CN110448540A - Hydrogen sulfide intelligent response for the chemotherapy of colon cancer, the nano material of thermotherapy and its preparation method and application - Google Patents
Hydrogen sulfide intelligent response for the chemotherapy of colon cancer, the nano material of thermotherapy and its preparation method and application Download PDFInfo
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- CN110448540A CN110448540A CN201910570568.XA CN201910570568A CN110448540A CN 110448540 A CN110448540 A CN 110448540A CN 201910570568 A CN201910570568 A CN 201910570568A CN 110448540 A CN110448540 A CN 110448540A
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- colon cancer
- chemotherapy
- nano material
- hydrogen sulfide
- thermotherapy
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- 208000029742 colonic neoplasm Diseases 0.000 title claims abstract description 61
- 206010009944 Colon cancer Diseases 0.000 title claims abstract description 47
- 239000002086 nanomaterial Substances 0.000 title claims abstract description 41
- 238000002512 chemotherapy Methods 0.000 title claims abstract description 38
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 229910000037 hydrogen sulfide Inorganic materials 0.000 title claims abstract description 35
- 230000004044 response Effects 0.000 title claims abstract description 29
- 238000000015 thermotherapy Methods 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 50
- 229910052802 copper Inorganic materials 0.000 claims abstract description 47
- 239000010949 copper Substances 0.000 claims abstract description 47
- 239000010953 base metal Substances 0.000 claims abstract description 44
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 40
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 35
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 35
- 239000003814 drug Substances 0.000 claims abstract description 33
- OMZSGWSJDCOLKM-UHFFFAOYSA-N copper(II) sulfide Chemical compound [S-2].[Cu+2] OMZSGWSJDCOLKM-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000007626 photothermal therapy Methods 0.000 claims abstract description 8
- 238000003745 diagnosis Methods 0.000 claims abstract description 6
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 claims description 68
- 239000000463 material Substances 0.000 claims description 51
- QMKYBPDZANOJGF-UHFFFAOYSA-N benzene-1,3,5-tricarboxylic acid Chemical compound OC(=O)C1=CC(C(O)=O)=CC(C(O)=O)=C1 QMKYBPDZANOJGF-UHFFFAOYSA-N 0.000 claims description 44
- 229940109262 curcumin Drugs 0.000 claims description 34
- 235000012754 curcumin Nutrition 0.000 claims description 34
- 239000004148 curcumin Substances 0.000 claims description 34
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 claims description 34
- 239000013384 organic framework Substances 0.000 claims description 27
- 230000004048 modification Effects 0.000 claims description 24
- 238000012986 modification Methods 0.000 claims description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- 238000004806 packaging method and process Methods 0.000 claims description 17
- 238000010521 absorption reaction Methods 0.000 claims description 15
- 238000003384 imaging method Methods 0.000 claims description 15
- 206010028980 Neoplasm Diseases 0.000 claims description 13
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 13
- 238000005406 washing Methods 0.000 claims description 11
- 235000019441 ethanol Nutrition 0.000 claims description 7
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 229960002949 fluorouracil Drugs 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 208000005016 Intestinal Neoplasms Diseases 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 229940009456 adriamycin Drugs 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 150000001336 alkenes Chemical class 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 claims 1
- 210000001072 colon Anatomy 0.000 claims 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 6
- 230000001225 therapeutic effect Effects 0.000 abstract description 3
- 238000005253 cladding Methods 0.000 abstract 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 32
- 239000000243 solution Substances 0.000 description 19
- 230000000694 effects Effects 0.000 description 14
- 239000003560 cancer drug Substances 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 239000012621 metal-organic framework Substances 0.000 description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 239000005864 Sulphur Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 238000010253 intravenous injection Methods 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 2
- UJMDYLWCYJJYMO-UHFFFAOYSA-N benzene-1,2,3-tricarboxylic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=C1C(O)=O UJMDYLWCYJJYMO-UHFFFAOYSA-N 0.000 description 2
- 229910001431 copper ion Inorganic materials 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 201000002313 intestinal cancer Diseases 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 238000010895 photoacoustic effect Methods 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000002539 nanocarrier Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000001931 thermography Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
-
- 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
- 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
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- 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
- A61K9/5138—Organic macromolecular compounds; Dendrimers obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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Abstract
The present invention relates to a kind of hydrogen sulfide intelligent responses for the chemotherapy of colon cancer, the nano material of thermotherapy and its preparation method and application, the nano material is the copper base metal organic backbone nano material of polyvinyl pyrrolidon modified package colon cancer chemotherapy medicament, copper sulfide can be generated in conjunction with the Endogenous Hydrogen Sulfide at colon tumor position, while releasing chemotherapeutics;The copper base metal organic backbone nano material of package colon cancer chemotherapy medicament is synthesized when preparation first, then cladding polyvinylpyrrolidone improves water solubility on surface.Compared with prior art, nano material of the invention can be with colon cancer Endogenous Hydrogen Sulfide intelligent response, colon cancer chemotherapy medicament is discharged while triggering photo-thermal therapy, the nano material is in colon tumor site specific intelligent response, in conjunction with chemotherapy and thermotherapy, preparation method is easy, therapeutic effect is obvious, provides a kind of new diagnosis and treatment reagent for the efficient treatment of colon cancer.
Description
Technical field
The invention belongs to technical field of nano material, be related to a kind of hydrogen sulfide intelligent response for colon cancer chemotherapy,
Nano material of thermotherapy and its preparation method and application.
Background technique
The total sick hair rate of colon cancer occupies global third position, but its lethality is but in second, is acknowledged as the whole world
One of most common malignant tumour.Therefore, the early diagnosis of colon cancer is realized, and improves the therapeutic effect of colon cancer that there is weight
The clinical meaning wanted.Curcumin is a kind of natural chemical with high degree of biocompatibility and biodegradable, to people
The health of body has extensive therapeutic effect, and simple curcumin cannot be complete due to the bioavilability of its high hydrophobicity and difference
Body administration.Therefore, it is highly desirable to develop a kind of simple and efficient way, curcumin can be integrated in nano-carrier, and
Realize fixed point administration on demand.Metal organic framework is a kind of emerging mixed crystal porous material.It has macroporosity, high
The features such as surface area, adjustable shape and aperture and controlled surface, becomes drug molecule conveying and the powerful of control release is put down
Platform.Therefore, we invent a kind of metal organic framework nano material for wrapping up curcumin.
Compared with the diagnoses and treatment method of traditional colon cancer, near-infrared reagent have diagnosis and treatment integration, Noninvasive,
Many advantages, such as Small side effects, but this kind of reagent is there are a great defect, is exactly to be easy quilt after intravenously administrable
Normal tissue retains, also can normal tissue generation wound when causing normal tissue to generate video signal interference, while treating
Wound.Therefore, reduce the damage of normal tissue in order to avoid imaging signal interference, while when photo-thermal therapy, exploitation is only swollen
Tumor position, which could generate optoacoustic image and the intelligent near-infrared reagent of photo-thermal therapy effect, has important clinical meaning.
Summary of the invention
It is an object of the present invention to overcome the above-mentioned drawbacks of the prior art and provide a kind of hydrogen sulfide intelligently to ring
Answer for the chemotherapy of colon cancer, the nano material of thermotherapy and its preparation method and application.
The purpose of the present invention can be achieved through the following technical solutions:
The present invention provides the chemotherapy for colon cancer, the nano material of thermotherapy of a kind of hydrogen sulfide intelligent response, is poly-
The copper base metal organic backbone nano material of the package colon cancer chemotherapy medicament of vinylpyrrolidone modification;The nano material can
Copper sulfide is generated in conjunction with the Endogenous Hydrogen Sulfide at colon tumor position, while releasing chemotherapeutics.
Preferably, the chemotherapeutics is drug for colon cancer chemotherapy, including curcumin, 5 FU 5 fluorouracil or
Adriamycin.It is further preferred that the chemotherapeutics is curcumin.
Preferably, the partial size for wrapping up the copper base metal organic framework material of chemotherapeutics is about 110nm.
The present invention also provides the chemotherapy for colon cancer, the systems of the nano material of thermotherapy of a kind of hydrogen sulfide intelligent response
Preparation Method, comprising the following steps:
(1) preparation of the copper base metal organic framework material of chemotherapeutics is wrapped up
Copper acetate and trimesic acid are dissolved into different solvents by (1-1) respectively, obtain copper acetate solution and equal benzene three
Formic acid solution,
(1-2) in the reactor be added curcumin and and part steps (1-1) in trimesic acid solution,
(1-3) under conditions of heating and stirring, copper acetate solution and remaining equal benzene three that step (1-1) is obtained
Formic acid solution is added dropwise in reactor from two sseparated channels of syringe pump respectively,
After (1-4) completion of dropwise addition, washing obtains the copper base metal organic framework material of package chemotherapeutics;
(2) preparation of the copper metal organic framework material of polyvinyl pyrrolidon modified packaging medicine
Polyvinylpyrrolidone is added to the copper base metal organic backbone for the package chemotherapeutics that step (1-4) obtains
It in material, stirs, is centrifuged at room temperature, washing obtains the copper metal organic backbone of polyvinyl pyrrolidon modified packaging medicine
Material, the as chemotherapy for colon cancer, the nano material of thermotherapy of the hydrogen sulfide intelligent response.
The available copper with water-soluble package chemotherapeutics very well is modified by polyvinylpyrrolidone (PVP)
Base Metal organic backbone nano material can be used for chemotherapy, the thermotherapy synergistic treatment of colon cancer.
Preferably, in step (1-1), the molar ratio of copper acetate and trimesic acid is 3:2.
Preferably, in step (1-1), copper acetate is dissolved in the mixed solvent of ethyl alcohol Yu dimethylformamide volume ratio 1:1
In;Trimesic acid is dissolved in dimethylformamide.
Preferably, the ratio between dosage of curcumin and trimesic acid is 1~5mg:21mg.
Preferably:
The trimesic acid solution being added in step (1-2) is the 50~100% of whole trimesic acid solution;Into one
Walk 50% that the trimesic acid solution being added in preferred steps (1-2) is whole trimesic acid solution;
In step (1-3), the temperature of heating is 45 DEG C;
In step (1-4), washing is multiple using ethanol washing;
In step (2), the time stirred at room temperature is 30min.
Preferably, the copper base metal organic backbone of the polyvinylpyrrolidone and package chemotherapeutics that are added in step (2)
The mass ratio of material is 0.25~2:1.
The present invention also provides chemotherapy, the nano materials of thermotherapy for colon cancer of a kind of hydrogen sulfide intelligent response to tie
Application in the optoacoustic diagnosis of intestinal cancer and photo-thermal-chemotherapy synergistic treatment medicine.
Preferably, which reacts with the Endogenous Hydrogen Sulfide at colon tumor position generates copper sulfide, and near-infrared is inhaled
Receipts are remarkably reinforced, while releasing chemotherapeutics curcumin, to trigger the function of photoacoustic imaging, photo-thermal therapy and chemotherapy.
The present invention has selected easy preparation and macroporosity, high surface area, the copper of adjustable shape and aperture and controlled surface
Base Metal organic backbone, using the above feature we by a kind of chemotherapy with high degree of biocompatibility and biodegradable
Drug (preferably native chemical therapeutic agent curcumin) is wrapped in copper base metal organic backbone.PVP wraps up metal organic framework energy
Enough improve the bio-compatibility of material.The copper base metal organic framework material of the package colon cancer drug curcumin of PVP modification,
Colon tumor position is reached by intravenous injection, is reacted with the Endogenous Hydrogen Sulfide at colon tumor position and generates copper sulfide, it is close red
Outer absorption is remarkably reinforced, while releasing chemotherapeutics curcumin, to trigger the function of photoacoustic imaging and photo-thermal therapy, chemotherapy
Energy.
The copper base metal organic framework material of the package colon cancer drug curcumin of PVP modification, which is dissolved in solution, carries out material
Expect that optoacoustic and light thermal property are studied:
The Endogenous Hydrogen Sulfide that colon tumor position is simulated with NaHS, by the Copper base material of the packaging medicine of PVP modification
Material is distributed in water, after the NaHS response of various concentration is added, is separated the curcumin of release by dialysing, benefit
The burst size of curcumin is surveyed with high performance liquid chromatography.
The copper base metal organic framework material of the packaging medicine of PVP modification is distributed in water, the sulphur of various concentration is added
After sodium hydride response, the near infrared absorption at the 980nm before and after NaHS is added is surveyed using ultraviolet-uisible spectrophotometer.
According to test result as can be seen that the absorption at 980nm is remarkably reinforced.In addition, various concentration is added using optoacoustic instrument test
The intensity of photoacoustic signal after NaHS.The results show that photoacoustic signal is remarkably reinforced after NaHS is added, and with sulphur
It hydrogenates na concn to increase, photoacoustic signal gradually increases.Meanwhile it being tested with light thermal imaging system and various concentration NaHS is added
Photo-thermal temperature rise effect, the results show that it is significantly raised that photo-thermal temperature rise effect after NaHS is added, also, with NaHS
Concentration increases, and photo-thermal temperature rise effect gradually increases.
The copper base metal organic framework material of the package colon cancer drug curcumin of PVP modification is examined in mouse tumor optoacoustic
The disconnected application on therapeutic agent.
Before experiment, HCT116 mouse tumor model is constructed first, and material is passed through in tail vein injection to Mice Body, benefit
With the photoacoustce signal intensity at optoacoustic instrument monitoring different time mouse tumor position.Material is entering in Mice Body as the result is shown
There is apparent photoacoustic signal in 2h, this illustrates that material is reacted with the highly expressed hydrogen sulfide in colon tumor position and generates copper sulfide,
Trigger the function of photoacoustic imaging.
As known from the above, PVP modification package colon cancer drug curcumin copper base metal organic framework material for pair
When mouse junction cancer carries out the drug of diagnosing and treating, directly by the reagent of parenteral solutions state, and by optoacoustic at
As instrument and 980nm laser carry out diagnoses and treatment.
Compared with prior art, the invention has the following advantages: the present invention has high table using colon tumor position
This feature of the Endogenous Hydrogen Sulfide reached has invented the copper-based of package chemotherapeutics (preferably native chemical therapeutic agent curcumin)
Metal organic framework nano material, the nano material pass through behind intravenous injection arrival colon tumor position and in tumor locus
Property hydrogen sulfide in source, which combines, generates copper sulfide, while discharging chemotherapeutics, the function of triggering photoacoustic imaging, photo-thermal therapy and chemotherapy.
Detailed description of the invention
Fig. 1 is the SEM spectrum of each stage product in embodiment 1, wherein Fig. 1 a is that the copper base metal of packaging medicine is organic
The SEM spectrum of skeleton, Fig. 1 b are the SEM spectrum of the copper base metal organic framework material of the packaging medicine of PVP modification.
Fig. 2 is the TEM map for the nano material being prepared in embodiment 1, and Fig. 2 a is the packaging medicine of PVP modification
The TEM map of copper base metal organic framework material, Fig. 2 b are the TEM map being added after sodium hydrosulfide response.
Fig. 3 is that the copper base metal organic framework material addition of the packaging medicine of the modification of PVP made from embodiment 1 is different dense
Near infrared absorption map after spending sodium hydrosulfide.3a is near infrared absorption curve spectrum, and 3b is at near-infrared 980nm
Absorption value.
Fig. 4 is that the copper base metal organic framework material addition of the packaging medicine of the modification of PVP made from embodiment 1 is different dense
Photoacoustic imaging map after the sodium hydrosulfide of degree.
Fig. 5 is that the copper base metal organic framework material addition of the packaging medicine of the modification of PVP made from embodiment 1 is different dense
Photo-thermal temperature rise effect map after the sodium hydrosulfide of degree.
Fig. 6 is the copper base metal organic framework material of the packaging medicine of the modification of PVP made from embodiment 1 in vivo tumor
The pcolor and photoacoustic signal value of middle photoacoustic imaging variation.
Specific embodiment
The present invention is described in detail with specific embodiment below in conjunction with the accompanying drawings.
Embodiment 1
A kind of chemotherapy for colon cancer, the nano material of thermotherapy of hydrogen sulfide intelligent response, are polyvinylpyrrolidine
The copper base metal organic backbone nano material of the package colon cancer chemotherapy medicament of ketone modification;The nano material can be with colon tumor
The Endogenous Hydrogen Sulfide at position, which combines, generates copper sulfide, while releasing chemotherapeutics.
Preparation method is as follows:
(1) firstly, the copper acetate for weighing 30mg is dissolved in 10mL dimethylformamide and the mixing of ethyl alcohol volume ratio 1:1 is molten
In liquid, weighs 21mg trimesic acid and be dissolved in 10mL dimethylformamide.Take the trimesic acid of the above-mentioned preparation of 5mL in anti-
It answers in device while the mixing of 3mg curcumin is added, under 45 DEG C of stirrings, by 10 mL copper acetate solutions and residue 5mL trimesic acid
Solution is added in reactor from two sseparated channels of syringe pump, uses ethanol washing 3 times after completion of dropwise addition, after washing
Material be distributed in ethyl alcohol to get to package chemotherapeutics copper base metal organic framework material.
(2) by the metal organic framework nano material 1:1 in mass ratio of polyvinylpyrrolidone (PVP) and packaging medicine
Mixing, stirs 30min at room temperature.Centrifuge washing obtains the copper base metal organic framework material of the packaging medicine of PVP modification.
Fig. 1 a and Fig. 1 b are respectively the packaging medicine of the metal organic framework nano material for wrapping up chemotherapeutics, PVP modification
Copper base metal organic framework material SEM, as can be seen from the figure coat PVP before and after the material structure there is no become
Change, partial size is almost unchanged, about 110nm.
Fig. 2 a and Fig. 2 b are respectively that NaHS is added in the copper base metal organic framework material of the packaging medicine of PVP modification
The TEM of front and back schemes, and as can be seen from the figure material partial size after NaHS is added by 110nm has been reduced to 15nm, shows to add
After entering NaHS, metal organic frame it is destructurized.
Embodiment 2
The copper base metal organic backbone for the package colon cancer drug curcumin for taking PVP made from a certain amount of embodiment 1 to modify
Material is scattered in deionized water, and is prepared and obtained the NaHS of various concentration, its near infrared absorption curve is detected.
Fig. 3 is the copper base metal organic framework material and various concentration sulphur of the package colon cancer drug curcumin of PVP modification
Near infrared absorption after sodium hydride response, the absorption of material 980 nm of near-infrared after NaHS is added is bright known in figure
Aobvious enhancing.Absorption value before addition NaHS at 980nm is about 0.02, after addition 4mM NaHS at 980nm
Absorption value is about 0.55, and absorption value increases 25 times, and with the increase near-infrared 980nm of NaHS concentration at
Absorption gradually increases.This is because the copper ion being added after NaHS in copper base metal organic backbone is given birth in conjunction with sulphion
At the copper sulfide with stronger near infrared absorption.
Embodiment 3
The copper base metal organic backbone for the package colon cancer drug curcumin for taking PVP made from a certain amount of embodiment 1 to modify
Material is scattered in deionized water, and is prepared and obtained the NaHS of various concentration, and the variation of its photoacoustic signal is detected.
Fig. 4 is that the copper base metal organic framework material of the package colon cancer drug curcumin of PVP modification is different dense in addition
Solution photoacoustic imaging effect picture after spending NaHS response, material photoacoustic imaging after NaHS is added known in figure
Effect is remarkably reinforced, and with the increase of NaHS concentration, the trend of enhancing is presented in optoacoustic effect.When NaHS increases
Photoacoustic signal increases 6 times when being added to 4mM.This is because the copper ion after NaHS in copper base metal organic backbone is added
Copper sulfide is generated in conjunction with sulphion to trigger the function of photoacoustic imaging.
Embodiment 4
The copper base metal organic backbone for the package colon cancer drug curcumin for taking PVP made from a certain amount of embodiment 1 to modify
Material is scattered in deionized water, and is prepared and obtained the NaHS of various concentration, its photo-thermal temperature rise effect is detected.Photo-thermal is real
Test is with 980nm laser irradiation 15min (1W/cm2).
Fig. 5 is the copper base metal organic framework material and various concentration sulphur of the package colon cancer drug curcumin of PVP modification
Sodium hydride response after solution photo-thermal temperature rise effect, You Tuzhong it is found that with NaHS concentration increase, photo-thermal temperature rise effect
It gradually increases.Material, which is added before sodium hydrosulfide, only increases 5 DEG C, is unable to reach when carrying out photo-thermal therapy for mouse
The temperature for melting tumour cell, and the solution being added after 4mM NaHS increases 21 DEG C, and NaHS phase is not added
Than increasing 4 times, it is sufficient to melt tumour cell.
Embodiment 5
HCT116 tumor model is constructed to mouse, diameter 5mm is grown in tumour, carries out optoacoustic test.We tie carrying
The tumor mouse of intestinal cancer is before the copper base metal organic framework material reagent of the package colon cancer drug curcumin of injection PVP modification
The photoacoustic signal of the tumor locus of 1h, 2h, 4h, 8h and imaging effect are monitored after (blank group), and injection.
From photoacoustic imaging signal graph (Fig. 6) as can be seen that the reagent by intravenous injection to after 1h in Mice Body in tumour
Faint signal is observed at position, and signal is most strong when 2h, and signal gradually weakens after 2h.It can be more from the pcolor of photoacoustic imaging
Intuitively find out the effect of photoacoustic imaging.And apparent signal is as can be seen from the figure not observed in surrounding tissue.
The reagent, which only passes through intravenous injection arrival colon tumor position, could be generated light after the triggering of colon tumor position richness hydrogen sulfide
Sound effective value.Because normal tissue concentration of hydrogen sulfide is very low, optoacoustic effect will not be triggered material has retention in normal organ
Fruit.By experimental result it can be seen that the diagnosis and treatment reagent has excellent optoacoustic diagnosis effect, and signal-to-noise ratio is high, when response
Between it is short the features such as.
Embodiment 6
The present embodiment is substantially the same manner as Example 1, the difference is that, in the present embodiment, chemotherapeutics is 5-Fu (5-
Fluorouracil).
Embodiment 7
The present embodiment is substantially the same manner as Example 1, the difference is that, in the present embodiment, chemotherapeutics is DOX (Ah mould
Element).
Embodiment 8
The present embodiment is substantially the same manner as Example 1, the difference is that, in the present embodiment, the use of step (1) curcumin
Amount is 1mg.
Embodiment 9
The present embodiment is substantially the same manner as Example 1, the difference is that, in the present embodiment, the use of step (1) curcumin
Amount is 5mg.
Embodiment 10
The present embodiment is substantially the same manner as Example 1, the difference is that, in the present embodiment, it is added all in step (1)
10mL trimesic acid solution mixes in reactor with curcumin, subsequent that copper acetate solution is individually added dropwise using syringe pump.
Embodiment 11
The present embodiment is substantially the same manner as Example 1, the difference is that, it is equal that 8mL is added in the present embodiment, in step (1)
Benzenetricarboxylic acid solution mixes in reactor with curcumin.
Embodiment 12
The present embodiment is substantially the same manner as Example 1, the difference is that, in the present embodiment, PVP and package chemotherapeutics
Copper base metal organic framework material mass ratio be 0.25:1.
Embodiment 13
The present embodiment is substantially the same manner as Example 1, the difference is that, in the present embodiment, PVP and package chemotherapeutics
Copper base metal organic framework material mass ratio be 2:1.
The above-mentioned description to embodiment is for ease of ordinary skill in the art to understand and use the invention.
Person skilled in the art obviously easily can make various modifications to these embodiments, and described herein one
As principle be applied in other embodiments without having to go through creative labor.Therefore, the present invention is not limited to the above embodiments,
Those skilled in the art's announcement according to the present invention, improvement and modification made without departing from the scope of the present invention all should be at these
Within the protection scope of invention.
Claims (10)
1. the chemotherapy for colon cancer, the nano material of thermotherapy of a kind of hydrogen sulfide intelligent response, which is characterized in that it is poly- second
The copper base metal organic backbone nano material of the package colon cancer chemotherapy medicament of alkene pyrrolidone modification;The nano material can be with knot
The Endogenous Hydrogen Sulfide at intestinal tumor position, which combines, generates copper sulfide, while releasing chemotherapeutics.
2. the chemotherapy for colon cancer, the nano material of thermotherapy of hydrogen sulfide intelligent response according to claim 1, special
Sign is that the chemotherapeutics is the drug for colon cancer chemotherapy, including curcumin, 5 FU 5 fluorouracil or adriamycin.
3. the preparation of the chemotherapy, the nano material of thermotherapy for colon cancer of hydrogen sulfide intelligent response as described in claim 1
Method, which comprises the following steps:
(1) preparation of the copper base metal organic framework material of chemotherapeutics is wrapped up
Copper acetate and trimesic acid are dissolved into different solvents by (1-1) respectively, obtain copper acetate solution and trimesic acid
Solution,
(1-2) in the reactor be added curcumin and and part steps (1-1) in trimesic acid solution,
(1-3) under conditions of heating and stirring, the copper acetate solution and remaining trimesic acid that step (1-1) is obtained are molten
Liquid is added dropwise in reactor from two sseparated channels of syringe pump respectively,
After (1-4) completion of dropwise addition, washing obtains the copper base metal organic framework material of package chemotherapeutics;
(2) preparation of the copper metal organic framework material of polyvinyl pyrrolidon modified packaging medicine
Polyvinylpyrrolidone is added to the copper base metal organic framework material for the package chemotherapeutics that step (1-4) obtains
In, it stirs, is centrifuged at room temperature, washing obtains the copper metal organic framework material of polyvinyl pyrrolidon modified packaging medicine,
The as chemotherapy for colon cancer, the nano material of thermotherapy of the hydrogen sulfide intelligent response.
4. the chemotherapy for colon cancer, the system of the nano material of thermotherapy of hydrogen sulfide intelligent response according to claim 3
Preparation Method, which is characterized in that in step (1-1), the molar ratio of copper acetate and trimesic acid is 3:2.
5. hydrogen sulfide intelligent response according to claim 3 or 4 for the chemotherapy of colon cancer, the nano material of thermotherapy
Preparation method, which is characterized in that in step (1-1), copper acetate is dissolved in the mixing of ethyl alcohol Yu dimethylformamide volume ratio 1:1
In solvent;Trimesic acid is dissolved in dimethylformamide.
6. the chemotherapy for colon cancer, the system of the nano material of thermotherapy of hydrogen sulfide intelligent response according to claim 3
Preparation Method, which is characterized in that the ratio between dosage of curcumin and trimesic acid is 1~5mg:21mg.
7. the chemotherapy for colon cancer, the system of the nano material of thermotherapy of hydrogen sulfide intelligent response according to claim 3
Preparation Method, it is characterised in that:
The trimesic acid solution being added in step (1-2) is the 50~100% of whole trimesic acid solution;
In step (1-3), the temperature of heating is 45 DEG C;
In step (1-4), washing is multiple using ethanol washing;
In step (2), the time stirred at room temperature is 30min.
8. the chemotherapy for colon cancer, the system of the nano material of thermotherapy of hydrogen sulfide intelligent response according to claim 3
Preparation Method, which is characterized in that the organic bone of copper base metal of the polyvinylpyrrolidone and package chemotherapeutics that are added in step (2)
The mass ratio of frame material is 0.25~2:1.
9. hydrogen sulfide intelligent response as described in claim 1 for the chemotherapy of colon cancer, the nano material of thermotherapy in colon
Application in the optoacoustic diagnosis of cancer and photo-thermal-chemotherapy combined therapeutic agent.
10. hydrogen sulfide intelligent response according to claim 9 is answered for the chemotherapy of colon cancer, the nano material of thermotherapy
With, which is characterized in that the nano material is reacted with the Endogenous Hydrogen Sulfide at colon tumor position generates copper sulfide, near infrared absorption
It is remarkably reinforced, while releasing chemotherapeutics curcumin, to trigger the function of photoacoustic imaging, photo-thermal therapy and chemotherapy.
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111234250A (en) * | 2020-02-18 | 2020-06-05 | 盐城工学院 | Bidirectional fluorescent hydrogen sulfide probe and application thereof |
CN114668853A (en) * | 2022-03-10 | 2022-06-28 | 东华大学 | Allicin-containing tumor in-situ response nanoparticle and preparation and application thereof |
CN115120719B (en) * | 2022-05-24 | 2023-10-03 | 浙江中医药大学 | Self-assembled nano-sheet for synergistic treatment of colon cancer and preparation method thereof |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102961753A (en) * | 2012-12-06 | 2013-03-13 | 东华大学 | Copper sulfide/mesoporous silicon dioxide core-shell nano material as well as preparation method and application thereof |
US20150018486A1 (en) * | 2007-09-21 | 2015-01-15 | Cytlmmune Sciences, Inc. | Nanotherapeutic Colloidal Metal Compositions and Methods |
CN105126113A (en) * | 2015-08-31 | 2015-12-09 | 郑州大学 | Preparation method and application of transferrin modified hollow mesoporous copper sulfide/artesunate nanoparticles |
CN108238628A (en) * | 2018-02-02 | 2018-07-03 | 上海师范大学 | The synthesis of cuprous oxide class material and its application on photoacoustic technique detection sulfide |
-
2019
- 2019-06-27 CN CN201910570568.XA patent/CN110448540B/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20150018486A1 (en) * | 2007-09-21 | 2015-01-15 | Cytlmmune Sciences, Inc. | Nanotherapeutic Colloidal Metal Compositions and Methods |
CN102961753A (en) * | 2012-12-06 | 2013-03-13 | 东华大学 | Copper sulfide/mesoporous silicon dioxide core-shell nano material as well as preparation method and application thereof |
CN105126113A (en) * | 2015-08-31 | 2015-12-09 | 郑州大学 | Preparation method and application of transferrin modified hollow mesoporous copper sulfide/artesunate nanoparticles |
CN108238628A (en) * | 2018-02-02 | 2018-07-03 | 上海师范大学 | The synthesis of cuprous oxide class material and its application on photoacoustic technique detection sulfide |
Non-Patent Citations (1)
Title |
---|
LU AN等: ""In situ sulfidation of Cu2O by endogenous H2S for colon cancer theranostics"", 《ANGEW.CHEM.INT. ED》 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111234250A (en) * | 2020-02-18 | 2020-06-05 | 盐城工学院 | Bidirectional fluorescent hydrogen sulfide probe and application thereof |
CN111234250B (en) * | 2020-02-18 | 2021-12-10 | 盐城工学院 | Bidirectional fluorescent hydrogen sulfide probe and application thereof |
CN114668853A (en) * | 2022-03-10 | 2022-06-28 | 东华大学 | Allicin-containing tumor in-situ response nanoparticle and preparation and application thereof |
CN114668853B (en) * | 2022-03-10 | 2023-08-04 | 东华大学 | Allicin-containing tumor in-situ response nanoparticle and preparation and application thereof |
CN115120719B (en) * | 2022-05-24 | 2023-10-03 | 浙江中医药大学 | Self-assembled nano-sheet for synergistic treatment of colon cancer and preparation method thereof |
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