CN108210931A - Nanometer diagnosis and treatment agent, preparation method and application - Google Patents
Nanometer diagnosis and treatment agent, preparation method and application Download PDFInfo
- Publication number
- CN108210931A CN108210931A CN201611159986.2A CN201611159986A CN108210931A CN 108210931 A CN108210931 A CN 108210931A CN 201611159986 A CN201611159986 A CN 201611159986A CN 108210931 A CN108210931 A CN 108210931A
- Authority
- CN
- China
- Prior art keywords
- hmon
- gox
- nano particle
- nanometer
- diagnosis
- 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
- 238000003745 diagnosis Methods 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 108010015776 Glucose oxidase Proteins 0.000 claims abstract description 57
- 239000004366 Glucose oxidase Substances 0.000 claims abstract description 57
- 229940116332 glucose oxidase Drugs 0.000 claims abstract description 57
- 235000019420 glucose oxidase Nutrition 0.000 claims abstract description 57
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 51
- 239000002105 nanoparticle Substances 0.000 claims abstract description 51
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 27
- 239000012876 carrier material Substances 0.000 claims abstract description 6
- 239000007787 solid Substances 0.000 claims description 31
- 238000003756 stirring Methods 0.000 claims description 27
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 239000000377 silicon dioxide Substances 0.000 claims description 15
- 229910052681 coesite Inorganic materials 0.000 claims description 14
- 229910052906 cristobalite Inorganic materials 0.000 claims description 14
- 229910052682 stishovite Inorganic materials 0.000 claims description 14
- 229910052905 tridymite Inorganic materials 0.000 claims description 14
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 13
- 229930064664 L-arginine Natural products 0.000 claims description 13
- 235000014852 L-arginine Nutrition 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 8
- 239000011148 porous material Substances 0.000 claims description 8
- 239000007822 coupling agent Substances 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 7
- 229910021529 ammonia Inorganic materials 0.000 claims description 6
- 239000002245 particle Substances 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- -1 amine salt Chemical class 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 4
- 230000008859 change Effects 0.000 claims description 4
- 239000002872 contrast media Substances 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 239000011780 sodium chloride Substances 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 101710128063 Carbohydrate oxidase Proteins 0.000 claims description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 2
- 235000009754 Vitis X bourquina Nutrition 0.000 claims description 2
- 235000012333 Vitis X labruscana Nutrition 0.000 claims description 2
- 240000006365 Vitis vinifera Species 0.000 claims description 2
- 235000014787 Vitis vinifera Nutrition 0.000 claims description 2
- 229910052710 silicon Inorganic materials 0.000 claims description 2
- 239000010703 silicon Substances 0.000 claims description 2
- 239000007789 gas Substances 0.000 abstract description 23
- 238000003384 imaging method Methods 0.000 abstract description 7
- 230000002195 synergetic effect Effects 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 239000004475 Arginine Substances 0.000 abstract 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 abstract 1
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 28
- 239000000243 solution Substances 0.000 description 21
- 238000002347 injection Methods 0.000 description 18
- 239000007924 injection Substances 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 13
- 239000003643 water by type Substances 0.000 description 13
- 230000000694 effects Effects 0.000 description 12
- 239000008103 glucose Substances 0.000 description 11
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical group OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 8
- WOWHHFRSBJGXCM-UHFFFAOYSA-M cetyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C WOWHHFRSBJGXCM-UHFFFAOYSA-M 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 5
- 235000013339 cereals Nutrition 0.000 description 5
- 238000013467 fragmentation Methods 0.000 description 5
- 238000006062 fragmentation reaction Methods 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000012901 Milli-Q water Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000000174 gluconic acid Substances 0.000 description 3
- 235000012208 gluconic acid Nutrition 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 235000003642 hunger Nutrition 0.000 description 3
- 229940124280 l-arginine Drugs 0.000 description 3
- 239000005543 nano-size silicon particle Substances 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 230000037351 starvation Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical class CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 239000006087 Silane Coupling Agent Substances 0.000 description 2
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical class CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000011717 athymic nude mouse Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 239000002086 nanomaterial Substances 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 210000001364 upper extremity Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000005211 alkyl trimethyl ammonium group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000010102 embolization Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- DCPMPXBYPZGNDC-UHFFFAOYSA-N hydron;methanediimine;chloride Chemical compound Cl.N=C=N DCPMPXBYPZGNDC-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 235000015096 spirit Nutrition 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- QQQSFSZALRVCSZ-UHFFFAOYSA-N triethoxysilane Chemical compound CCO[SiH](OCC)OCC QQQSFSZALRVCSZ-UHFFFAOYSA-N 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000004073 vulcanization Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Physics & Mathematics (AREA)
- Acoustics & Sound (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The present invention provides a kind of nanometer of diagnosis and treatment agent, is to load glucose oxidase (GOx) and L arginine simultaneously as carrier material by the use of hollow mesoporous organosilicon nano particle (HMON).The present invention also provides the preparation method and applications of this nanometer of diagnosis and treatment agent.The synergistic treatment that the ultrasonic imaging of tumour and the hungry treatment of tumour are combined with Gases for Treating can be achieved at the same time in this nanometer of diagnosis and treatment agent.Preparation process of the present invention is simple and convenient to operate, the equipment for not needing to complex and expensive, it is easy to accomplish industrialized production, therefore have a good application prospect in the Clinics and Practices field of tumour.
Description
Technical field
The present invention relates to medical nano material field, more particularly, to a kind of for treating the nano material of tumour, specifically
It is related to a kind of nanometer of diagnosis and treatment agent, preparation method and application.
Background technology
As a kind of alternative of chemotherapy of tumors, Gases for Treating is widely studied due to its very little side effect,
And it is considered as the therapy of a kind of " green ".In numerous gas mediums, nitric oxide (NO) is because of its special physiology
It is widely used in the Gases for Treating of tumour with pathological active.On the one hand, high concentration NO (>1 μM) mitochondria can be passed through
Cancer cell is directly killed with the nitrosification of DNA；On the other hand, NO can cooperate with enhancing photodynamic therapy and radiotherapy to control
Therapeutic effect.During NO Gases for Treating tumours, simultaneously can it is crucial that developing a kind of good NO donors of biocompatibility
Continuously discharge NO gases.L-arginine (L-Arg) has excellent bio-compatible as a kind of natural NO donors
Property, and under the catalysis of induction NO synzyme and hydrogen peroxide (H can be passed through2O2) decomposition sustained release NO gases.Therefore, when
L-Arg is transported to rich in H2O2Tumor microenvironment in when can generate a large amount of NO gases and for tumour Gases for Treating.
The hungry treatment of tumour mainly blocks the nutrition supply of tumor area and inhibits tumour growth by vascular embolization.
Since glucose is the main energy sources substance of tumor metabolic, by the metabolic response of glucose, i.e., in glucose oxidase
(GOx) under catalysis by convert glucose be gluconic acid and hydrogen peroxide (H2O2), so as to largely consume the glucose in tumour,
Play the effect of hungry treatment tumour.In addition, H caused by GOx degradation glucose2O2H in tumour cell can be dramatically increased2O2
Concentration, so as to cause tumour cell in high H2O2Death under concentration.High H2O2Concentration can be used for decomposing L-Arg and discharge big
Measure the Gases for Treating that NO gases are used for tumour, but high concentration H at present2O2It is not fully used.
At present, the hungry treatment of single Gases for Treating or tumour has many limitations, and curative effect is not notable enough.
Invention content
A kind of be simple and convenient to operate the purpose of the present invention is to provide preparation process nanometer diagnosis and treatment agent, preparation method
And application.
For achieving the above object, the present invention specifically provides a kind of nanometer of diagnosis and treatment agent, with hollow mesoporous organosilicon nanometer
Particle loads glucose oxidase and L-arginine simultaneously as carrier material, the carrier material.
In a specific embodiment of the invention, the hollow mesoporous organosilicon nano particle a diameter of 180~
240nm, cavity size are 120~180nm, and pore size is 3~4nm.
In a specific embodiment of the invention, the glucose oxidase (GOx) is grafted on hollow mesoporous organic
On nano silicon particles surface；
Preferably, glucose oxidase (GOx) covalence graft is on hollow mesoporous organosilicon nano grain surface.
In a specific embodiment of the invention, the L-arginine (L-Arg) is loaded in hollow mesoporous organosilicon
Nano particle cavity inside.
Preferably, glucose oxidase (GOx) is the glucose oxidase (GOx) of amino functional.
In a preferred technical solution of the invention, the present invention provides a kind of nanometer of diagnosis and treatment agent, with hollow mesoporous organic
Nano silicon particles (HMON) are used as a kind of carrier material, which loads glucose oxidase (GOx) and L- essence ammonia simultaneously
Sour (L-Arg), wherein glucose oxidase (GOx) are grafted on HMON surfaces, and L-arginine (L-Arg) is loaded in HMON cavitys
It is internal.
In the above-mentioned technical proposal of the present invention, the preparation method of the hollow mesoporous organosilicon nano particle (HMON)
Including：
A) solid SiO is prepared2Nano particle：Organic solvent, water and ammonia spirit are mixed, then add in orthosilicic acid tetrem
Ester (TEOS) simultaneously stirs, and solid SiO is made2Nano particle；
B) in solid SiO2Nano grain surface wraps up one layer of mesoporous organosilicon：Pore creating material and amine substance are added to water
In, then add in solid SiO prepared by above-mentioned steps a)2Nano particle simultaneously stirs, and adds in coupling agent and stirs, and obtains surface packet
It is wrapped with the solid SiO of one layer of mesoporous organosilicon2Nano particle；
C) solid SiO is removed2Nano particle：By the solid of surface one layer of mesoporous organosilicon of package of above-mentioned steps b) preparations
SiO2Nano particle is dispersed in Na2CO3In solution, stir 1-3 hours, obtain hollow mesoporous organosilicon nano particle (HMON).
Another aspect of the present invention is to provide the preparation method of a kind of nanometer of diagnosis and treatment agent, specifically comprise the following steps：
A) solid SiO is prepared2Nano particle：Organic solvent, water and ammonia spirit are mixed, then add in orthosilicic acid tetrem
Ester (TEOS) simultaneously stirs, and solid SiO is made2Nano particle；
B) in solid SiO2Nano grain surface wraps up one layer of mesoporous organosilicon：Pore creating material and amine substance are added to water
In, then add in solid SiO prepared by above-mentioned steps a)2Nano particle simultaneously stirs, and adds in coupling agent and stirs, and obtains surface packet
It is wrapped with the solid SiO of one layer of mesoporous organosilicon2Nano particle；
C) solid SiO is removed2Nano particle：Wrap up the reality of one layer of mesoporous organosilicon in surface prepared by above-mentioned steps b)
Heart SiO2Nano particle is dispersed in Na2CO3In solution, stir 1-3 hours, obtain hollow mesoporous organosilicon nano particle (HMON)；
D) glucose oxidase (GOx) is grafted to hollow mesoporous organosilicon nano particle (HMON) surface：By amine salt and Portugal
Grape carbohydrate oxidase (GOx) is dissolved in water, and is then added in coupling agent and is stirred to obtain solution for standby；By hollow mesoporous organosilicon nanometer
Particle (HMON), which is dispersed in water and adds in above-mentioned solution, to be continued stirring and obtains within 20-30 hour glucose oxidase (GOx) to be grafted
HMON (HMON-GOx) particle；
E) HMON-GOx loads L-Arg：HMON-GOx and L-Arg prepared by step d) is dispersed in water and stirs at room temperature
The HMON (L-Arg-HMON-GOx) for being loaded and (being transported altogether) GOx and L-Arg simultaneously in 20-30 hours is mixed, is centrifuged, freezing
It is dry, obtain nanometer diagnosis and treatment agent.
In a specific embodiment of the invention, the organic solvent described in step a) is alcohols, ketone, ethers,
Preferred alcohol, methanol, propyl alcohol, glycerine.
In a specific embodiment of the invention, the pore creating material described in step b) is pore-creating commonly used in the art
Agent, preferably hexadecyltrimethylammonium chloride (CTAC).
In a specific embodiment of the invention, amine substance is triethanolamine (TEA) in step b).
In a specific embodiment of the invention, coupling agent is silane coupling agent in step b), preferably bis- [3- (three
Triethoxysilyl) propyl] tetrasulfide (BTES).
In a specific embodiment of the invention, amine salt is 1- (3- dimethylamino-propyls) -3- ethyls in step d)
Carbodiimide hydrochloride (EDC), n-hydroxysuccinimide (NHS) or combination；It is preferred that combination, matches
Than being 1：1~1：2.
In a specific embodiment of the invention, coupling agent is silane coupling agent, preferably 3- aminopropyls in step d)
Triethoxysilane (APTES).
In a specific embodiment of the invention, used water is ultra-pure water.
In a specific embodiment of the invention, further included after wherein step c)：It is more using NaCl methanol solutions
Secondary extraction removes remaining pore creating material in hollow mesoporous organosilicon nano particle (HMON).
Heretofore described room temperature refers to the indoor temperature in laboratory, and range is at 20-25 degrees Celsius.
In a specific technical solution of the invention, specifically comprise the following steps：
A) solid SiO is prepared2Nano particle：By 74mL ethyl alcohol, 10mL ultra-pure waters and 3.14mL ammonia in 30 DEG C of water-bath
Aqueous solution is mixed and stirred for 5 minutes, is then quickly added into 6mL tetraethyl orthosilicates (TEOS) and is continued stirring and obtains reality in 1 hour
Heart SiO2Nano particle centrifuges, and is dispersed in 60mL ultra-pure waters after ethyl alcohol washing, for use；
B) in solid SiO2Nano grain surface wraps up one layer of mesoporous organosilicon：2g hexadecyltrimethylammonium chlorides
(CTAC) it is added in 90mL ultra-pure waters and stirs 1.5 hours with 0.04g triethanolamines (TEA), then add in the above-mentioned systems of 30mL
Standby solid SiO2Nanoparticles solution is simultaneously again stirring for 1.5 hours；Then bis- [3- (the triethoxy first silicon of 1.8mL are added dropwise
Alkyl) propyl] tetrasulfide (BTES) and being stirred under 80 ° obtains being coated with the solid of one layer of mesoporous organosilicon for 1 hour
SiO2Nano particle centrifuges, and is dispersed in 30mL ultra-pure waters after ethyl alcohol washing, for use；
C) solid SiO is removed2Nano particle：The surface of above-mentioned preparation is wrapped up to the solid SiO of one layer of mesoporous organosilicon2It receives
Rice grain is dispersed in the Na of 0.6 mol/L2CO3It stirs 1 hour, centrifuges in solution and at 80 DEG C, after milli-Q water
Obtain HMON；
D) remaining CTAC in removal HMON is repeatedly extracted using NaCl methanol solutions；
E) the GOx covalence grafts of amino functional are to HMON surfaces：38mg 1- (3- dimethylamino-propyls) -3- ethyl carbon
Diimmonium salt hydrochlorate (EDC), 57mg n-hydroxysuccinimides (NHS) and a certain amount of GOx are dissolved in 6
In mL ultra-pure waters, then add in 45 μ L 3- aminopropyl triethoxysilanes (APTES) and at room temperature stirring it is 8 small
When, 20mg HMON, which are dispersed in 4mL ultra-pure waters and add in above-mentioned solution, continues the HMON that stirring obtains GOx grafting for 24 hours
(HMON-GOx) particle centrifuges, and is dispersed in 5mL ultra-pure waters after milli-Q water, for use.
F) HMON-GOx loads L-Arg：20mg HMON-GOx and 200mg L-Arg be dispersed in 10mL ultra-pure waters and
The HMON (L-Arg-HMON-GOx) for being loaded and (being transported altogether) GOx and L-Arg simultaneously in 24 hours, centrifugation point are stirred at room temperature
From freeze-drying.
Third aspect present invention is to provide application of the nanometer diagnosis and treatment agent in the preparation for preparing treatment tumour, together
When the diagnosis and treatment agent also be used as acoustic contrast agent.
Preferably, the treatment of the tumour is simultaneously using hungry treatment and Gases for Treating.
The invention has the advantages that：The nanometer diagnosis and treatment agent prepared by preparation method of the present invention can be achieved at the same time swollen
The synergistic treatment that the ultrasonic imaging of knurl and the hungry treatment of tumour are combined with Gases for Treating, thus tumour diagnosis with controlling
Treatment field will have a good application prospect.Meanwhile preparation process of the invention is simple and convenient to operate, and does not need to complex and expensive
Equipment, it is easy to accomplish industrialized production.
Description of the drawings
Fig. 1 is that the route map of hollow mesoporous organosilicon nano particle (HMON) and corresponding TEM figures are synthesized in embodiment 1；
Fig. 2 is that synthesis HMON loads (transport altogether) simultaneously the route map of GOx and L-Arg and corresponding TEM in embodiment 2
Figure；
Fig. 3 is fragmentation effect of evaluation starvation in the embodiment 3/gas associating treatment to U87MG tumour cells；
Fig. 4 is that HMON-GOx is evaluated in embodiment 4 to U87MG tumours blood oxygen saturation and H2O2The influence of content；
Inhibition of the starvation/gas associating treatment to U87MG tumour growths is evaluated in Fig. 5 embodiments 5.
Specific embodiment
With reference to specific embodiment, the present invention is further explained.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.
Embodiment 1 synthesizes hollow mesoporous organosilicon nano particle (HMON)
74mL ethyl alcohol, 10mL ultra-pure waters and 3.14mL ammonia spirits are mixed and stirred for 5 points first in 30 DEG C of water-bath
Clock is then quickly added into 6mL tetraethyl orthosilicates (TEOS) and continues stirring 1 hour, obtains solid SiO2Nano particle.By 2g
CTAC and 0.04g triethanolamines (TEA) are added in 90mL ultra-pure waters and stir 1.5 hours, add in the reality of the above-mentioned preparations of 30mL
Heart SiO2Nanoparticles solution stirs 1.5 hours.To above-mentioned solution be added dropwise 1.8mL BTES and at 80 DEG C stirring it is 1 small
When obtain surface wrap up one layer of mesoporous organosilicon solid SiO2Nano particle.It is finally that one layer prepared of surface package is mesoporous
The solid SiO of organosilicon2Nano particle is dispersed in the Na of 0.6 mol/L2CO3It stirs 1 hour, centrifuges in solution and at 80 DEG C
It detaches, HMON is obtained after milli-Q water.Remaining CTAC then repeatedly extracts removal using NaCl methanol solutions in HMON, obtains
Hollow mesoporous organosilicon nano particle (HMON).
A diameter of 180~240nm of the hollow mesoporous organosilicon nano particle, cavity size be 120~180nm, hole
Size is 3~4nm.
Route map and the corresponding TEM figures for synthesizing hollow mesoporous organosilicon nano particle (HMON) are as shown in Figure 1.
(a) represents to synthesize the route map of hollow mesoporous organosilicon nano particle (HMON) in Fig. 1, and wherein CTAC represents 16
Alkyl trimethyl ammonium chloride, TEA represent triethanolamine, and BTES represents bis- [3- (triethoxysilyl) propyl] four vulcanization
Object, Na2CO3Represent sodium carbonate；(b), (c), (d) represent solid SiO respectively2Nano particle (SiO2), be coated with one layer of Jie
The solid SiO of hole organosilicon2Nano particle (SiO2@MON), the TEM of hollow mesoporous organosilicon nano particle (HMON) figure.
Embodiment 2 synthesizes L-Arg-HMON-GOx
First 38mg EDC, 57mg NHS and a certain amount of GOx are dissolved in 6mL ultra-pure waters, and add in 45 μ L APTES
After be stirred at room temperature 8 hours and obtain amidized GOx.Then 20mg HMON are dispersed in 4mL ultra-pure waters and added in above-mentioned
Solution continues HMON (HMON-GOx) particle that stirring obtains GOx grafting for 24 hours.Finally by 20mg HMON-GOx and 200mg
L-Arg is dispersed in 10mL ultra-pure waters and (stirring) is stirred at room temperature 24 hours, is transported GOx's and L-Arg altogether
HMON (L-Arg-HMON-GOx) multifunctional nano diagnosis and treatment agent.Synthesis HMON loads (transport altogether) simultaneously GOx and L-Arg route maps
It is as shown in Figure 2 with TEM figures.
(a) represents that synthesis HMON loads (transport altogether) simultaneously GOx and L-Arg route maps in Fig. 2, and wherein APTES represents 3-
Aminopropyl triethoxysilane, NHS represent n-hydroxysuccinimide, and EDC represents 1- (3- dimethylamino-propyls) -3- ethyl carbon
Diimmonium salt hydrochlorate, GOx represent glucose oxidase, and L-Arg represents L-arginine；(b), (c), (d) represent hollow Jie respectively
Hole organic silicon nano particle (HMON), GOx grafting HMON (HMON-GOx) while the HMON for loading and (transporting altogether) GOx and L-Arg
(L-Arg-HMON-GOx) TEM figures.
The weight proportion of glucose oxidase and L-arginine is 1：1-1：2, preferably 1：1.3.
Embodiment 3
Using the mtt assay of standard, starvation/influence of the Gases for Treating synergistic therapeutic action to U87MG cell survival rates is evaluated.
U87MG cells are with every hole 1 × 104Density is inoculated into 96 orifice plates, is placed in 37 DEG C, 5%CO2Under the conditions of cultivate for 24 hours.Then, it inhales
Go out the old culture medium in 96 orifice plates, be separately added into containing 200 μ g/mL HMON-GOx, HMON-L-Arg and L-Arg-HMON-GOx
Sugar-free DMEM culture mediums (no glucose) and have sugared (100 μ g/mL glucose) DMEM culture mediums.Continue culture for 24 hours
Afterwards, the old culture medium in 96 orifice plates is sucked out, the culture medium solution of 100 μ L MTT is added in each hole, and (0.8mg/mL continues to train
Support 4h.The residual media in 96 orifice plates is sucked out, 100 μ L DMSO solutions are added in each hole, after jiggling, in Bio-
OD value (Detection wavelength 570nm) of the detection per hole in the type microplate reader of TelEL × 800 calculates cell survival rate with equation below.
Cell survival rate (cell viability) (%)=(the OD570 values of sample/blank OD570 values) × 100%, experimental result is shown in
Fig. 3.
As shown in figure 3, in sugar-free DMEM culture mediums (no glucose), L-Arg-HMON-GOx can be significantly reduced
U87MG cell survival rates (cell viability)；And the fragmentation effect to cell of L-Arg-HMON-GOx is significantly better than
HMON-GOx, HMON-L-Arg are to the fragmentation effect of cell；In having sugared (100 μ g/mL glucose) DMEM culture mediums, L-
Arg-HMON-GOx can significantly reduce U87MG cell survival rates (cell viability), and pair of L-Arg-HMON-GOx
The fragmentation effect of cell is significantly better than the fragmentation effect of HMON-GOx, HMON-L-Arg to cell.
Embodiment 4
All experimental implementations according to the clinical center animal health of National Institutes of Health and use the committee
By animal use and health care system.Female athymic nude mice (six weeks, 20-25g), nude mice foreleg be subcutaneously injected 2 ×
106The PBS solution of U87MG tumour cells establishes mouse tumor model.When gross tumor volume reaches 60mm3When, by 150 μ L 10mg/mL
The PBS solution of HMON-GOx by way of intratumor injection, is directly injected into U87MG tumours, utilizes toy photoacoustic imaging system
" Oxyhemo " pattern of (VisualSonics Vevo LAZR system) detects the blood oxygen saturation of tumor area
(average sO2(%)), variation of the observation tumour blood oxygen saturation after HMON-GOx injections in 2h.In addition, utilize sulphur
The H of tumor area after sour titanium detection HMON-GOx injections 4h2O2Concentration (H2O2concentration).Experimental result is shown in Fig. 4.
(a) (b) (c) represents tumour the blood oxygen of 2h is satisfied after 1h and injection before HMON-GOx injections, after injection respectively in Fig. 4
With concentration schematic diagram, (d) represents blood oxygen saturation (average sO2(%)) variation after HMON-GOx injections in 2h
Figure, (e) represent the H of tumor area after HMON-GOx injections 4h2O2Concentration (H2O2Concentration) change；It is as shown in figure 4, swollen
Knurl blood oxygen saturation (average sO2(%)) it can be significantly reduced in 2h, while HMON-GOx is noted after HMON-GOx injections
Enter the H of tumor area after 4h2O2Concentration (H2O2Concentration it) significantly improves.
Embodiment 5
Female athymic nude mice (six weeks, 20-25g) is subcutaneously injected 2 × 10 in nude mice foreleg6U87MG tumour cells
PBS solution establishes mouse tumor model.When gross tumor volume reaches 60mm3When, carry out Experiment on therapy.U87MG tumor-bearing mices divide at random
It is five groups：(1) blank group (control)；(2) HMON groups are injected；(3) HMON-L-Arg groups are injected；(4) HMON-GOx groups are injected；
(5) L-Arg-HMON-GOx groups are injected.Vernier caliper measurement gross tumor volume is every other day used, and according to formula V=AB2/ 2 calculate
Gross tumor volume (relative volume), wherein A are the major diameters of tumour, and B is the minor axis (mm) of tumour.Each measurement result is equal
It is normalized, and observe the life cycle (survival) of every group of mouse by the starting tumor volume of before processing.Experimental result
See Fig. 5.
(f) represents the situation of change of different treatment group tumors volumes (relative volume) (Day) at any time in Fig. 5,
As shown in figure 5, injection L-Arg-HMON-GOx groups can significantly inhibit the growth of tumour, the effect of L-Arg-HMON-GOx groups is injected
Fruit is significantly better than injection HMON-GOx groups, injection HMON-L-Arg groups, injection HMON groups and blank group (control)；(g) table
Show the situation of change of the life cycle (survival) of different treatment group mouse (Day) at any time, as shown in figure 5, injection L-
Arg-HMON-GOx groups significantly improve the life cycle of mouse, and the significant effect of injection L-Arg-HMON-GOx groups is better than injection
HMON-GOx groups, injection HMON-L-Arg groups, injection HMON groups and blank group (control).
The ultrasonic imaging of tumour can be achieved at the same time in diagnosis and treatment agent of the present invention and the hungry treatment of tumour is controlled with gas
Treat the synergistic treatment being combined.
In the present invention, the HMON has good biocompatibility, cell survival rate after being co-cultured 24 hours with cell
More than 95%；The HMON has good biodegradability, degradable complete in 30 days.The HMON can be used as super
Sound contrast agent is used for tumour ultrasonic imaging.
The GOx of HMON surfaces covalence graft for gluconic acid and can have intracellular convert glucose cytotoxic
Hydrogen peroxide (H2O2), so as to largely consume intracellular energy source and nutriment, play the effect of hungry treatment tumour.
L-Arg is in acidic environment caused by GOx and H2O2Lower decomposable asymmetric choice net generates a large amount of nitric oxide gas, so as to real
The Gases for Treating of existing tumour.
First, HMON has good biocompatibility and biodegradability, and HMON can be used as acoustic contrast agent
For the ultrasonic imaging of tumour.Secondly, intracellular convert glucose for gluconic acid and is had cytotoxic using GOx
Hydrogen peroxide so as to largely consume intracellular energy source and nutriment, plays the effect of hungry treatment tumour.The opposing party
Face efficient-decomposition L-arginine and can generate a large amount of nitric oxide gas using acidic environment caused by GOx and hydrogen peroxide,
So as to fulfill the Gases for Treating of tumour.
The invention has the advantages that：The nanometer diagnosis and treatment agent prepared by preparation method of the present invention can be achieved at the same time swollen
The synergistic treatment that the ultrasonic imaging of knurl and the hungry treatment of tumour are combined with Gases for Treating, thus tumour diagnosis with controlling
Treatment field will have a good application prospect.Meanwhile preparation process of the invention is simple and convenient to operate, and does not need to complex and expensive
Equipment, it is easy to accomplish industrialized production.
It is it is necessary to described herein finally：Above example is served only for making technical scheme of the present invention further detailed
Ground explanation, it is impossible to be interpreted as limiting the scope of the invention, those skilled in the art's the above according to the present invention
Some the nonessential modifications and adaptations made all belong to the scope of protection of the present invention.
Claims (10)
1. a kind of nanometer of diagnosis and treatment agent, it is characterised in that：Using hollow mesoporous organosilicon nano particle as carrier material, the carrier material
Material loads glucose oxidase and L-arginine simultaneously.
2. according to claim 1 nanometer of diagnosis and treatment agent, which is characterized in that the diameter of the hollow mesoporous organosilicon nano particle
For 180~240nm, cavity size is 120~180nm, and pore size is 3~4nm.
3. according to claim 1 nanometer of diagnosis and treatment agent, which is characterized in that the glucose oxidase (GOx) is grafted on the sky
On the surface of heart mesoporous organosilicon nano particle.
4. according to claim 1 nanometer of diagnosis and treatment agent, which is characterized in that it is hollow that the L-arginine (L-Arg) is loaded in this
The cavity inside of mesoporous organosilicon nano particle.
5. according to claim 1 nanometer of diagnosis and treatment agent, which is characterized in that the glucose oxidase (GOx) is amino functional
The glucose oxidase (GOx) of change.
6. the preparation method of claim 1-5 any one of them nanometer diagnosis and treatment agent, which is characterized in that specifically include following step
Suddenly：
A) solid silica (SiO is prepared2) nano particle：Organic solvent, water and ammonia spirit are mixed, then add in former silicon
Sour tetra-ethyl ester (TEOS) is simultaneously stirred, and obtains solid SiO2Nano particle；
B) in solid SiO2Nano grain surface wraps up one layer of mesoporous organosilicon：Pore creating material and amine substance are added to the water, so
Solid SiO prepared by above-mentioned steps a) is added in afterwards2Nano particle simultaneously stirs, and adds in coupling agent and stirs, is coated with
The solid SiO of one layer of mesoporous organosilicon2Nano particle；
C) solid SiO is removed2Nano particle：The solid of one layer of mesoporous organosilicon is coated with by prepared by above-mentioned steps b)
SiO2Nano particle is dispersed in Na2CO3In solution, stir 1-3 hours, obtain hollow mesoporous organosilicon nano particle (HMON)；
D) glucose oxidase (GOx) is grafted to the surface of hollow mesoporous organosilicon nano particle (HMON)：By amine salt and grape
Carbohydrate oxidase (GOx) is dissolved in water, and is then added in coupling agent and is stirred to obtain solution for standby；By hollow mesoporous organosilicon nanometer
Grain (HMON), which is dispersed in water and adds in above-mentioned solution and continue stirring, obtains what glucose oxidase (GOx) was grafted for 20-30 hour
HMON (HMON-GOx) particle；
E) HMON-GOx loads L-Arg：HMON-GOx and L-Arg prepared by step d) is dispersed in water and is stirred at room temperature
The HMON (L-Arg-HMON-GOx) for being loaded GOx and L-Arg simultaneously in 20-30 hours is centrifuged, and is freeze-dried, and is obtained
Nanometer diagnosis and treatment agent.
7. the preparation method of according to claim 6 nanometer of diagnosis and treatment agent, which is characterized in that further included after step c)：Profit
Remaining pore creating material in the hollow mesoporous organosilicon nano particle (HMON) of removal is repeatedly extracted with NaCl methanol solutions.
8. according to application of the claim 1-5 any one of them nanometer diagnosis and treatment agent in the preparation for preparing treatment tumour.
9. application according to claim 8, which is characterized in that the nanometer diagnosis and treatment agent is also used as acoustic contrast agent simultaneously.
10. application according to claim 8, which is characterized in that the treatment is controls using hungry treatment and gas simultaneously
It treats.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611159986.2A CN108210931A (en) | 2016-12-15 | 2016-12-15 | Nanometer diagnosis and treatment agent, preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611159986.2A CN108210931A (en) | 2016-12-15 | 2016-12-15 | Nanometer diagnosis and treatment agent, preparation method and application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108210931A true CN108210931A (en) | 2018-06-29 |
Family
ID=62650432
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611159986.2A Pending CN108210931A (en) | 2016-12-15 | 2016-12-15 | Nanometer diagnosis and treatment agent, preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108210931A (en) |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108926709A (en) * | 2018-07-02 | 2018-12-04 | 深圳大学 | A kind of nanometer cooperative therapeutic agent and the preparation method and application thereof |
| CN110201167A (en) * | 2019-07-03 | 2019-09-06 | 西南大学 | Illumination discharges the preparation method of the load enzyme bismuth selenide nanoparticle of oxygen |
| CN110403916A (en) * | 2019-07-31 | 2019-11-05 | 深圳大学 | A kind of nanometer of therapeutic agent and the preparation method and application thereof |
| CN110680926A (en) * | 2019-09-09 | 2020-01-14 | 深圳大学 | Nano diagnosis and treatment agent and preparation method and application thereof |
| CN112535739A (en) * | 2020-12-08 | 2021-03-23 | 中山大学 | Nano-particles for improving gene transfection efficiency based on tumor microenvironment, and preparation method and application thereof |
| CN112915213A (en) * | 2021-02-02 | 2021-06-08 | 复旦大学附属眼耳鼻喉科医院 | Response type NO nano-drug, preparation method and application thereof |
| CN113384716A (en) * | 2021-06-16 | 2021-09-14 | 南京诺源医疗器械有限公司 | fluorescence/PET bimodal imaging probe and preparation method and application thereof |
| CN113813402A (en) * | 2021-09-30 | 2021-12-21 | 中国药科大学 | Preparation method and application of nanogel with hunger combined gas therapy anti-tumor function |
| CN114366722A (en) * | 2022-01-11 | 2022-04-19 | 河北工业大学 | Polyphenol-mediated multifunctional bionic metal-organic framework mixed structure and preparation and application thereof |
| CN114652819A (en) * | 2022-03-21 | 2022-06-24 | 滨州医学院 | Degradable multifunctional nano material for targeting tumor microenvironment and preparation method thereof |
| CN115350162A (en) * | 2022-08-30 | 2022-11-18 | 辽宁大学 | Bionic mesoporous organic silicon nano drug-loading system and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1326785A (en) * | 2000-06-01 | 2001-12-19 | 孔庆忠 | Anti-cancer medicine composition |
-
2016
- 2016-12-15 CN CN201611159986.2A patent/CN108210931A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1326785A (en) * | 2000-06-01 | 2001-12-19 | 孔庆忠 | Anti-cancer medicine composition |
Non-Patent Citations (1)
| Title |
|---|
| WENPEI FAN ET AL.: ""Glucose-Responsive Sequential Generation of Hydrogen Peroxide andNitric Oxide for Synergistic Cancer Starving-Like/Gas Therapy"", 《ANGEW. CHEM. INT. ED.》 * |
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108926709B (en) * | 2018-07-02 | 2021-07-13 | 深圳大学 | Nano-synergistic therapeutic agent and preparation method and application thereof |
| CN108926709A (en) * | 2018-07-02 | 2018-12-04 | 深圳大学 | A kind of nanometer cooperative therapeutic agent and the preparation method and application thereof |
| CN110201167A (en) * | 2019-07-03 | 2019-09-06 | 西南大学 | Illumination discharges the preparation method of the load enzyme bismuth selenide nanoparticle of oxygen |
| CN110403916A (en) * | 2019-07-31 | 2019-11-05 | 深圳大学 | A kind of nanometer of therapeutic agent and the preparation method and application thereof |
| CN110403916B (en) * | 2019-07-31 | 2021-08-10 | 深圳大学 | Nano therapeutic agent and preparation method and application thereof |
| CN110680926B (en) * | 2019-09-09 | 2023-01-17 | 深圳大学 | Nano diagnosis and treatment agent and preparation method and application thereof |
| CN110680926A (en) * | 2019-09-09 | 2020-01-14 | 深圳大学 | Nano diagnosis and treatment agent and preparation method and application thereof |
| CN112535739A (en) * | 2020-12-08 | 2021-03-23 | 中山大学 | Nano-particles for improving gene transfection efficiency based on tumor microenvironment, and preparation method and application thereof |
| CN112915213A (en) * | 2021-02-02 | 2021-06-08 | 复旦大学附属眼耳鼻喉科医院 | Response type NO nano-drug, preparation method and application thereof |
| CN113384716A (en) * | 2021-06-16 | 2021-09-14 | 南京诺源医疗器械有限公司 | fluorescence/PET bimodal imaging probe and preparation method and application thereof |
| CN113813402A (en) * | 2021-09-30 | 2021-12-21 | 中国药科大学 | Preparation method and application of nanogel with hunger combined gas therapy anti-tumor function |
| CN113813402B (en) * | 2021-09-30 | 2024-02-27 | 中国药科大学 | Preparation method and application of nanogel with anti-tumor function of hunger combined gas therapy |
| CN114366722A (en) * | 2022-01-11 | 2022-04-19 | 河北工业大学 | Polyphenol-mediated multifunctional bionic metal-organic framework mixed structure and preparation and application thereof |
| CN114652819A (en) * | 2022-03-21 | 2022-06-24 | 滨州医学院 | Degradable multifunctional nano material for targeting tumor microenvironment and preparation method thereof |
| CN114652819B (en) * | 2022-03-21 | 2024-06-21 | 滨州医学院 | Multifunctional nano material capable of degrading targeted tumor microenvironment and preparation method thereof |
| CN115350162A (en) * | 2022-08-30 | 2022-11-18 | 辽宁大学 | Bionic mesoporous organic silicon nano drug-loading system and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108210931A (en) | Nanometer diagnosis and treatment agent, preparation method and application | |
| Ding et al. | A multimodal Metal-Organic framework based on unsaturated metal site for enhancing antitumor cytotoxicity through Chemo-Photodynamic therapy | |
| Zhao et al. | An energy‐storing DNA‐based nanocomplex for laser‐free photodynamic therapy | |
| Zhang et al. | Cyanobacteria-based near-infrared light-excited self-supplying oxygen system for enhanced photodynamic therapy of hypoxic tumors | |
| CN110743012A (en) | Preparation method and application of glucose oxidase modified mesoporous manganese dioxide pharmaceutical composition | |
| CN108042810B (en) | Acid-response hydrogen release nano-medicament and preparation method thereof | |
| Zhang et al. | An injectable hydrogel co-loading with cyanobacteria and upconversion nanoparticles for enhanced photodynamic tumor therapy | |
| Li et al. | A smart nanoplatform for synergistic starvation, hypoxia-active prodrug treatment and photothermal therapy mediated by near-infrared-II light | |
| Zhang et al. | Intelligent protein-coated bismuth sulfide and manganese oxide nanocomposites obtained by biomineralization for multimodal imaging-guided enhanced tumor therapy | |
| Zuo et al. | Mitochondria-targeted mesoporous titanium dioxide nanoplatform for synergistic nitric oxide gas-sonodynamic therapy of breast cancer | |
| CN113694023B (en) | Oxidation response type nano micelle and preparation method and application thereof | |
| Jia et al. | Boosting the tumor photothermal therapy with hollow CoSnSx-based injectable hydrogel via the sonodynamic and dual-gas therapy | |
| Liao et al. | A novel platform of MOF for sonodynamic therapy advanced therapies | |
| CN115317607B (en) | Mono-atom iron doped graphite phase carbon nitride nanocomposite, preparation method and application thereof | |
| CN111840570A (en) | Preparation method of nano-particles of sericin combined with photosensitizer | |
| CN112972423A (en) | Cascade reaction-based nano enzyme and chemotherapeutic drug co-loaded bionic nano drug carrier and preparation method and application thereof | |
| Zhang et al. | Tumor microenvironment-responsive degradable silica nanoparticles: design principles and precision theranostic applications | |
| Liu et al. | Photothermal-accelerated urease-powered human serum albumin nanomotor for rapid and efficient photothermal and photodynamic cancer combination therapy | |
| CN109674764A (en) | A kind of antitumor magnetic drug-carrying hybridized nanometer capsule and preparation method thereof | |
| CN113577306A (en) | Preparation of double-targeting pH stimulus-responsive nano particles and application of nano particles in tumor diagnosis and treatment | |
| CN113350524A (en) | Iron-blocking magnetic nano-drug responding to tumor microenvironment as well as preparation method and application thereof | |
| Chen et al. | Iron‐Rich Semiconducting Polymer Dots for the Combination of Ferroptosis–Starvation and Phototherapeutic Cancer Therapy | |
| CN105056239B (en) | The composite material and its preparation of functional mesoporous silicon dioxide carried drug and siRNA and the application in preparing anticancer drug | |
| CN104353076B (en) | Hypoxia dependent form X-ray kinetics nanometric photosensitizer and preparation method and application | |
| CN113827724B (en) | Drug-loaded Prussian blue @ manganese fibrin composite gel, and preparation method and application thereof |
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 | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20180629 |