UHFFFAOYSA-N 0.000 claims description 4
- ZGXJTSGNIOSYLO-UHFFFAOYSA-N 88755TAZ87 Chemical compound NCC(=O)CCC(O)=O ZGXJTSGNIOSYLO-UHFFFAOYSA-N 0.000 claims description 4
- UJKPHYRXOLRVJJ-MLSVHJFASA-N CC(O)C1=C(C)/C2=C/C3=N/C(=C\C4=C(CCC(O)=O)C(C)=C(N4)/C=C4\N=C(\C=C\1/N\2)C(C)=C4C(C)O)/C(CCC(O)=O)=C3C Chemical class CC(O)C1=C(C)/C2=C/C3=N/C(=C\C4=C(CCC(O)=O)C(C)=C(N4)/C=C4\N=C(\C=C\1/N\2)C(C)=C4C(C)O)/C(CCC(O)=O)=C3C UJKPHYRXOLRVJJ-MLSVHJFASA-N 0.000 claims description 4
- PQMOXTJVIYEOQL-UHFFFAOYSA-N Cumarin Natural products CC(C)=CCC1=C(O)C(C(=O)C(C)CC)=C(O)C2=C1OC(=O)C=C2CCC PQMOXTJVIYEOQL-UHFFFAOYSA-N 0.000 claims description 4
- FSOGIJPGPZWNGO-UHFFFAOYSA-N Meomammein Natural products CCC(C)C(=O)C1=C(O)C(CC=C(C)C)=C(O)C2=C1OC(=O)C=C2CCC FSOGIJPGPZWNGO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 229960000907 methylthioninium chloride Drugs 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- YFSUTJLHUFNCNZ-UHFFFAOYSA-N perfluorooctane-1-sulfonic acid Chemical compound OS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F YFSUTJLHUFNCNZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003504 photosensitizing agent Substances 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000007789 gas Substances 0.000 claims description 3
- CCEKAJIANROZEO-UHFFFAOYSA-N sulfluramid Chemical compound CCNS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F CCEKAJIANROZEO-UHFFFAOYSA-N 0.000 claims description 3
- 229940124530 sulfonamide Drugs 0.000 claims description 3
- QGTQTQBVAMFOGO-UHFFFAOYSA-N 1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluorooctane-1-sulfonic acid;potassium Chemical compound [K].OS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F QGTQTQBVAMFOGO-UHFFFAOYSA-N 0.000 claims description 2
- MHIITNFQDPFSES-UHFFFAOYSA-N 25,26,27,28-tetrazahexacyclo[16.6.1.13,6.18,11.113,16.019,24]octacosa-1(25),2,4,6,8(27),9,11,13,15,17,19,21,23-tridecaene Chemical class N1C(C=C2C3=CC=CC=C3C(C=C3NC(=C4)C=C3)=N2)=CC=C1C=C1C=CC4=N1 MHIITNFQDPFSES-UHFFFAOYSA-N 0.000 claims description 2
- QXYRRCOJHNZVDJ-UHFFFAOYSA-N 4-pyren-1-ylbutanoic acid Chemical compound C1=C2C(CCCC(=O)O)=CC=C(C=C3)C2=C2C3=CC=CC2=C1 QXYRRCOJHNZVDJ-UHFFFAOYSA-N 0.000 claims description 2
- OSBSXTGABLIDRX-UHFFFAOYSA-N 5-methylidenecyclohexa-1,3-diene Chemical compound C=C1CC=CC=C1 OSBSXTGABLIDRX-UHFFFAOYSA-N 0.000 claims description 2
- 244000003416 Asparagus officinalis Species 0.000 claims description 2
- 235000005340 Asparagus officinalis Nutrition 0.000 claims description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 claims description 2
- AZJORUUUJDFLLN-UHFFFAOYSA-N C12=CC=C(N1)C=C1C=CC(=N1)C=C1C=CC(N1)=CC=1C3=C(C(N1)=C2)C=CC=C3.C32=CC=C(N3)C=C3C=CC(=N3)C=C3C=CC(N3)=CC=3C=CC(N3)=C2.C2=CC=CC=C2 Chemical class C12=CC=C(N1)C=C1C=CC(=N1)C=C1C=CC(N1)=CC=1C3=C(C(N1)=C2)C=CC=C3.C32=CC=C(N3)C=C3C=CC(=N3)C=C3C=CC(N3)=CC=3C=CC(N3)=C2.C2=CC=CC=C2 AZJORUUUJDFLLN-UHFFFAOYSA-N 0.000 claims description 2
- QIFLLJSAJFLLRE-UHFFFAOYSA-N C1=CC=CC2=CC3=CC=CC=C3C=C12.[F] Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C12.[F] QIFLLJSAJFLLRE-UHFFFAOYSA-N 0.000 claims description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 2
- UVAUHTUDFIJIDS-UHFFFAOYSA-N FC(C(C(C(F)(F)F)(F)F)(F)F)([K])F Chemical compound FC(C(C(C(F)(F)F)(F)F)(F)F)([K])F UVAUHTUDFIJIDS-UHFFFAOYSA-N 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 2
- MYQVHPRJHDLQNH-UHFFFAOYSA-N [K].OS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F Chemical compound [K].OS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F MYQVHPRJHDLQNH-UHFFFAOYSA-N 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 229940107816 ammonium iodide Drugs 0.000 claims description 2
- UAWBWGUIUMQJIT-UHFFFAOYSA-N azanium;1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluorooctane-1-sulfonate Chemical compound N.OS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F UAWBWGUIUMQJIT-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- SURLGNKAQXKNSP-DBLYXWCISA-N chlorin Chemical compound C\1=C/2\N/C(=C\C3=N/C(=C\C=4NC(/C=C\5/C=CC/1=N/5)=CC=4)/C=C3)/CC\2 SURLGNKAQXKNSP-DBLYXWCISA-N 0.000 claims description 2
- 150000004699 copper complex Chemical class 0.000 claims description 2
- 150000002170 ethers Chemical class 0.000 claims description 2
- 239000012894 fetal calf serum Substances 0.000 claims description 2
- 229960003569 hematoporphyrin Drugs 0.000 claims description 2
- MPGWGYQTRSNGDD-UHFFFAOYSA-N hypericin Chemical compound OC1=CC(O)=C(C2=O)C3=C1C1C(O)=CC(=O)C(C4=O)=C1C1=C3C3=C2C(O)=CC(C)=C3C2=C1C4=C(O)C=C2C MPGWGYQTRSNGDD-UHFFFAOYSA-N 0.000 claims description 2
- 229940005608 hypericin Drugs 0.000 claims description 2
- PHOKTTKFQUYZPI-UHFFFAOYSA-N hypericin Natural products Cc1cc(O)c2c3C(=O)C(=Cc4c(O)c5c(O)cc(O)c6c7C(=O)C(=Cc8c(C)c1c2c(c78)c(c34)c56)O)O PHOKTTKFQUYZPI-UHFFFAOYSA-N 0.000 claims description 2
- WIQKYZYFTAEWBF-UHFFFAOYSA-L motexafin lutetium hydrate Chemical compound O.[Lu+3].CC([O-])=O.CC([O-])=O.C1=C([N-]2)C(CC)=C(CC)C2=CC(C(=C2C)CCCO)=NC2=CN=C2C=C(OCCOCCOCCOC)C(OCCOCCOCCOC)=CC2=NC=C2C(C)=C(CCCO)C1=N2 WIQKYZYFTAEWBF-UHFFFAOYSA-L 0.000 claims description 2
- RLKHFSNWQCZBDC-UHFFFAOYSA-N n-(benzenesulfonyl)-n-fluorobenzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)N(F)S(=O)(=O)C1=CC=CC=C1 RLKHFSNWQCZBDC-UHFFFAOYSA-N 0.000 claims description 2
- 229950011087 perflunafene Drugs 0.000 claims description 2
- LUYQYZLEHLTPBH-UHFFFAOYSA-N perfluorobutanesulfonyl fluoride Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)S(F)(=O)=O LUYQYZLEHLTPBH-UHFFFAOYSA-N 0.000 claims description 2
- UWEYRJFJVCLAGH-IJWZVTFUSA-N perfluorodecalin Chemical compound FC1(F)C(F)(F)C(F)(F)C(F)(F)[C@@]2(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)[C@@]21F UWEYRJFJVCLAGH-IJWZVTFUSA-N 0.000 claims description 2
- 150000004032 porphyrins Chemical class 0.000 claims description 2
- SSKVDVBQSWQEGJ-UHFFFAOYSA-N pseudohypericin Natural products C12=C(O)C=C(O)C(C(C=3C(O)=CC(O)=C4C=33)=O)=C2C3=C2C3=C4C(C)=CC(O)=C3C(=O)C3=C(O)C=C(O)C1=C32 SSKVDVBQSWQEGJ-UHFFFAOYSA-N 0.000 claims description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 2
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 claims description 2
- 229950003937 tolonium Drugs 0.000 claims description 2
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 claims description 2
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical compound CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 claims 2
- 150000003456 sulfonamides Chemical class 0.000 claims 2
- HSDJWNJDPDJOEV-UHFFFAOYSA-N 1,1,2,2,3,3,4,4,5,5,6,6,6-tridecafluorohexane-1-sulfonyl fluoride Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)S(F)(=O)=O HSDJWNJDPDJOEV-UHFFFAOYSA-N 0.000 claims 1
- VIQJCEGYVDRIKL-UHFFFAOYSA-N C(CCCCCCC)S(=O)(=O)N.[F] Chemical compound C(CCCCCCC)S(=O)(=O)N.[F] VIQJCEGYVDRIKL-UHFFFAOYSA-N 0.000 claims 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 1
- 125000005250 alkyl acrylate group Chemical group 0.000 claims 1
- 229910001882 dioxygen Inorganic materials 0.000 claims 1
- 229960004756 ethanol Drugs 0.000 claims 1
- HMRWGKIZOBXNRB-UHFFFAOYSA-N octane-1-sulfonyl fluoride Chemical compound CCCCCCCCS(F)(=O)=O HMRWGKIZOBXNRB-UHFFFAOYSA-N 0.000 claims 1
- 229950008618 perfluamine Drugs 0.000 claims 1
- JAJLKEVKNDUJBG-UHFFFAOYSA-N perfluorotripropylamine Chemical compound FC(F)(F)C(F)(F)C(F)(F)N(C(F)(F)C(F)(F)C(F)(F)F)C(F)(F)C(F)(F)C(F)(F)F JAJLKEVKNDUJBG-UHFFFAOYSA-N 0.000 claims 1
- 125000001453 quaternary ammonium group Chemical group 0.000 claims 1
- 206010021143 Hypoxia Diseases 0.000 abstract description 3
- 206010028980 Neoplasm Diseases 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 230000007954 hypoxia Effects 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 230000008569 process Effects 0.000 abstract description 2
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 7
- 230000002685 pulmonary effect Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000002539 nanocarrier Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 2
- XZXYQEHISUMZAT-UHFFFAOYSA-N 2-[(2-hydroxy-5-methylphenyl)methyl]-4-methylphenol Chemical compound CC1=CC=C(O)C(CC=2C(=CC=C(C)C=2)O)=C1 XZXYQEHISUMZAT-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 238000011155 quantitative monitoring Methods 0.000 description 1
- 238000002601 radiography Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
- A61K49/225—Microparticles, microcapsules
-
- 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
- A61K41/0071—PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
-
- 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
- A61K41/0076—PDT with expanded (metallo)porphyrins, i.e. having more than 20 ring atoms, e.g. texaphyrins, sapphyrins, hexaphyrins, pentaphyrins, porphocyanines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The present invention relates to a kind of preparation methods and products thereof of oxygen sensitive type multifunctional nano probe, the probe is based on oxygen sensitive material, package and modification by biomolecule, pass through compound, the formation biocompatibility oxygen sensitive type multifunctional nano probe with photosensitive molecular and fluorocarbons again.By oxygen sensitive type multifunctional nano probe, tissue and O can be probed into2The relationship of concentration relationship is advantageously applied to the tumour for the treatment of micro-environmental hypoxia.Preparation method simple process in the present invention, strong operability can further satisfaction production and application.
Description
Technical field
The present invention relates to the preparation field of nano material, it is specifically related to a kind of oxygen sensitive type multifunctional nano probe
Preparation method and products thereof.
Background technique
In recent years, pulmonary administration causes researchers and more and more pays close attention to and study.Nano-carrier system is in lung
There is lot of advantages in administration.As can distributing in the drug of the relatively uniform dosage of alveolar, which has slow releasing function, with it
Solubility in water phase is compared, and can achieve higher drug solubility.Exactly because having many advantages, nano-carrier system
Pulmonary administration, they are considered as the best method for treating pulmonary disease.
PLGA is a kind of high-molecular compound, its internal safety is very good.It is minimum to human health damage, because
Its catabolite is the metabolite of human body, does not influence the normal physiological activity of human body.In addition to this, the property of PLGA encystation balling-up
It can be also very good.In terms of pulmonary administration, compared with traditional liposome, PLGA have the characteristics that it is more excellent, as PLGA can
With more slow release payload material, the drug of encapsulating also has the activity of longer time, and has in vitro and in vivo more stable
Physics and chemical manifestations.In addition, internal targeting and long periodicity may be implemented in modified PLGA, it can also be by adjusting poly- cream
Acid adjusts its biological degradability with ratio, molecular weight and the chemical structure of glycolic.In conclusion PLGA is after pulmonary administration
Research in also show that its Potential Vector as pulmonary administration, future will have bigger application prospect.
For the progress of PLGA such a excellent performance and current cancer therapies drug, anoxic used in clinic
Property lung carcinoma cell therapeutic strategy has fluoroscopic visualization molecule nano probe, PET functional molecular nano-probe, MRI molecule nano probe
The drawbacks of exploitation with photochemical and thermal reaction photodynamic therapy, these new function molecule nano probes overcomes Conventional diagnostic mode,
Make it possible noninvasive radiography, but anoxic treatment curative effect and O2Quantitative relationship between concentration is still failed to obtain and explicitly be examined
Treatment scheme is realized and is treated to oncotherapy the present invention is directed to probe into develop a kind of Hypoxic oncotherapy functional molecular nano-probe
Effect and O2The Quantitative Monitoring of concentration.
Summary of the invention
Aiming at the shortcomings in the prior art, it is an object of that present invention to provide a kind of oxygen sensitive type multifunctional nano probes
Preparation method.
Another object of the present invention is: the oxygen sensitive type multifunctional nano probe for providing a kind of above method preparation produces
Product.
The object of the invention is realized by following proposal: a kind of preparation method of oxygen sensitive type multifunctional nano probe, with
Based on oxygen sensitive material, package and modification by biomolecule, then by being answered with photosensitive molecular and fluorocarbons
It closes, forms oxygen sensitive type multifunctional nano probe, include the following steps, number refers to mass fraction in following steps:
A, amino-contained outer cladding solution is prepared, solution, which is added in oxygen sensitive material solution, prevents its reunion, nitrogen protection gas
It is stirred at room temperature under atmosphere, obtains mixed solution；
B, in mixed solution obtained by the step a for being dissolved in photosensitizer, 2 ~ 4 parts of straight alcohols and 0 ~ 4 part of fluorocarbons is then added.
C, the amido in glutaraldehyde cross-linking external cladding material is added, it is molten to obtain nanoparticle with deionized water removal impurity
Liquid, freeze-drying form powder, obtain target product oxygen sensitive type multifunctional nano probe.
Wherein, the outer cladding solution is amido polyethylene glycol (NH2-PEG), fetal calf serum albumen (BSA), containing ammonia
At least one of propyl-triethoxysilicane phosphatide (APTES).
On the basis of above scheme, in the step a, the amino-contained outer cladding solution of 25mg/mL is prepared, it is molten by 7.5 parts
Liquid, which is added in oxygen sensitive material solution, prevents its reunion, and 12h is stirred at room temperature under nitrogen protection atmosphere.
On the basis of above scheme, the oxygen sensitive material is pyrene, pyrene butyric acid, fluorine anthracene, cumarin, neighbour Fei Luolin spread out
One kind of biology and copper complex ([Cu (POP) (ptpm)] BF4).
In the step b, the photosensitizer of 200 part of 5 mg/mL is dissolved in 2 ~ 4 parts of step a acquired solution, then plus
Enter 2 ~ 4 parts of straight alcohols and 0 ~ 4 part of fluorocarbons.
On the basis of above scheme, the photosensitive agent material is hematoporphyrin derivative (HPD), dihematoporphyrin ethers (DHE)
5-ALA (5-ALA), m- tetrahydroxy phenyl chlorin (m-TH-PC), etioporphyrin (ETIO) tin (SnEtz), methylene blue
(methylene blue) and methylene benzene blue (toluidine blue), benzene porphyrin (benzoporphyrin) derivative and
Lutelium texaphyrins(Lu-Tex), benzoporphyrin derivative mono-acid (BPD-MA), phthalein blueness class
(Phthalocyanines), get Ke Sa porphyrin (Texaphyrins), N- lucid asparagus acyl group chlorin (Npe6), hypericin
(hypercin), one of hematoporphyrin monomethyl ether (HMME) and IR780.
On the basis of above scheme, the fluorocarbons is perfluoro butyl sulfonic acid fluoride (FC-4), perfluoro capryl sulphonyl
Fluorine (FC-8), sulfluramid (FC-9), N- ethylperfluoro octyl sulfonamide ethyl alcohol (FC-10), perfluoro octyl sulfonic acid potassium (FC-95),
Perfluorobutyl potassium sulfonate (FC-98), perfluorinated octyl sulfuryl amine (FC-99), perfluoro octyl sulfonic acid ammonium (FC-120), perfluoro capryl season
Ammonium iodide (FC-134), perfluoro octyl sulfonic acid tetraethyl amine (FC-248), N- perfluoroalkyl group sulfonyl, propyl-triethoxysilicane
Alkane (FC-922), perfluor alkane (FC-40), perfluoroalkyl acrylate (FC-14), N- fluorobenzenesulfonimide, perfluoro hexyl sulphonyl
It is fluorine, perfluorohexanesulfonic acid potassium, N- methyl perfluoro hexyl sulfonamide, N- methyl perfluoro hexyl sulfoamido ethyl alcohol, perfluorodecalin, complete
At least one of fluorine tripropyl amine (TPA).
In the step c, the amido in the glutaraldehyde cross-linking external cladding material of 3.67 part of 25% concentration is added, uses afterwards for 24 hours
Deionized water removal impurity obtains nano-particle solution, and freeze-drying forms powder.
The present invention also provides a kind of oxygen sensitive type multifunctional nano probes, are prepared into according to any of the above-described the method
It arrives.The present invention provides a kind of oxygen sensitive type multifunctional nano probe of biocompatibility based on oxygen sensitive material.
The present invention has the advantages that the present invention can probe into tissue and O by oxygen sensitive type multifunctional nano probe2
The relationship of concentration relationship is advantageously applied to the tumour for the treatment of micro-environmental hypoxia.Preparation method simple process in the present invention, can
Strong operability, can further satisfaction production and application.
Detailed description of the invention
Fig. 1 is the resulting oxygen sensitive type multifunctional nano probe SEM of the embodiment of the present invention 1 figure.
Specific embodiment
Below by way of specific embodiment, the technical scheme of the present invention will be further described.Embodiment below is to this
The further explanation of invention, and do not limit the scope of the invention.
Embodiment 1
A kind of oxygen sensitive type multifunctional nano probe by the package of biomolecule and is repaired based on oxygen sensitive material
Change, then by compound, the formation oxygen sensitive type multifunctional nano probe with photosensitive molecular and fluorocarbons, as follows
Preparation:
By 7.5 parts, the NH2-PEG solution of 25mg/mL, which is added in pyrene solution, prevents its reunion, is stirred at room temperature under nitrogen protection atmosphere
12h obtains NH2-PEG- pyrene nanoparticle.
The TR780 of 200 part of 5 mg/mL is dissolved in 2 parts of NH2-PEG- pyrene nano-particle solution, then 2 parts of addition is pure
Ethyl alcohol and 1 part of FC-4.
The glutaraldehyde cross-linking NH2-PEG-MnO of 3.67 part of 25% concentration is added2Amido, removed afterwards with deionized water for 24 hours
Impurity obtains nano-particle solution, and freeze-drying forms powder.Resulting oxygen sensitive type multifunctional nano probe SEM figure is shown in Fig. 1.
Embodiment 2
A kind of oxygen sensitive type multifunctional nano probe, it is identical as 1 step of embodiment, it prepares as follows:
By 7.5 parts, the BSA solution of 25mg/mL, which is added in [Cu (POP) (ptpm)] BF4 solution, prevents its reunion, nitrogen protection gas
12h is stirred at room temperature under atmosphere, obtain BSA- [Cu (POP) (ptpm)] BF4 nanoparticle.
The BPD-MA of 200 part of 5 mg/mL is dissolved in 4 parts BSA- [Cu (POP) (ptpm)] BF4 nano-particle solution,
Then 4 parts of straight alcohols are added.
The amido of glutaraldehyde cross-linking BSA- [Cu (POP) (ptpm)] BF4 of 3.67 part of 25% concentration is added, spends afterwards for 24 hours
Ionized water removal impurity obtains nano-particle solution, and freeze-drying forms powder.
Embodiment 3
A kind of oxygen sensitive type multifunctional nano probe, it is identical as 1 step of embodiment, it prepares as follows:
By 7.5 parts, the APTES solution of 25mg/mL, which is added in cumarin solution, prevents its reunion, and room temperature is stirred under nitrogen protection atmosphere
12h is mixed, obtain APTES-cumarin nanoparticle.
The HPD of 200 part of 5 mg/mL is dissolved in 4 parts of APTES- cumarin nano-particle solution, then 4 parts of addition is pure
Ethyl alcohol and 4 parts of FC-10.
Glutaraldehyde cross-linking APTES-cumarin amido of 3.67 part of 25% concentration is added, is removed afterwards with deionized water for 24 hours
Impurity obtains nano-particle solution, and freeze-drying forms powder.
Claims (9)
1. a kind of preparation method of oxygen sensitive type multifunctional nano probe, which is characterized in that based on oxygen sensitive material,
Package and modification by biomolecule, then by compound with photosensitive molecular and fluorocarbons, it is more to form oxygen sensitive type
Function nano probe, includes the following steps, number refers to mass fraction in following steps:
A, amino-contained outer cladding solution is prepared, solution, which is added in oxygen sensitive material solution, prevents its reunion, nitrogen protection gas
It is stirred at room temperature under atmosphere, obtains mixed solution；
B, in mixed solution obtained by the step a for being dissolved in photosensitizer, 2 ~ 4 parts of straight alcohols and 0 ~ 4 part of fluorocarbons is then added.
C, the amido in glutaraldehyde cross-linking external cladding material is added, obtains nano-particle solution with deionized water removal impurity, freezes
Form obtains target product oxygen sensitive type multifunctional nano probe at powder.
2. the preparation method of oxygen sensitive type multifunctional nano probe according to claim 1, which is characterized in that described is outer
Cladding solution is amido polyethylene glycol (NH2-PEG), fetal calf serum albumen (BSA), phosphatide containing aminopropyl triethoxysilane
At least one of (APTES).
3. the preparation method of oxygen sensitive type multifunctional nano probe according to claim 1 or claim 2, which is characterized in that described
In step a, the amino-contained outer cladding solution of 25mg/mL is prepared, 7.5 parts of solution, which are added in oxygen sensitive material solution, prevents it
Reunite, 12h is stirred at room temperature under nitrogen protection atmosphere.
4. the preparation method of oxygen sensitive type multifunctional nano probe according to claim 3, which is characterized in that the oxygen
Gas sensitive material is pyrene, pyrene butyric acid, fluorine anthracene, cumarin, neighbour's Fei Luolin derivative and copper complex ([Cu (POP) (ptpm)]
BF4 one kind).
5. the preparation method of oxygen sensitive type multifunctional nano probe according to claim 1, which is characterized in that the step
In b, the photosensitizer of 200 part of 5 mg/mL is dissolved in 2 ~ 4 parts of step a acquired solution, be then added 2 ~ 4 parts of straight alcohols and 0 ~
4 parts of fluorocarbons.
6. according to claim 1 or the preparation method of the 5 oxygen sensitive type multifunctional nano probes, which is characterized in that described
Photosensitive agent material be hematoporphyrin derivative (HPD), dihematoporphyrin ethers (DHE) 5-ALA (5-ALA), m- tetrahydroxy
Phenyl chlorin (m-TH-PC), etioporphyrin (ETIO) tin (SnEtz), methylene blue (methylene blue) and methylene benzene are blue
(toluidine blue), benzene porphyrin (benzoporphyrin) derivative and lutelium texaphyrins(Lu-
Tex), benzoporphyrin derivative mono-acid (BPD-MA), phthalein blueness class (Phthalocyanines), get Ke Sa porphyrin
(Texaphyrins), N- lucid asparagus acyl group chlorin (Npe6), hypericin (hypercin), hematoporphyrin monomethyl ether
(HMME) and one of IR780.
7. according to claim 1 or the preparation method of the 5 oxygen sensitive type multifunctional nano probes, which is characterized in that described
Fluorocarbons be perfluoro butyl sulfonic acid fluoride (FC-4), full-fluorine octyl sulfuryl fluoride (FC-8), sulfluramid (FC-9), N- ethyl it is complete
Fluorine octyl sulfonamide ethyl alcohol (FC-10), perfluoro octyl sulfonic acid potassium (FC-95), perfluorobutyl potassium sulfonate (FC-98), perfluoro capryl
Sulfonamide (FC-99), perfluoro octyl sulfonic acid ammonium (FC-120), perfluoro capryl quaternary ammonium iodide (FC-134), perfluoro octyl sulfonic acid
Tetraethyl amine (FC-248), N- perfluoroalkyl group sulfonyl, propyl-triethoxysilicane (FC-922), perfluor alkane (FC-40), perfluor
Alkyl acrylate (FC-14), N- fluorobenzenesulfonimide, perfluoro hexyl sulfuryl fluoride, perfluorohexanesulfonic acid potassium, N- methyl perfluoro oneself
At least one of base sulfonamide, N- methyl perfluoro hexyl sulfoamido ethyl alcohol, perfluorodecalin, perfluamine.
8. the preparation method of oxygen sensitive type multifunctional nano probe according to claim 1, which is characterized in that the step
In c, the amido in the glutaraldehyde cross-linking external cladding material of 3.67 part of 25% concentration is added, removes impurity with deionized water afterwards for 24 hours
Nano-particle solution is obtained, freeze-drying forms powder.
9. a kind of oxygen sensitive type multifunctional nano probe, it is characterised in that -8 any the method preparation according to claim 1
It obtains.
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