CN116239153A - FeMoO 4 Acid response sound power material and preparation method and application thereof - Google Patents
FeMoO 4 Acid response sound power material and preparation method and application thereof Download PDFInfo
- Publication number
- CN116239153A CN116239153A CN202211612827.9A CN202211612827A CN116239153A CN 116239153 A CN116239153 A CN 116239153A CN 202211612827 A CN202211612827 A CN 202211612827A CN 116239153 A CN116239153 A CN 116239153A
- Authority
- CN
- China
- Prior art keywords
- mixed solution
- femoo
- acid
- preparation
- ferric
- 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
- 239000000463 material Substances 0.000 title claims abstract description 67
- 239000002253 acid Substances 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims description 25
- 230000004044 response Effects 0.000 title claims description 17
- 239000011259 mixed solution Substances 0.000 claims abstract description 44
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims abstract description 28
- MEFBJEMVZONFCJ-UHFFFAOYSA-N molybdate Chemical compound [O-][Mo]([O-])(=O)=O MEFBJEMVZONFCJ-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000001027 hydrothermal synthesis Methods 0.000 claims abstract description 14
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 12
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 12
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 238000002156 mixing Methods 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims abstract description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 25
- 239000012266 salt solution Substances 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 8
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 7
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 7
- 230000001225 therapeutic effect Effects 0.000 claims description 6
- 150000002505 iron Chemical class 0.000 claims description 4
- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 claims description 4
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical class [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 238000009472 formulation Methods 0.000 claims description 2
- RUTXIHLAWFEWGM-UHFFFAOYSA-H iron(3+) sulfate Chemical compound [Fe+3].[Fe+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O RUTXIHLAWFEWGM-UHFFFAOYSA-H 0.000 claims description 2
- 229910000360 iron(III) sulfate Inorganic materials 0.000 claims description 2
- 238000009210 therapy by ultrasound Methods 0.000 claims 1
- 230000002378 acidificating effect Effects 0.000 abstract description 18
- 230000009471 action Effects 0.000 abstract description 17
- 230000000694 effects Effects 0.000 abstract description 10
- 230000005909 tumor killing Effects 0.000 abstract 1
- 238000002604 ultrasonography Methods 0.000 description 18
- 230000007935 neutral effect Effects 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 12
- 239000002105 nanoparticle Substances 0.000 description 12
- 238000011282 treatment Methods 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 10
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 8
- 210000004881 tumor cell Anatomy 0.000 description 8
- 239000003642 reactive oxygen metabolite Substances 0.000 description 7
- ZKSVYBRJSMBDMV-UHFFFAOYSA-N 1,3-diphenyl-2-benzofuran Chemical compound C1=CC=CC=C1C1=C2C=CC=CC2=C(C=2C=CC=CC=2)O1 ZKSVYBRJSMBDMV-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 230000015556 catabolic process Effects 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 229910052742 iron Inorganic materials 0.000 description 5
- 230000002147 killing effect Effects 0.000 description 5
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 5
- 229960000907 methylthioninium chloride Drugs 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 239000012378 ammonium molybdate tetrahydrate Substances 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- FIXLYHHVMHXSCP-UHFFFAOYSA-H azane;dihydroxy(dioxo)molybdenum;trioxomolybdenum;tetrahydrate Chemical compound N.N.N.N.N.N.O.O.O.O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O[Mo](O)(=O)=O.O[Mo](O)(=O)=O.O[Mo](O)(=O)=O FIXLYHHVMHXSCP-UHFFFAOYSA-H 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 3
- 230000022534 cell killing Effects 0.000 description 3
- 238000001493 electron microscopy Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000001132 ultrasonic dispersion Methods 0.000 description 3
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011031 large-scale manufacturing process Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229910052750 molybdenum Inorganic materials 0.000 description 2
- 239000011733 molybdenum Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000004626 scanning electron microscopy Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229910001448 ferrous ion Inorganic materials 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- QQOCLJJWXLOEJE-UHFFFAOYSA-N iron(ii) molybdate Chemical compound [Fe+2].[O-][Mo]([O-])(=O)=O QQOCLJJWXLOEJE-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000004627 transmission electron microscopy Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
Images
Classifications
-
- 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
- A61K41/0028—Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
- A61K41/0033—Sonodynamic cancer therapy with sonochemically active agents or sonosensitizers, having their cytotoxic effects enhanced through application of ultrasounds
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/58—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01G—COMPOUNDS CONTAINING METALS NOT COVERED BY SUBCLASSES C01D OR C01F
- C01G49/00—Compounds of iron
- C01G49/0018—Mixed oxides or hydroxides
Abstract
The invention provides a FeMoO 4 A method of making an acid responsive acoustic power material comprising: dissolving molybdate, thiourea and ferric salt in water, fully mixing to obtain a mixed solution A, adding polyvinylpyrrolidone, stirring to obtain a mixed solution B, carrying out hydrothermal reaction on the mixed solution B at 200-220 ℃, and separating after the reaction to obtain the material. The material can specifically respond to weak acidic conditions, and the substructure material after collapse has strong sound power performance, thereby overcoming the technical problem that the sound sensitizer kills cells indiscriminately under the action of ultrasoundAnd has excellent tumor killing effect.
Description
Technical Field
The invention relates to the field of ultrasonic responsive materials, in particular to a FeMoO 4 An acid response acoustic power material, a preparation method thereof and application thereof in preparing an acoustic power therapeutic preparation for tumors.
Background
Despite the continued development of medical technology in the last decade, cancer remains a major cause of death worldwide. Tumor cells contain more Reactive Oxygen Species (ROS) than normal cells, and are more susceptible to redox equilibrium thresholds, and thus are more sensitive to environmental ROS concentrations. When tumor cells and normal cells are simultaneously exposed to the same strength of exogenous ROS stimulus, the ROS levels within tumor cells are more likely than normal cells to reach a threshold that triggers cell death. Based on this property of tumor cells, enhancing ROS production and reducing the antioxidant capacity of tumor cells to disrupt tumor redox balance is currently a more effective cancer treatment strategy.
The traditional cancer treatment mode has the defects of long period, large side effect and the like, and seriously influences the clinical treatment effect of tumors and the living standard of patients. Under the action of ultrasonic waves (US), liquid bubbles in tissues grow and collapse to induce an acoustic cavitation effect, and the collapse center can generate local high temperature and high pressure to cause thermal effects and mechanical damage of specific tissues. Under the action of ultrasound with a certain frequency, the sound sensitive agent specifically enriched in tumor tissues can be activated and greatly aggravate cavitation effect in the original solution, and a large amount of ROS and other activated oxidation substances can be rapidly generated in a short time.
Ultrasonic power therapy (SDT) combines ultrasonic waves with a sonosensitizer to achieve specific killing efficacy against tumor cells with low intensity and short time of ultrasonic action. At the same time, ultrasound power therapy (SDT) can accomplish site-directed ablation of tumor tissue due to the high tissue penetration depth and space-time controllability of high frequency Ultrasound (US). However, in practical operation, the sonosensitizer often has the problems of low efficiency, easy wide area influence on surrounding tissues, and the like.
At present, the killing effect of the acoustic power treatment is still limited, so that the development of the acoustic sensitizer activated by ultrasound in the tumor microenvironment is required, the action range of the acoustic sensitizer is controlled, the utilization efficiency of the acoustic sensitizer at the tumor tissue part is improved, and more efficient tumor treatment is realized.
The patent with the publication number of CN103754954B discloses a preparation method of a ferrous molybdate nanocube material, which belongs to the preparation of a morphology-regulated ferric molybdate nanomaterial, and comprises the steps of mixing an iron source and a molybdenum source according to a molar ratio of (1.5-3): 1 are placed in a closed pressure-resistant reaction vessel, the alcohol-water mixed solution is taken as a solvent, sodium acetate and polyvinylpyrrolidone which are 0.3-2.0 percent of the mass of the alcohol-water mixed solution are respectively added as auxiliary agents, and are stirred and mixed uniformly, and the reaction is carried out for 8-40 hours at the temperature of 100-250 ℃. The iron (II) molybdate nanocubes are prepared for the first time by adopting a one-step liquid phase method, the used raw materials are cheap and easy to obtain, the preparation steps are simple, the operation controllability is high, the obtained product is single crystals with uniform particle size distribution and proper particle size, and the large-scale industrial production is easy.
The invention provides a FeMoO 4 The acid response acoustic power material can specifically respond to weak acidic conditions, and the substructure material of the material after collapse has strong acoustic power performance, and has good application space in tumor treatment.
Disclosure of Invention
Aiming at the bottleneck problem existing in the prior art, the invention provides a FeMoO 4 An acid response sound power material, a preparation method and application thereof. FeMoO provided by the invention 4 The acoustic power material has the acoustic power performance in response to weak acid conditions in the tumor microenvironment, so as to solve the problems of weak specificity to tumor tissues, low treatment efficiency and the like of the acoustic power material.
The invention provides the following technical scheme:
FeMoO provided by the invention 4 The acid response acoustic power material can realize specific acoustic power treatment on tumor tissues under the action of low-intensity ultrasound under the assistance of weak acidic conditions of tumor microenvironment. In a weak acidic environment of tumor tissues, the material structure is easy to collapse, and compared with a neutral environment, the material shows strong sound dynamic performance under the action of low-intensity ultrasonic waves. The acid-responsive therapeutic material enhances the ultrasonic dynamic therapeutic effect by utilizing the weak acidic condition of the tumor microenvironment, and has important significance in tumor treatment.
To date, there is no acoustic power treatment material developed in the art that utilizes weak acid environment to sensitize acoustic power performance at tumor sites by active collapse, and the present invention fills this gap. The preparation method has the advantages of simple process, low cost, good dispersivity and stability in neutral environment, and the like, and is suitable for large-scale production.
FeMoO 4 The preparation method of the acid response acoustic power material comprises the following steps:
s1: dissolving molybdate, thiourea and ferric salt in water, and fully mixing to obtain a mixed solution A;
s2: adding polyvinylpyrrolidone into the mixed solution A obtained in the step S1, and stirring to obtain a mixed solution B;
s3: carrying out hydrothermal reaction on the mixed solution B obtained in the step S2, and separating after the reaction to obtain the FeMoO 4 The acid is responsive to the acoustic motive material.
According to the preparation method provided by the invention, thiourea is used as a reducing agent to reduce molybdate and ferric iron, and then the material is prepared through hydrothermal reaction, and in the preparation process, the iron source and molybdenum source consumption, the hydrothermal reaction temperature and time and other parameters are regulated and controlled, so that the ferrous molybdate nano particles which have loose structures and can stably exist in a neutral environment and have a nano cluster structure are finally prepared. In an acidic solution, the nano cluster structure collapses along with the improvement of the dissolution efficiency of ferrous ions, so that the material is dispersed into finer nano particles, the specific surface area of the material is improved, and the improvement of the sound power performance is facilitated.
Preferably, in the step S1, the trivalent iron salt is one of ferric chloride, ferric nitrate, and ferric sulfate.
Preferably, in the S1, the ratio of the amounts of molybdate, thiourea, ferric salt and water is 0.17mmol:5-7mmol:0.05-0.75mmol:20-80ml. Further preferably, the ratio of the amount of molybdate, thiourea, ferric salt and water is 0.17mmol:6mmol:0.2mmol:30ml, and stirred for 30min.
Preferably, in the step S1, molybdate and thiourea are dissolved in water and fully mixed to obtain a mixed solution a; and fully mixing the mixed solution a and ferric iron salt solution to obtain mixed solution A. The ferric salt solution prepared independently is mixed with the mixed solution a, so that the dosage of the iron source can be controlled more accurately.
Further preferably, the ferric salt solution is added dropwise to the mixed solution a; more preferably, the iron salt solution is dropwise added while the mixed solution a is stirred at 300-400 rpm.
Further preferably, the concentration of ferric salt in the ferric salt solution is 0.5-1g/ml; more preferably, the ferric salt solution is ferric chloride solution having a concentration of 1 g/ml.
Further preferably, the ferric salt solution is spent within 2 hours after configuration. More preferably, the ferric salt solution is stored in a refrigerator at 4 ℃ after being prepared to slow down the deterioration of the solution.
Further preferably, the ratio of the amount of the mixed solution a to the amount of the iron salt solution is 30 ml:20-120. Mu.l.
Preferably, in S2, the ratio of the amount of polyvinylpyrrolidone in the mixed solution B to the amount of the mixed solution a is 0.05 to 0.1g:30ml. Further preferably, the ratio of the amount of polyvinylpyrrolidone to the amount of the mixed solution a is 0.1g:30ml, and stirred at room temperature for 10min.
Preferably, in the step S2, the mixed solution B is sonicated at 40kHz for 5-30min. Further preferably, the mixed solution B is sonicated at 40khz,100w for 10min.
Preferably, in the step S3, the temperature of the hydrothermal reaction is 200-220 ℃, and the time of the hydrothermal reaction is 10-12h.
Preferably, in the step S3, the product obtained after the reaction is subjected to centrifugation, washing, ultrasonic dispersion, and further centrifugation to obtain the FeMoO dispersed therein 4 The acid responds to the supernatant of the sonodynamic material.
Further preferably, the centrifugation conditions are: the rotation speed of the centrifugal machine is 10000-14000rpm, and the time is 5-20min; more preferably, the centrifuge is rotated at 12000rpm for 15 minutes.
Further preferably, the parameter of ultrasonic dispersion is 20kHz,100-300W, the duty cycle is 25% -40%, and the time is 30min; more preferably, the ultrasonic dispersion parameter is 20kHz,250W, duty cycle is 33.3% and time is 30 minutes.
Further preferably, the conditions for the re-centrifugation are: the rotation speed of the centrifugal machine is 8000-12000rpm, and the time is 5-10min; more preferably, the centrifuge is rotated at 10000rpm for 8 minutes.
The invention also provides FeMoO prepared by the preparation method 4 The acid is responsive to the acoustic motive material. The FeMoO 4 The acid response acoustic power material is easy to collapse in weak acid environment, and has good dispersibility and stability under neutral condition.
Preferably, the FeMoO 4 The acid response pH of the acid response acoustic dynamic material is less than or equal to 6.5.
The invention also provides the FeMoO 4 Use of an acid responsive sonodynamic material in the preparation of a sonodynamic therapeutic formulation for tumors.
Compared with the prior art, the invention has at least the following advantages:
1. FeMoO provided by the invention 4 The acid response acoustic power material is a self-structure collapse material which is easy to collapse in weak acid environment. The invention develops an acoustic power treatment material for enhancing the acoustic power performance of a tumor part through active collapse by utilizing a weak acid environment for the first time.
2. FeMoO provided by the invention 4 The acid response sound power material can specifically respond to weak acidic conditions, and the substructure material of the material after collapse has strong sound power performance, so that on one hand, the technical problem that the sound sensitizer kills cells indiscriminately under the action of ultrasound is overcome, and on the other hand, the sound power material has very excellent effect of killing tumors.
3. The preparation method provided by the invention has the advantages of simple process, low cost, good dispersibility and stability of the prepared material in a neutral environment, and the like, and is suitable for large-scale production.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the application and together with the description, serve to explain the principles of the application.
FIG. 1 shows FeMoO in example 1 of the present invention 4 Electron microscopy of nanoparticles, wherein (a) (b) (c) is neutralNanoparticle electron microscopy under conditions (ph=7.4), (d) (e) (f) is nanoparticle electron microscopy under acidic conditions (ph=6.5), (a) (d) is low power scanning electron microscopy, (b) (e) is high power scanning electron microscopy, and (c) (f) is transmission electron microscopy.
FIG. 2 shows FeMoO in example 1 of the present invention 4 Energy spectra of Fe, mo, O elements of the nano particles under (a) neutral condition and (b) acidic condition.
FIG. 3 is a FeMoO of example 1 of the present invention 4 X-ray diffraction pattern of nanoparticles under neutral (ph=7.4) and acidic (ph=6.5) conditions.
FIG. 4 is a FeMoO of example 5 of the present invention 4 The degradation performance of the nano particles on DPBF under ultrasonic conditions is shown.
FIG. 5 is a FeMoO of example 5 of the present invention 4 Degradation performance profile of nanoparticles on MB under ultrasound conditions.
FIG. 6 shows FeMoO at different concentrations in example 6 of the present invention 4 Graph of cell killing capacity data of nanoparticles co-cultured with 4T1 cells for 24 hours under neutral conditions (ph=7.4) with or without ultrasound.
FIG. 7 shows FeMoO at different concentrations in example 6 of the present invention 4 Graph of cell killing capacity data of nanoparticles co-cultured with 4T1 cells for 24 hours under acidic conditions (ph=6.5) with or without ultrasound.
Detailed Description
Reference will now be made in detail to exemplary embodiments, examples of which are illustrated in the accompanying drawings. When the following description refers to the accompanying drawings, the same numbers in different drawings refer to the same or similar elements, unless otherwise indicated. The implementations described in the following exemplary examples are not representative of all implementations consistent with the present application. Rather, they are merely examples of apparatus and methods consistent with some aspects of the present application as detailed in the accompanying claims.
The terminology used in the present application is for the purpose of describing particular embodiments only and is not intended to be limiting of the present application. As used in this application and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It should also be understood that the term "and/or" as used herein refers to and encompasses any or all possible combinations of one or more of the associated listed items.
The invention will be further described with reference to the accompanying drawings and specific examples.
FeMoO provided by the invention 4 The preparation method of the acid response acoustic power material comprises the following steps:
s1: dissolving molybdate, thiourea and ferric salt in water, and fully mixing to obtain a mixed solution A;
s2: adding polyvinylpyrrolidone into the mixed solution A obtained in the step S1, and stirring to obtain a mixed solution B;
s3: carrying out hydrothermal reaction on the mixed solution B obtained in the step S2, and separating after the reaction to obtain the FeMoO 4 The acid is responsive to the acoustic motive material.
The present invention will be described in detail by way of examples. It is to be understood that the following examples are given solely for the purpose of illustration and are not to be construed as limitations upon the scope of the invention, since numerous insubstantial modifications and variations will be apparent to those skilled in the art in light of the above disclosure. The specific process parameters and the like described below are also merely examples of suitable ranges, i.e., one skilled in the art can make a suitable selection from the description herein and are not intended to be limited to the specific values described below.
Example 1:
this example provides a FeMoO 4 The preparation of an acid-responsive acoustic power material comprising:
0.210g of ammonium molybdate tetrahydrate and 0.456g of thiourea were dissolved in 30ml of pure water and stirred at 300rpm for 30 minutes at room temperature.
50. Mu.L of 1g/ml aqueous solution of ferric chloride was added dropwise to 30ml of the above solution, dispersed under 40kHz,100W of ultrasound for 10 minutes, and then 0.1g of polyvinylpyrrolidone was added thereto, followed by stirring at room temperature for 10 minutes to obtain a mixed solution.
The mixed solution is transferred into a hydrothermal reaction kettle, the reaction temperature is 200 ℃, and the reaction time is 10 hours. After the reaction solution is cooled to room temperature, centrifuging the obtained product at 12000r for 15min, washing with ethanol and water three times to remove redundant residues, dispersing for 30min under the ultrasonic action of 20kHz,250W and 33.3% duty ratio, centrifuging for 8min at 10000r again, and collecting supernatant to obtain ferrous molybdate solution. The supernatant was dried at 60℃and analyzed for solid samples.
In FIG. 1, (a) and (b) are respectively the FeMoO produced 4 SEM pictures of materials under different magnifications under neutral conditions, FIG. 1 (c) is FeMoO under neutral conditions 4 The neutral condition is ph=7.4. FIG. 1 (d) (e) is FeMoO under acidic conditions at different magnification 4 FIG. 1 (f) is an SEM image of FeMoO under acidic conditions 4 The acidic condition is ph=6.5.
As can be seen from a comparison of fig. 1, under acidic conditions, the material undergoes significant structural collapse, from nanoparticles around 200nm to smaller nanoparticles around 20 nm. From the energy spectrum analysis of FIG. 2, it is known that the material consists of Fe, mo and O elements. As can be seen from the X-ray diffraction pattern of FIG. 3, the phase composition of the material is not changed under neutral and acidic conditions, and the material can be determined to be FeMoO 4 。
Example 2:
FeMoO 4 The preparation of an acid-responsive acoustic power material comprising:
0.210g of ammonium molybdate tetrahydrate and 0.456g of thiourea were dissolved in 30ml of pure water and stirred at 300rpm for 30 minutes at room temperature.
100. Mu.L of 1g/ml aqueous solution of ferric chloride was added dropwise to 30ml of the above solution, dispersed under 40kHz,100W of ultrasound for 10 minutes, and then 0.1g of polyvinylpyrrolidone was added thereto, followed by stirring at room temperature for 10 minutes to obtain a mixed solution.
The mixed solution is transferred into a hydrothermal reaction kettle, the reaction temperature is 200 ℃, and the reaction time is 10 hours. After the reaction solution is cooled to room temperature, centrifuging the obtained product at 12000r for 15min, washing with ethanol and water three times to remove redundant residues, dispersing for 30min under the ultrasonic action of 20kHz,250W and 33.3% duty ratio, centrifuging for 8min at 10000r again, and collecting supernatant to obtain ferrous molybdate solution.
Example 3:
FeMoO 4 The preparation of an acid-responsive acoustic power material comprising:
0.105g of ammonium molybdate tetrahydrate and 0.228g of thiourea were dissolved in 30ml of pure water and stirred at 300rpm for 30 minutes at room temperature.
50. Mu.L of 1g/ml aqueous solution of ferric chloride was added dropwise to 30ml of the above solution, dispersed under 40kHz,100W of ultrasound for 10 minutes, and then 0.1g of polyvinylpyrrolidone was added thereto, followed by stirring at room temperature for 10 minutes to obtain a mixed solution.
The mixed solution is transferred into a hydrothermal reaction kettle, the reaction temperature is 200 ℃, and the reaction time is 10 hours. After the reaction solution is cooled to room temperature, centrifuging the obtained product at 12000r for 15min, washing with ethanol and water three times to remove redundant residues, dispersing for 30min under the ultrasonic action of 20kHz,250W and 33.3% duty ratio, centrifuging for 8min at 10000r again, and collecting supernatant to obtain ferrous molybdate solution.
Example 4:
FeMoO 4 The preparation of an acid-responsive acoustic power material comprising:
0.105g of ammonium molybdate tetrahydrate and 0.228g of thiourea were dissolved in 30ml of pure water and stirred at 300rpm for 30 minutes at room temperature.
50 mu L of 1g/ml of aqueous solution of ferric chloride is dropwise added to 30ml of the solution, dispersed for 10min under the ultrasonic action of 40kHz and 100W, added with 0.05g of polyvinylpyrrolidone and stirred for 10min at room temperature to obtain a mixed solution.
The mixed solution is transferred into a hydrothermal reaction kettle, the reaction temperature is 200 ℃, and the reaction time is 10 hours. After the reaction solution is cooled to room temperature, centrifuging the obtained product at 12000r for 15min, washing with ethanol and water three times to remove redundant residues, dispersing for 30min under the ultrasonic action of 20kHz,250W and 33.3% duty ratio, centrifuging for 8min at 10000r again, and collecting supernatant to obtain ferrous molybdate solution.
Example 5:
test of the sonodynamic therapeutic properties of the material prepared in example 1: the degradation properties of the material under ultrasonic conditions were monitored for p-diphenyl isobenzofuran (DPBF) and Methylene Blue (MB).
The material was washed by centrifugation after being immersed in neutral (ph=7.4) and acidic (ph=5.8) for 3 hours to obtain the material before and after the acid reaction. 100. Mu.L of DPBF (2 mM) and the material before and after the acid reaction were added to 3mL of ethanol/PBS buffer, 100. Mu.L of MB (1 mM) and the material before and after the acid reaction were added to 3mL of PBS buffer, and the absorption curves of the solutions were measured by an ultraviolet-visible spectrophotometer under the action of ultrasound at intervals of 2 minutes, respectively.
As can be seen from FIG. 4, under neutral conditions FeMoO 4 The DPBF degradation capability under the ultrasonic action of neutral condition is weaker than that of pure ultrasonic, namely the DPBF degradation capability does not show the sound power performance, and FeMoO after soaking in acidic condition 4 The ability to degrade DPBF is significantly improved. Meanwhile, as can be seen from FIG. 5, feMoO after the acid reaction 4 The performance of degrading MB under the action of ultrasound is also improved. Namely the FeMoO 4 The sound power material can effectively improve sound power performance in an acid environment.
Example 6:
the application of the material provided by the invention in the aspect of tumor cell killing is illustrated by the killing effect on the cell level. The material used was the material prepared in example 1. The cells selected were 4T1 mouse breast cancer cells, and the data obtained are shown in FIGS. 6 and 7.
As can be seen from fig. 6, under neutral conditions (ph=7.4), the effect of ferrous molybdate on tumor cell activity was controllable with increasing concentration, and there was no significant difference in ultrasound cell activity. As can be seen from FIG. 7, when the cell culture environment is adjusted to be acidic (pH=6.5), the ferrous molybdate can obviously kill cells under the action of ultrasound, and the killing effect on the cells can reach more than 85% when the material concentration is 60 mug/mL. The ferrous molybdate material has very good tumor treatment performance.
Other embodiments of the present application will be apparent to those skilled in the art from consideration of the specification and practice of the disclosure herein. This application is intended to cover any variations, uses, or adaptations of the application following, in general, the principles of the application and including such departures from the present disclosure as come within known or customary practice within the art to which the application pertains. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the application being indicated by the following claims.
It is to be understood that the present application is not limited to the precise arrangements and instrumentalities shown in the drawings, which have been described above, and that various modifications and changes may be effected without departing from the scope thereof. The scope of the application is limited only by the appended claims.
Claims (10)
1. FeMoO 4 The preparation method of the acid response acoustic power material is characterized by comprising the following steps of:
s1: dissolving molybdate, thiourea and ferric salt in water, and fully mixing to obtain a mixed solution A;
s2: adding polyvinylpyrrolidone into the mixed solution A obtained in the step S1, and stirring to obtain a mixed solution B;
s3: carrying out hydrothermal reaction on the mixed solution B obtained in the step S2, and separating after the reaction to obtain the FeMoO 4 The acid is responsive to the acoustic motive material.
2. The production method according to claim 1, wherein in S1, the trivalent iron salt is one of ferric chloride, ferric nitrate, and ferric sulfate.
3. The method according to claim 1, wherein in S1, the ratio of the amounts of molybdate, thiourea, ferric salt and water is 0.17mmol:5-7mmol:0.05-0.75mmol:20-80ml.
4. The preparation method according to claim 1, wherein in S1, molybdate and thiourea are dissolved in water and thoroughly mixed to obtain a mixed solution a; and fully mixing the mixed solution a and ferric iron salt solution to obtain mixed solution A.
5. The method according to claim 4, wherein,
the concentration of the ferric salt in the ferric salt solution is 0.5-1g/ml;
the ratio of the dosage of the mixed solution a to the dosage of the ferric salt solution is 30ml to 20-120 mu l.
6. The preparation method according to claim 1, wherein in S2, the ratio of the amount of polyvinylpyrrolidone in the mixed solution B to the amount of the mixed solution a is 0.05 to 0.1g:30ml.
7. The method according to claim 1, wherein,
in the step S2, the mixed solution B is subjected to ultrasonic treatment at 40kHz for 5-30min;
in the step S3, the temperature of the hydrothermal reaction is 200-220 ℃, and the time of the hydrothermal reaction is 10-12h.
8. FeMoO prepared by the preparation method according to any one of claims 1 to 7 4 The acid is responsive to the acoustic motive material.
9. The FeMoO of claim 8 4 An acid-responsive acoustic power material characterized in that the FeMoO 4 The acid response pH of the acid response acoustic dynamic material is less than or equal to 6.5.
10. The FeMoO of claim 8 4 Use of an acid responsive sonodynamic material in the preparation of a sonodynamic therapeutic formulation for tumors.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211612827.9A CN116239153A (en) | 2022-12-15 | 2022-12-15 | FeMoO 4 Acid response sound power material and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211612827.9A CN116239153A (en) | 2022-12-15 | 2022-12-15 | FeMoO 4 Acid response sound power material and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116239153A true CN116239153A (en) | 2023-06-09 |
Family
ID=86628518
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211612827.9A Pending CN116239153A (en) | 2022-12-15 | 2022-12-15 | FeMoO 4 Acid response sound power material and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116239153A (en) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012143739A1 (en) * | 2011-04-21 | 2012-10-26 | University Of Ulster | Sonodynamic therapy |
| CN103754954A (en) * | 2014-02-14 | 2014-04-30 | 中国矿业大学 | Preparation method of iron molybdenum oxide (II) nanocube |
| CN107213904A (en) * | 2017-05-08 | 2017-09-29 | 武汉工程大学 | A kind of preparation method of high activity, the monoclinic form iron molybdate nanosheets of crystal face exposure |
| CN107459064A (en) * | 2016-06-03 | 2017-12-12 | 中国科学院大连化学物理研究所 | A kind of nanocube accumulates layered mesoporous FeMoO4The preparation method of solid material |
| CN109574082A (en) * | 2018-11-28 | 2019-04-05 | 武汉科技大学 | A kind of original position core-shell structure molybdic acid iron powder body and preparation method thereof |
| CN110589894A (en) * | 2019-09-17 | 2019-12-20 | 北京化工大学 | Preparation method of hollow metal oxide nano material |
| US20200069727A1 (en) * | 2017-05-04 | 2020-03-05 | University Of Ulster | Calcium peroxides nanoparticles as adjuvant therapy |
| CN113816432A (en) * | 2021-09-06 | 2021-12-21 | 广东工业大学 | Nanosheet self-assembled spherical ferrous molybdate material and preparation method and application thereof |
-
2022
- 2022-12-15 CN CN202211612827.9A patent/CN116239153A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012143739A1 (en) * | 2011-04-21 | 2012-10-26 | University Of Ulster | Sonodynamic therapy |
| CN103754954A (en) * | 2014-02-14 | 2014-04-30 | 中国矿业大学 | Preparation method of iron molybdenum oxide (II) nanocube |
| CN107459064A (en) * | 2016-06-03 | 2017-12-12 | 中国科学院大连化学物理研究所 | A kind of nanocube accumulates layered mesoporous FeMoO4The preparation method of solid material |
| US20200069727A1 (en) * | 2017-05-04 | 2020-03-05 | University Of Ulster | Calcium peroxides nanoparticles as adjuvant therapy |
| CN107213904A (en) * | 2017-05-08 | 2017-09-29 | 武汉工程大学 | A kind of preparation method of high activity, the monoclinic form iron molybdate nanosheets of crystal face exposure |
| CN109574082A (en) * | 2018-11-28 | 2019-04-05 | 武汉科技大学 | A kind of original position core-shell structure molybdic acid iron powder body and preparation method thereof |
| CN110589894A (en) * | 2019-09-17 | 2019-12-20 | 北京化工大学 | Preparation method of hollow metal oxide nano material |
| CN113816432A (en) * | 2021-09-06 | 2021-12-21 | 广东工业大学 | Nanosheet self-assembled spherical ferrous molybdate material and preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| HEBA M. EL SHARKAWY ET AL.: "FeMoO4 nanoparticles as functional negative electrode material for high performance supercapacitor devices over a wide pH range", 《JOURNAL OF ENERGY STORAGE》, vol. 54, 13 July 2022 (2022-07-13), pages 1 - 9 * |
| 姚淑华;陈雪静;王海博;: "棒状FeMoO_4材料的制备及其活化性能", 精细化工, no. 05, 31 May 2020 (2020-05-31), pages 1033 - 1038 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Parial et al. | Gold nanorod production by cyanobacteria—a green chemistry approach | |
| CN107184978B (en) | Copper sulfide @ mesoporous silica nanocomposite and preparation method and application thereof | |
| CN105565506A (en) | Biological composite material loaded with magnetic nano particles with core-shell structure and preparation method and application of biological composite material | |
| CN108578716B (en) | Polydopamine-coated magnetic mesoporous silica nano material and preparation and application thereof | |
| CN112807430A (en) | Application of nano enzyme-based material | |
| CN113332427B (en) | Fe 2 O 3 @ Pt multifunctional nano-particle and preparation method and application thereof | |
| CN110882389B (en) | Titanium monoxide nano material and preparation method and application thereof | |
| CN113952984B (en) | High-catalytic-activity molybdenum-based nanoenzyme and preparation method and application thereof | |
| CN110327463B (en) | Nano material containing gadolinium polytungstate and preparation method thereof | |
| CN108785276A (en) | A kind of purposes of radio therapy sensitization nano material | |
| CN116239153A (en) | FeMoO 4 Acid response sound power material and preparation method and application thereof | |
| CN112121797A (en) | Magnetic TiO2Preparation method of graphene oxide composite material | |
| CN114159466B (en) | Hydroxyapatite/saccharomycete biological hybrid material and preparation method and application thereof | |
| CN113387395B (en) | Efficient magnetic response catalytic medical nano-particle and preparation method and application thereof | |
| Wang et al. | Effect of tourmaline addition on the structure of silica hollow microspheres prepared by a novel template method | |
| CN107233572B (en) | Preparation method and application of photothermal agent based on amyloid polypeptide as template | |
| CN114159588B (en) | Ternary alloy PtW-Mn-based nano probe, preparation method and application thereof | |
| CN112843231B (en) | Cell membrane coated Fe 3 O 4 @MnO 2 Targeting nano material and preparation method and application thereof | |
| CN104925870A (en) | Solvothermal method for preparing nano-grade ferroferric oxide | |
| CN106800315A (en) | A kind of ionic liquid assisted microwave synthesis radiation method synthesizes the method for extra small magnetic Nano cluster | |
| CN111406948A (en) | Preparation method and application of Grateloupia filicina polysaccharide-nano selenium | |
| CN106860864B (en) | Photosensitizer-loaded mesoporous organosilicon-gold nanoparticle triangular plate composite material and preparation method and application thereof | |
| CN115608350B (en) | Preparation method and application of heterojunction based on rod-shaped zinc oxide | |
| CN114948995B (en) | Ferro-manganese bimetal monatomic nano material and preparation method thereof | |
| CN115415512B (en) | Preparation method and application of platinum-zinc oxide heterojunction nano-particles |
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 |