CN110124034B - Nano metal organic framework cavitation material, synthetic method and application - Google Patents
Nano metal organic framework cavitation material, synthetic method and application Download PDFInfo
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- CN110124034B CN110124034B CN201910456223.1A CN201910456223A CN110124034B CN 110124034 B CN110124034 B CN 110124034B CN 201910456223 A CN201910456223 A CN 201910456223A CN 110124034 B CN110124034 B CN 110124034B
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- A—HUMAN NECESSITIES
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- 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
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- 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
- A61K49/223—Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
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- 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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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
- C08G83/008—Supramolecular polymers
Abstract
The invention discloses a nano metal organic framework cavitation material, a synthetic method and application, and belongs to the field of ultrasonic cavitation materials. The material takes a nano metal organic framework as a carrier and takes a cavitating agent active component as a carried substance, and the preparation method of the material comprises the following steps: 1) respectively dissolving a metal source and an organic ligand in a solvent to respectively obtain a metal source mother solution and an organic ligand mother solution; 2) mixing the metal source mother liquor and the organic ligand mother liquor obtained in the step 1) according to a ratio, heating for reaction, performing centrifugal separation, and drying to obtain a dried product; 3) dispersing the obtained dry product and the active component of the cavitating agent in a solvent, stirring, centrifugally separating and drying. Compared with lipid bubbles adopted in the prior art, the nano metal organic framework cavitation material can obviously improve the stability, prolong the circulation time in vivo, simultaneously improve the enrichment rate of the material at tumor parts and improve the curative effect of tumor treatment.
Description
Technical Field
The invention belongs to the field of ultrasonic cavitation materials, and particularly relates to a nano metal organic framework cavitation material, a synthetic method and application.
Background
Currently, the nanocarrier technology has been widely used in the biomedical field, and due to the rapid growth of tumors and abnormal vasculature, nanocarriers can be accumulated at tumor sites via the permeation and retention (EPR) effect. The main bottleneck is to increase the enrichment rate at the tumor site, and accumulation analysis of the tumor shows that only a small fraction of injected nanocarriers can reach the tumor tissue (about 0.7%). Furthermore, this parameter has not improved significantly over the last decades. Tumors from different patients or different regions of the same patient can also cause uneven distribution of nanocarriers within the tumor due to tumor heterogeneity. In addition, the higher interstitial pressure within solid tumors also limits the penetration of nanoparticles into tissues. Ultrasound is an important tool in the biomedical field, and can be used for inducing drug release from carriers, sonodynamic treatment of tumors, reversible opening of blood brain barriers and the like. And the ultrasound can focus on the region of interest in the deep part of the body, reducing the influence on the surrounding non-target region. Its biological effects can be divided into thermal and mechanical effects, among which cavitation is considered to be one of the most useful ultrasound-related phenomena in biomedicine. Ultrasonic cavitation refers to a series of dynamic processes of oscillation, expansion, contraction, implosion and the like of micro bubbles in liquid under ultrasonic irradiation, and the extreme physical phenomena of luminescence, high temperature, high pressure, discharge, micro jet and the like caused by the rapid release of energy in the micro bubbles at the moment of the explosion of the micro bubbles can be divided into stable cavitation and transient cavitation. The stable cavitation refers to the formation of tiny pores on the vascular endothelial cell membrane through the effects of shock waves, high-speed jet flow and the like, which is called as the "sound pore effect", and can increase the permeability of cells and tissues and the opening of a blood brain barrier and promote the concentration of drugs in a target area. Transient cavitation refers to the rapid expansion, contraction and even collapse of microbubbles under a high sound field to cause irreversible cell necrosis.
However, most of the conventional cavitating agents contain gas, and the lipid structure is used as an outer membrane outside the cavitating agent, which has instability, is difficult to realize long-time circulation in blood and has low enrichment rate at tumor sites, so that the cavitation treatment cannot achieve an ideal treatment state in the actual treatment process. Therefore, the key point for solving the problem is to find a carrier material which can be loaded with high efficiency and can realize directional release under the guidance of ultrasound.
The metal-organic framework structure is a material developed in 1990 from a metal to an organic substance through weak coordinate bonds, and is also called "metal sponge". It has a variety of structures that provide different morphologies, compositions, sizes, and chemical properties to the metal-organic framework structure, while also imparting its versatility and stimulus-responsive controlled drug release. While these modifications are made, the organometallic framework structure can still maintain controlled size, shape and high uniformity. In addition, the large specific surface area and high porosity of the material also promote the loading capacity of the material. In addition, it is a weak coordinate bond that forms a metal-organic framework structure, and biodegradability is also exhibited. In short, these properties make metal-organic framework structures possible for drug delivery, tumor therapy and therapy of other diseases, and the use of metal framework materials for loading of cavitating agents is not reported in the literature.
Disclosure of Invention
1. Problems to be solved
Aiming at the problems that the active ingredients of the existing cavitating agent have poor solubility, long-time circulation in blood is difficult to realize, and the enrichment ratio at a tumor part is low, so that ideal treatment effect of cavitation treatment is difficult to achieve, the invention provides a preparation method of a nano metal organic framework cavitation material and a material.
Furthermore, the invention provides application of the nano metal organic framework cavitation material, and the compound can be used for visual cavitation treatment of various cancers, especially cancers with thinner new blood vessels.
2. Technical scheme
In order to solve the problems, the technical scheme adopted by the invention is as follows:
the invention provides a nano metal organic framework cavitation material, which takes a nano metal organic framework as a carrier and a cavitating agent active component as a carried object, wherein the cavitating agent active component is selected from at least one of 1,1,1,3, 3-pentafluorobutane, perfluorobutane, perfluorohexane, perfluorohexyliodoalkane and tris (pentafluorophenyl) borane.
As a further improvement of the invention, the synthesis method of the material comprises the following steps:
1) respectively dissolving a metal source and an organic ligand in a solvent to respectively obtain a metal source mother solution and an organic ligand mother solution;
2) mixing the metal source mother liquor and the organic ligand mother liquor obtained in the step 1) according to a ratio, heating for reaction, performing centrifugal separation, and drying to obtain a dried product;
3) dispersing the dried product obtained in the step 2) and the active component of the cavitating agent in a solvent, stirring, centrifuging, and drying.
As a further improvement of the invention, the organic ligand is selected from one of terephthalic acid, 2-amino terephthalic acid, tetra (4-carboxyphenyl) porphine, 2-nitro terephthalic acid, 2-hydroxy terephthalic acid and trimesic acid, and the metal source is selected from one of tetravalent hafnium ion, tetravalent zirconium ion, trivalent iron ion, divalent copper ion and divalent zinc ion.
As a further improvement of the invention, the particle size of the nano metal organic framework cavitation material is 50-400 nm, and the loading amount of the active component of the cavitating agent is 5-60%.
As a further improvement of the invention, the molar concentration of the metal source mother liquor in the step 1) is 5-20 mmol/L, and the molar concentration of the organic ligand mother liquor is 20-45 mmol/L.
As a further improvement of the present invention, the solvent of step 1) and step 3) is selected from: one or more of methanol, ethanol, ethylene glycol, N-dimethylformamide, dichloromethane, trichloromethane, dimethyl sulfoxide and o-dichlorobenzene.
As a further improvement of the present invention, the molar concentration ratio of the metal source mother liquor to the organic ligand mother liquor in the step 2) is 1: (2-4); the heating reaction temperature is 50-90 ℃, and the reaction time is 12-30 hours.
As a further improvement of the present invention, in the step 3), the ratio of the mass of the cavitating agent active component added to the mass of the dried product is 1: (2-5).
As a further improvement of the invention, the nano metal organic framework cavitation material is applied to cancer cavitation treatment.
As a further improvement of the invention, the cavitation material is firstly enriched at the tumor part through an EPR effect, and undergoes liquid-gas phase change after ultrasonic targeted irradiation to become micron-sized bubbles to play a role, and the material has better ultrasonic cavitation and ultrasonic imaging effects.
As a further improvement of the invention, the cancers include breast, pancreatic, renal and liver cancers with thin neovasculature.
3. Advantageous effects
Compared with the prior art, the invention has the beneficial effects that:
(1) compared with lipid bubbles adopted in the prior art, the nano metal organic framework cavitation material provided by the invention has the advantages that the stability of the material can be obviously improved, the circulation time in vivo can be prolonged, the water solubility of the carried substance in the material can be obviously improved, the circulation time in vivo can be further prolonged, the used metal organic framework compound has higher carrying capacity, and the using amount of a medicament can be reduced.
(2) The nano metal organic framework cavitation material of the invention takes a metal organic framework compound as a carrier, and simultaneously, the inside of the metal organic framework compound is wrapped with a cavitation nucleus, on one hand, the sound pressure required by the induced cavitation effect is reduced by utilizing the cavitation nucleus, the permeability of tumor tissues is increased, and the curative effect of tumor treatment is improved, on the other hand, the nano material can reach the tumor part through the vascular endothelial gap and is easier to be enriched at the tumor part, and on the other hand, the micron material can not reach the tumor part through the vascular endothelial gap.
(3) The nano metal organic framework cavitation material firstly circulates in vivo in a nano form by utilizing the characteristic that the imaging effect of micron-sized bubbles is superior to that of the nano-sized bubbles during ultrasonic cavitation and ultrasonic imaging, and the cavitation material is changed into the micron-sized bubbles to play a role under the ultrasonic action after the circulation reaches the interior of a tumor, so that the material can have better ultrasonic cavitation and ultrasonic imaging effects after liquid-gas conversion.
(4) The preparation method of the nano metal organic framework cavitation material of the invention wraps the carried object in the shell in a liquid form, fully utilizes the characteristics of more stability, difficult overflow and high water solubility of the liquid in the material, ensures that the material circulates better in vivo, effectively prolongs the circulation time of the material in vivo, carries out liquid-gas phase change under the ultrasonic action after reaching a tumor part, converts the liquid-gas phase change into micron-sized gas to play the therapeutic action of a cavitating agent, has mild conditions, has low requirements on equipment, operation, environment and the like, and is beneficial to popularization.
Drawings
FIG. 1 is a diagram illustrating a state in which a nano metal organic framework material prepared in example 2 is dissolved in an aqueous solution;
FIG. 2 is an ultrasonic image of the nano metal organic framework cavitation material prepared in example 2;
FIG. 3 is a liquid-gas phase diagram of the nano metal organic framework cavitation material prepared in example 2; in the figure, a is an optical microscope picture before liquid-gas phase change; b is an optical microscope picture after liquid-gas phase change;
FIG. 4 is a comparison of fluorescence imaging of small animals of the nanometal organic frameworks and PCN-Fe (III) organometallic framework materials prepared in example 2; in the figure, a is a fluorescence imaging diagram of the nano metal organic framework prepared in example 2; b is a single PCN-Fe (III) organic metal framework fluorescence imaging picture.
Detailed Description
The invention is further described with reference to specific examples.
Example 1
The preparation method of the nano metal organic framework cavitation material comprises the following steps:
1) methanol is taken as a solvent, and a zirconium chloride solution with the molar concentration of 20mmol/L is prepared to be taken as a metal source mother solution; in addition, methanol is taken as a solvent, and a terephthalic acid methanol solution with the molar concentration of 40mmol/L is prepared to be taken as an organic ligand mother liquor;
2) respectively taking 10mL of metal source mother liquor and 10mL of organic ligand mother liquor, uniformly mixing, and placing in a 50mL reaction kettle, wherein the molar ratio of the metal source to the organic ligand in the mixed liquor is 1: 2; placing the reaction kettle in a 50 ℃ oven for reaction for 24 hours, taking out, centrifugally separating, and drying to obtain a dried product;
3) according to the mass ratio of 1: 3 sequentially weighing perfluorohexane and a dried product into a drying conical flask, adding dichloromethane with the same volume (the volume ratio of the added dichloromethane to the perfluorohexane is 1: 1), stirring for 24 hours after ultrasonic uniform dispersion, and centrifugally separating and drying to obtain the product.
Example 2
The preparation method of the nano metal organic framework cavitation material comprises the following steps:
1) taking an N, N-dimethylformamide solution as a solvent, and preparing a ferric trichloride solution with the molar concentration of 10mmol/L as a metal source mother solution; similarly, N-dimethylformamide solution is used as a solvent, and p-tetrakis (4-carboxyphenyl) porphine with the molar concentration of 30mmol/L is prepared to be used as organic ligand mother liquor;
2) respectively taking 10mL of metal source mother liquor and 10mL of organic ligand mother liquor, uniformly mixing, and placing in a 50mL reaction kettle, wherein the molar concentration ratio of the metal source mother liquor to the organic ligand mother liquor in the mixed liquor is 1: 3; placing the reaction kettle in a 90 ℃ oven for reaction for 24 hours, taking out, centrifugally separating, and drying to obtain a dried product;
3) according to the mass ratio of 1: 2, sequentially weighing 1,1,1,3, 3-pentafluorobutane and a dried product into a drying conical flask, adding dichloromethane with the same volume (the volume ratio of the added volume of the 1,1,1,3, 3-pentafluorobutane to the dichloromethane is 1: 1), stirring for 36 hours after ultrasonic uniform dispersion, and obtaining the product after centrifugal separation and drying.
Fig. 1 is a diagram illustrating a state that the nano metal organic framework material prepared in this embodiment is dissolved in an aqueous solution, and it can be seen from fig. 1 that the material prepared in the present invention has high solubility, uniformity and good dispersibility in water.
The nano metal organic frame material prepared in this example was placed in an ultrasonic imaging instrument, which was a Philips IU Elite color doppler ultrasonic diagnostic apparatus, using an L12-5 high-frequency linear array probe, setting a frequency of 5-12MHz and a mechanical index of 0.07, an agar dish was prepared in advance, PBS and the nano metal organic frame material were injected into the agar dish, and observed in B-mode and ultrasonic imaging (CEUS) modes with the ultrasonic imaging instrument, respectively, with the results shown in fig. 2.
The results show that the material prepared by the invention can enhance the ultrasonic imaging performance in B-mode and ultrasonic Contrast (CEUS) modes, and further show that the material can be used for ultrasonic imaging.
Placing the prepared nano metal organic framework cavitation material under an ultrasonic cavitation instrument for irradiation, wherein a is a liquid-gas phase change diagram of the material, and a is an optical microscope diagram before liquid-gas phase change; b is an optical microscope picture after liquid-gas phase change; as can be seen from fig. 3, the material undergoes liquid-gas phase transition under the irradiation of the ultrasonic cavitation apparatus to generate micron-sized bubbles, so that the micron-sized bubbles can be utilized to exert a better therapeutic effect of the cavitating agent on the tumor site, and thus it can be shown that the nano metal organic framework cavitation material of the present invention can be used for cancer cavitation therapy, particularly for breast cancer, pancreatic cancer, renal cancer, and liver cancer with thin neovasculature.
Example 3
The preparation method of the nano metal organic framework cavitation material comprises the following steps:
1) preparing a zirconium chloride solution with the molar concentration of 10mmol/L as a metal source mother solution by taking ethanol as a solvent, and preparing a trimesic acid ethanol solution with the molar concentration of 20mmol/L as an organic ligand mother solution by taking ethanol as a solvent;
2) respectively taking 20mL of metal source mother liquor and 20mL of organic ligand mother liquor, uniformly mixing, and placing in a 100mL reaction kettle, wherein the molar concentration ratio of the metal source mother liquor to the organic ligand mother liquor in the mixed liquor is 1: 2; placing the reaction kettle in an oven at 70 ℃ for reaction for 12 hours, taking out, centrifugally separating, and drying to obtain a dried product;
3) according to the mass ratio of 1: and 4, sequentially weighing perfluorobutane and a dried product into a drying conical flask, adding dichloromethane with the same volume (the volume ratio of the added dichloromethane to the perfluorohexane is 1: 1), stirring for 12 hours after ultrasonic uniform dispersion, and centrifugally separating and drying to obtain the product.
The material is observed by using an ultrasonic diagnostic apparatus, and the material is proved to be used for ultrasonic imaging.
Example 4
The preparation method of the nano metal organic framework cavitation material comprises the following steps:
1) preparing a zirconium chloride solution with the molar concentration of 15mmol/L as a metal source mother solution by taking methanol as a solvent, and preparing a tetra (4-carboxyphenyl) porphin methanol solution with the molar concentration of 45mmol/L as an organic ligand mother solution by taking methanol as a solvent;
2) respectively taking 15mL of metal source mother liquor and 15mL of organic ligand mother liquor, uniformly mixing, and placing in a 50mL reaction kettle, wherein the molar concentration ratio of the metal source mother liquor to the organic ligand mother liquor in the mixed liquor is 1: 3; placing the reaction kettle in a 60 ℃ oven for reaction for 30 hours, taking out, centrifugally separating, and drying to obtain a dried product;
3) according to the mass ratio of 1: 4, sequentially weighing perfluorohexyliodoalkane and a dried product into a drying conical flask, adding trichloromethane with the same volume (the volume ratio of the added trichloromethane to the perfluorohexyliodoalkane is 1: 1), stirring for 18 hours after ultrasonic uniform dispersion, and obtaining the product after centrifugal separation and drying.
The material is observed by using an ultrasonic diagnostic apparatus, and the material is proved to be used for ultrasonic imaging.
Example 5
The preparation method of the nano metal organic framework cavitation material comprises the following steps:
1) preparing a ferric trichloride solution with the molar concentration of 18mmol/L as a metal source mother solution by taking methanol as a solvent, and preparing a terephthalic acid methanol solution with the molar concentration of 40mmol/L as an organic ligand mother solution by taking methanol as the solvent;
2) respectively taking 10mL of metal source mother liquor and 10mL of organic ligand mother liquor, uniformly mixing, and placing in a 50mL reaction kettle, wherein the molar concentration ratio of the metal source mother liquor to the organic ligand mother liquor in the mixed liquor is 18: 40; placing the reaction kettle in a 50 ℃ oven for reaction for 30 hours, taking out, centrifugally separating, and drying to obtain a dried product;
3) according to the mass ratio of 1: 5, sequentially weighing the tris (pentafluorophenyl) borane and the dried product into a drying conical flask, adding dichloromethane with the same volume (the volume ratio of the added dichloromethane to the tris (pentafluorophenyl) borane is 1: 1), uniformly dispersing by ultrasonic, stirring for 24 hours, and centrifugally separating and drying to obtain the product.
The material is observed by using an ultrasonic diagnostic apparatus, and the material is proved to be used for ultrasonic imaging.
Example 6
The preparation method of the nano metal organic framework cavitation material comprises the following steps:
1) taking dimethyl sulfoxide solution as a solvent, and preparing ferric trichloride solution with the molar concentration of 5mmol/L as metal source mother liquor; similarly, taking dimethyl sulfoxide solution as a solvent, and preparing trimesic acid dimethyl sulfoxide solution with the molar concentration of 20mmol/L as organic ligand mother liquor;
2) respectively taking 10mL of metal source mother liquor and 10mL of organic ligand mother liquor, uniformly mixing, and placing in a 50mL reaction kettle, wherein the molar concentration ratio of the metal source mother liquor to the organic ligand mother liquor in the mixed liquor is 1: 4; placing the reaction kettle in an oven at 70 ℃ for reaction for 30 hours, taking out, centrifugally separating, and drying to obtain a dried product;
3) according to the mass ratio of 1: 2 sequentially weighing perfluorohexyl iodoalkane and a dried product into a drying conical flask, adding dichloromethane with the same volume (the volume ratio of the added dichloromethane to the perfluorohexyl iodoalkane is 1: 1), stirring for 18 hours after ultrasonic uniform dispersion, and obtaining the product after centrifugal separation and drying.
The material is observed by using an ultrasonic diagnostic apparatus, and the material is proved to be used for ultrasonic imaging.
Example 7
In this example, the material of the present invention was tested in the enrichment of mouse tumor sites, and the main experimental steps were as follows:
1) establishing 2 mouse subcutaneous tumor models of human pancreatic cancer cells PANC-1, and respectively injecting 100 mu L of PCN-Fe (III) and PCN-Fe (III) -PFB (5.0mg/mL for PCN-Fe (III)), wherein the PCN-Fe (III) is an organic metal framework material, no cavitation agent active component (cavitation nucleus) is loaded, and the interior is air; PCN-Fe (III) -PFB is loaded with pentafluorobutane (cavitation nuclei) and pentafluorobutane is inside.
2) After 30 minutes, irradiating the tumor part by using an ultrasonic cavitation instrument, and setting the instrument parameters to be 1MHz and 30Wcm in power-2The duty ratio is 50%, the pulse repetition frequency is 100Hz, the peak negative pressure is 0.25MPa, the mechanical index is 0.25, and the time is 20 min; after 24 hours, the cells were analyzed by small animal fluorescence imaging (PerkinElmer, USA) at an excitation of 640nm,and (3) carrying out fluorescence imaging on the small animal under the condition of emission of 710 nm.
Since the fluorescence imaging of the small animal can show the enrichment rate of the tumor part nanoparticles, the strong fluorescence intensity indicates the high enrichment rate, and fig. 4 is a comparison graph of the fluorescence imaging of the small animal of the nano metal organic framework and the PCN-Fe (III) organic metal framework material prepared in example 2; in the figure, a is a fluorescence imaging diagram of the nano metal organic framework prepared in example 2; b is a single PCN-Fe (III) organic metal framework fluorescence imaging picture.
And (4) analyzing results: the enrichment rate of PCN-Fe (III) -PFB loaded with pentafluorobutane (cavitation nucleus) at a mouse tumor part is obviously higher than that of a single PCN-Fe (III) organic metal framework group without the cavitation nucleus, which shows that the cavitation effect formed by ultrasound and the cavitation nucleus can obviously increase the concentration of nanoparticles at the tumor part, and the reason is that the cavitation effect increases the permeability of the tumor part, so that the nanoparticles can be enriched at the tumor part more.
Therefore, the nano metal organic framework cavitation material can be used for cancer cavitation treatment, in particular to breast cancer, pancreatic cancer, renal cancer and liver cancer with thin new blood vessels.
Claims (7)
1. A method for synthesizing a nano metal organic framework cavitation material is characterized by comprising the following steps: the material takes a nano metal organic framework as a carrier and takes a cavitating agent active component as a carried object, and the method comprises the following steps:
1) respectively dissolving a metal source and an organic ligand in a solvent to respectively obtain a metal source mother solution and an organic ligand mother solution; the organic ligand is selected from one of terephthalic acid, 2-aminoterephthalic acid, tetra (4-carboxyphenyl) porphine, 2-nitroterephthalic acid, 2-hydroxyterephthalic acid and trimesic acid, and the metal source is selected from one of tetravalent hafnium ion, tetravalent zirconium ion, ferric ion, divalent copper ion and divalent zinc ion;
2) mixing the metal source mother liquor and the organic ligand mother liquor obtained in the step 1) according to a ratio, heating for reaction, performing centrifugal separation, and drying to obtain a dried product; the heating reaction temperature is 50-90 ℃, and the reaction time is 12-30 hours;
3) dispersing the dried product obtained in the step 2) and a cavitating agent active component in a solvent, stirring, centrifuging, separating and drying, wherein the cavitating agent active component is selected from at least one of 1,1,1,3, 3-pentafluorobutane, perfluorobutane, perfluorohexane, perfluorohexyliodoalkane and tris (pentafluorophenyl) borane.
2. The method for synthesizing the nano metal organic framework cavitation material as claimed in claim 1, wherein: the solvent in the steps 1) and 3) is one or more selected from methanol, ethanol, ethylene glycol, N-dimethylformamide, dichloromethane, trichloromethane, dimethyl sulfoxide and o-dichlorobenzene.
3. The method for synthesizing the nano metal organic framework cavitation material as claimed in claim 2, characterized in that: the molar concentration ratio of the metal source mother liquor to the organic ligand mother liquor in the step 2) is 1: (2-4).
4. The method for synthesizing the nano metal organic framework cavitation material as claimed in claim 3, characterized in that: in the step 3), the mass ratio of the added cavitating agent active component to the dried product is 1: (2-5).
5. The use of the nanometal organic framework cavitation material prepared by the method for synthesizing a nanometal organic framework cavitation material according to claim 1 in the preparation of a medicament for cancer cavitation treatment.
6. The use of the nanometal-organic framework cavitation material according to claim 5 in the preparation of a medicament for cancer cavitation therapy, characterized in that: the cavitation material is firstly enriched at a tumor part through an EPR effect, and liquid-gas phase change occurs after ultrasonic targeted irradiation, so that the cavitation treatment effect is exerted.
7. The use of the nanometal-organic framework cavitation material according to claim 6 in the preparation of a medicament for cancer cavitation therapy, characterized in that: the cancer includes breast cancer, pancreatic cancer, renal cancer, and liver cancer.
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