CN107812191B - A dispersion for chemotherapy, microwave thermotherapy and CT imaging - Google Patents
A dispersion for chemotherapy, microwave thermotherapy and CT imaging Download PDFInfo
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Abstract
The invention discloses a prepared dispersion liquid for chemotherapy, microwave thermotherapy and CT imaging simultaneously, which is prepared by dispersing a zirconium dioxide nano material filled with pagodatree ear polysaccharide in a PBS buffer solution with the preparation concentration range of 0-50mg m L‑1The pH value of the PBS buffer solution is 7.2, or the zirconium dioxide nano material filled with the pagodatree ear polysaccharide is dispersed in the PBS buffer solution to prepare the concentration of 5-20mg m L‑1Wherein the PBS buffer has a pH of 7.2, wherein: the zirconium dioxide nano material is a hollow zirconium dioxide nano material, and is prepared by a sacrificial template method, wherein pagodatree ear polysaccharide is filled in the hollow part of the zirconium dioxide nano material; the particle size of the zirconium dioxide composite nano material is 50-500nm, and the shell thickness is 10-100 nm.
Description
Technical Field
The invention relates to a zirconium dioxide composite nano material and application of the technology in cancer diagnosis and treatment. And more particularly to a dispensing dispersion for simultaneous use in chemotherapy, microwave hyperthermia and CT imaging.
Background
Cancer has become the first leading death disease worldwide. According to the world cancer report of 2014, the worldwide health organization shows that 1400 or more ten thousand new cases of cancer are generated in 2012, 1900 or 2400 ten thousand new cases are generated in 2025, and 2035 shows that the world cancer report of the world health organization is generated. Reports also show that developing countries in africa, asia, and central and south america have the most severe forms of cancer. The incidence rate of malignant tumors in China is also continuously increased, 307 new cancer patients are added in 2012, about 220 people die from the cancers, and the cancer patients account for 21.9% and 26.8% of the total amount of the whole world respectively. Cancer has become the first cause of Death among residents in our country, causing enormous burden and pain to society, families and individuals (Cell Death dis., 2013, 4, 596, chem.soc.rev., 2012, 41, 4306-.
At present, chemotherapy, radiotherapy and surgery are the main means in clinical tumor treatment, but the surgical treatment only aims at local tumor, can rapidly remove primary focus, and is not suitable for tumor of a part difficult to remove; radiotherapy has good curative effect in early cancer stage, poor specificity and easy damage to normal cells; the chemotherapy medicament has great toxic and side effects on human bodies while killing tumor cells. The microwave thermotherapy technology has the advantages of no or minimal invasion, better safety, higher heating temperature in related tissues, larger ablation volume, faster ablation time and more uniform heat flow distribution, and gradually draws attention in the treatment of tumors (Nature Reviews, 2014, 199-. As a non-invasive local heating, the microwave thermotherapy is to perform thermotherapy on tumor by using the heat effect of microwave. When the microwaves enter the biological tissue, they are transmitted and energy absorbed, thereby creating a certain temperature increase in the tissue. When the temperature reaches above 43 ℃, tumor cells can be effectively killed, and the purpose of heat treatment can be further achieved (Cardiovasc. Inter. Rad.2010, 33(4), 818-.
The Chinese patent with the patent application number of 201410453049.2 utilizes the hollow zirconium dioxide nano material to be filled with the ionic liquid with the microwave sensitization performance, and the composite material is successfully applied to the technical fields of tumor CT diagnosis and microwave thermotherapy at the same time, and obtains more satisfactory treatment effect. However, the biological safety of the inner core ionic liquid utilized by the patent needs to be further verified, and the composite structure has two functions of CT imaging and microwave thermotherapy, and does not have a chemotherapy function. In the research of the invention, the sophora fungus polysaccharide used as a chemotherapeutic drug has excellent microwave sensitization performance after being wrapped in the hollow zirconium dioxide, so the sophora fungus polysaccharide can be applied to the field of tumor microwave thermotherapy. Meanwhile, the pagodatree ear polysaccharide is an excellent anti-cancer drug and has chemotherapy performance, so that the pagodatree ear polysaccharide is wrapped in the hollow zirconium dioxide, and the aim of treating tumors by combining chemotherapy and microwave thermotherapy can be fulfilled. According to the invention, the hollow zirconium dioxide has a smaller size, has EPR passive targeting performance in a living body, and can realize the purpose of sustained and controlled release after targeting to a tumor position after wrapping the pagodatree ear polysaccharide, thereby accurately treating tumors. Compared with the material disclosed in patent application No. 201410453049.2, the hollow zirconium dioxide nano material filled with the pagodatree ear polysaccharide has higher biological safety and more obvious CT enhancement effect, integrates chemotherapy, microwave thermotherapy and CT imaging into a whole, and has richer functions.
Clinically, whether accurate diagnosis of tumor is a decisive factor for realizing accurate treatment, and the CT imaging technology as a mature medical image diagnosis means has the advantages of high scanning speed, no overlapping of image tissue structures, clear anatomical relationship, clear image, high density resolution, no wound and pain and the like (J.Nucl.Med.2013, 54(11), 1938-. The invention discovers in research that the hollow zirconium dioxide material has good CT enhancement performance and can be used as a good CT contrast agent, meanwhile, the pagodatree ear polysaccharide used as a chemotherapeutic drug also has good CT enhancement performance, and after the two materials are compounded together, the CT image effect is further enhanced, and the material is expected to become a preferred material for constructing a novel CT contrast agent.
In conclusion, the invention provides a hollow zirconium dioxide composite nano material coated with pagodatree ear polysaccharide and having the functions of microwave sensitization, chemotherapy drug sustained-release and CT imaging, in particular provides a prepared dispersion liquid simultaneously used for chemotherapy, microwave thermotherapy and CT imaging.
Disclosure of Invention
Provides a prepared dispersion liquid for chemotherapy, microwave thermotherapy and CT imaging simultaneously, the dispersion liquid is prepared by dispersing zirconium dioxide nano material filled with pagodatree ear polysaccharide in PBS buffer solution with the preparation concentration range of 0-50mg m L-1The pH value of the PBS buffer solution is 7.2, or the zirconium dioxide nano material filled with the pagodatree ear polysaccharide is dispersed in the PBS buffer solution to prepare the concentration of 5-20mg m L-1Wherein the PBS buffer has a pH of 7.2, wherein: the zirconium dioxide nano material is a hollow zirconium dioxide nano material, and is prepared by a sacrificial template method, wherein pagodatree ear polysaccharide is filled in the hollow part of the zirconium dioxide nano material; the particle size of the zirconium dioxide composite nano material is 50-500nm, and the thickness of a shell layer is 10-100 nm;
preferably, the particle size of the zirconium dioxide nano material is 120-250nm, and the shell thickness is 20-50 nm;
preferably, filling the pagodatree ear polysaccharide comprises the following steps:
1) dispersing sophora japonica ear polysaccharide in a mixed solution consisting of water and an organic solvent, and dispersing uniformly by ultrasonic or stirring to form a sophora japonica ear polysaccharide solution, wherein the mass volume fraction of the sophora japonica ear polysaccharide solution is 1-30%;
2) adding hollow zirconium dioxide nano material into the pagodatree fungus polysaccharide solution obtained in the step 1), wherein the concentration is 1-200mgm L-1Filling the pagodatree ear polysaccharide into the hollow zirconium dioxide nano material by a negative pressure filling method; 3) washing the zirconium dioxide nano material filled with the pagodatree fungus polysaccharide obtained in the step 2) by using deionized water until a supernatant is clear and transparent;
preferably, the solvent in step 1) is selected from one or more of anhydrous ethanol, acetonitrile, DMSO, 1, 4-dioxane, acetone and isopropanol which are soluble in water.
The invention has the following beneficial effects:
1. compared with the prior art, the invention is remarkably different from the prior art in that the pagodatree ear polysaccharide with chemotherapy effect is wrapped by the hollow zirconium dioxide composite nano material, so that the aims of microwave sensitization, chemotherapy drug sustained and controlled release and CT imaging functions can be simultaneously realized, the diagnosis and treatment efficiency is greatly improved, and the invention has good clinical application value.
2. The shell layer zirconium dioxide material and the inner core pagodatree ear polysaccharide of the hollow zirconium dioxide composite nano material with microwave sensitization, chemotherapy drug sustained-release and CT imaging functions have CT image enhancement performance, and after being compounded together, the hollow zirconium dioxide composite nano material can further enhance the CT image effect and can be used as a good CT contrast agent.
3. The sophora fungus polysaccharide-coated hollow zirconium dioxide composite nanomaterial with microwave sensitization, sustained and controlled release of chemotherapeutic drugs and CT imaging functions, disclosed by the invention, has the advantages that the sophora fungus polysaccharide serving as an inner core is a chemotherapeutic traditional Chinese medicine, has an anti-cancer performance and a good microwave sensitization performance, can show a good temperature rise performance under the radiation of a microwave field, and can realize the effect of treating tumors by combining microwave thermotherapy and chemotherapy on tumors.
4. The hollow zirconium dioxide composite nanomaterial wrapping pagodatree fungus polysaccharide and having the functions of microwave sensitization, chemotherapy drug sustained-release and CT imaging, disclosed by the invention, has EPR passive targeting performance due to small size, and can accurately realize the effect of targeted sustained-release of chemotherapy drugs.
Drawings
The following describes embodiments of the present invention in further detail with reference to the accompanying drawings.
Fig. 1 shows a scanning electron microscope photograph of the zirconium dioxide composite nanomaterial with microwave sensitization, sustained/controlled release of chemotherapeutic drugs and CT imaging functions obtained in embodiment 1 of the present invention;
FIG. 2 shows a TEM image of the obtained zirconium dioxide composite nanomaterial with microwave-enhanced, controlled-release and CT imaging functions in example 1 of the present invention;
FIG. 3 shows a dynamic light scattering (D L S) spectrum of the zirconium dioxide composite nanomaterial with microwave sensitization, sustained and controlled release of chemotherapeutic drugs and CT imaging functions obtained in example 1 of the invention, which shows monodispersity thereof;
fig. 4 shows the in vitro microwave heating effect of the zirconium dioxide composite nanomaterial with microwave sensitization, chemotherapy drug sustained-release and CT imaging functions obtained in embodiment 1 of the present invention;
fig. 5 shows the in vitro CT imaging effect of the zirconium dioxide composite nanomaterial with microwave sensitization, chemotherapy drug sustained-release and CT imaging functions and the pure hollow zirconium dioxide material obtained in embodiment 1 of the present invention.
Detailed Description
In order to more clearly illustrate the invention, the invention is further described below with reference to preferred embodiments and the accompanying drawings. Similar parts in the figures are denoted by the same reference numerals. It is to be understood by persons skilled in the art that the following detailed description is illustrative and not restrictive, and is not to be taken as limiting the scope of the invention.
Example 1
(1) Dispersing pagodatree ear polysaccharide in a mixed solution (volume ratio is 1: 1) of deionized water and absolute ethyl alcohol, wherein the mass volume fraction is 1%, and uniformly dispersing by ultrasonic or stirring;
(2) adding the hollow zirconium dioxide composite nano material into the pagodatree fungus polysaccharide aqueous solution obtained in the step 1), wherein the concentration is 5mg m L-1Realizing pagodatree fungus polysaccharide wrapping by a negative pressure filling method;
(3) washing the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide obtained in the step 2) with deionized water until the supernatant is clear and transparent, thus obtaining the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide with the functions of microwave sensitization, chemotherapy drug sustained and controlled release and CT imaging.
It is clearly observed from fig. 1-3 that the obtained hollow zirconium dioxide composite nano-material has uniform distribution, narrow particle size distribution, diameter of 165nm and shell thickness of 25nm, and the obtained material is a hollow structure as is obvious from images of a scanning electron microscope and a transmission electron microscope.
The hollow zirconium dioxide composite nanomaterial coated with pagodatree fungus polysaccharide prepared in the embodiment is used for tumor microwave thermotherapy, and the in-vitro and in-vivo microwave heating experiments and the tumor thermotherapy effect are as follows:
dispersing the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide in PBS buffer solution (pH 7.2) to prepare the hollow zirconium dioxide composite nano material with the concentration of 20mg m L-1The dispersion was placed in an in vitro microwave heating apparatus, and subjected to microwave irradiation, and the control group was treated with an equal volume of PBS buffer (pH 7.2), and the temperature rise results were as shown in fig. 4, which was good in the in vivo animal temperature rise experiment, in which the hollow zirconia composite nanomaterial coated with sophorae polysaccharide was dispersed in PBS buffer (pH 7.2) to prepare a concentration of 5mg m L-1The dispersion was injected into ICR mice inoculated with H22 tumor via tail vein, and the injection dose was 40mg kg-1And after 12 hours, the tumor position is irradiated by microwave, because the hollow zirconium dioxide composite nano material wrapping the pagodatree ear polysaccharide is passively targeted to the tumor position due to the EPR effect, the sustained and controlled release of the pagodatree ear polysaccharide is realized, the local temperature of the tumor can quickly reach over 43 ℃, and the temperature is enough to kill tumor cells. The tumor position is completely recovered about half a month and recovered to be normal
The hollow zirconium dioxide composite nanomaterial coated with pagodatree fungus polysaccharide prepared in the embodiment is used for CT imaging technology, and the in vitro and in vivo imaging processes and effects are as follows:
dispersing the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide in PBS (pH 7.2) to prepare dispersion liquid with different gradient concentrations, wherein the concentration range is 0-50mg m L-1In vitro CT imaging is respectively carried out, the CT value has concentration dependence, the imaging effect and the linear relation are shown in figure 5. the animal in vivo CT imaging experiment process comprises the following steps of dispersing the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide in PBS buffer solution (pH 7.2) to prepare the concentration of 5mg m L-1The dispersion was injected into ICR mice inoculated with H22 tumor via tail vein, and the injection dose was 40mg kg-1In vivo CT imaging is performed at different time periods, and the tumor position has CT enhancement effect.
Example 2
(1) Dispersing pagodatree ear polysaccharide in deionized water and 1, 4-dioxane mixed solution (volume ratio 1: 1) with mass volume fraction of 10%, and ultrasonically or uniformly stirring;
(2) adding the hollow zirconium dioxide composite nano material into the pagodatree fungus polysaccharide aqueous solution obtained in the step 1), wherein the concentration is 10mg m L-1Realizing pagodatree fungus polysaccharide wrapping by a negative pressure filling method;
(3) washing the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide obtained in the step 2) with deionized water until the supernatant is clear and transparent, thus obtaining the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide with the functions of microwave sensitization, chemotherapy drug sustained and controlled release and CT imaging.
The hollow zirconium dioxide composite nanomaterial coated with pagodatree fungus polysaccharide prepared in the embodiment is used for tumor microwave thermotherapy, and the in-vitro and in-vivo microwave heating experiments and the tumor thermotherapy effect are as follows:
dispersing the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide in PBS buffer solution (pH 7.2) to prepare the hollow zirconium dioxide composite nano material with the concentration of 20mg m L-1The dispersion solution of (1) was placed in an in vitro microwave heating apparatus, and subjected to microwave irradiation, and a control group was treated with an equal volume of PBS buffer (pH 7.2), which showed a good heating effect, in an animal in vivo heating experiment, in which a hollow zirconia composite nanomaterial coated with sophorae polysaccharide was dispersed in a PBS buffer (pH 7.2) to prepare a concentration of 5mg m L-1The dispersion was injected into ICR mice inoculated with H22 tumor via tail vein, and the injection dose was 40mg kg-1And after 12 hours, the tumor position is irradiated by microwave, because the hollow zirconium dioxide composite nano material wrapping the pagodatree ear polysaccharide is passively targeted to the tumor position due to the EPR effect, the sustained and controlled release of the pagodatree ear polysaccharide is realized, the local temperature of the tumor can quickly reach over 43 ℃, and the temperature is enough to kill tumor cells. The tumor position is completely recovered about half a month and recovered to be normal
The hollow zirconium dioxide composite nanomaterial coated with pagodatree fungus polysaccharide prepared in the embodiment is used for CT imaging technology, and the in vitro and in vivo imaging processes and effects are as follows:
dispersing the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide in PBS (pH 7.2) to prepare dispersion liquid with different gradient concentrations, wherein the concentration range is 0-50mg m L-1Separately, in vitroThe CT value has concentration dependence, and the experiment process of in vivo animal CT imaging comprises dispersing hollow zirconium dioxide composite nanometer material coated with pagodatree ear polysaccharide in PBS buffer solution (pH 7.2) to obtain 5mg m L-1The dispersion was injected into ICR mice inoculated with H22 tumor via tail vein, and the injection dose was 40mg kg-1In vivo CT imaging is performed at different time periods, and the tumor position has CT enhancement effect.
Example 3
(1) Dispersing pagodatree ear polysaccharide in deionized water with the mass volume fraction of 30 percent, and dispersing uniformly by ultrasonic or stirring;
(2) adding the hollow zirconium dioxide composite nano material into the pagodatree fungus polysaccharide aqueous solution obtained in the step 1), wherein the concentration is 100mg m L-1Realizing pagodatree fungus polysaccharide wrapping by a negative pressure filling method;
(3) washing the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide obtained in the step 2) with deionized water until the supernatant is clear and transparent, thus obtaining the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide with the functions of microwave sensitization, chemotherapy drug sustained and controlled release and CT imaging.
The hollow zirconium dioxide composite nanomaterial coated with pagodatree fungus polysaccharide prepared in the embodiment is used for tumor microwave thermotherapy, and the in-vitro and in-vivo microwave heating experiments and the tumor thermotherapy effect are as follows:
dispersing the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide in PBS buffer solution (pH 7.2) to prepare the hollow zirconium dioxide composite nano material with the concentration of 20mg m L-1The dispersion solution of (1) was placed in an in vitro microwave heating apparatus, and subjected to microwave irradiation, and a control group was treated with an equal volume of PBS buffer (pH 7.2), which showed a good heating effect, in an animal in vivo heating experiment, in which a hollow zirconia composite nanomaterial coated with sophorae polysaccharide was dispersed in a PBS buffer (pH 7.2) to prepare a concentration of 5mg m L-1The dispersion was injected into ICR mice inoculated with H22 tumor via tail vein, and the injection dose was 40mg kg-1And after 12 hours, the tumor position is irradiated by microwave, and the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide is passively targeted to the tumor due to the EPR effectThe position and the sustained and controlled release of the pagodatree ear polysaccharide are realized, the local temperature of the tumor can quickly reach over 43 ℃, and the temperature is enough to kill tumor cells. The tumor position is completely recovered about half a month and recovered to be normal
The hollow zirconium dioxide composite nanomaterial coated with pagodatree fungus polysaccharide prepared in the embodiment is used for CT imaging technology, and the in vitro and in vivo imaging processes and effects are as follows:
dispersing the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide in PBS (pH 7.2) to prepare dispersion liquid with different gradient concentrations, wherein the concentration range is 0-50mg m L-1The in vivo animal CT imaging experiment process includes dispersing the composite nanometer hollow zirconium dioxide material coated with pagodatree ear polysaccharide in PBS buffer solution (pH 7.2) to prepare concentration of 5mg m L-1The dispersion was injected into ICR mice inoculated with H22 tumor via tail vein, and the injection dose was 40mg kg-1In vivo CT imaging is performed at different time periods, and the tumor position has CT enhancement effect.
Example 4
(1) Dispersing pagodatree ear polysaccharide in a mixed solution of deionized water and acetone, wherein the mass volume fraction is 20%, and uniformly dispersing by ultrasonic or stirring;
(2) adding the hollow zirconium dioxide composite nano material into the pagodatree fungus polysaccharide aqueous solution obtained in the step 1), wherein the concentration is 200mg m L-1Realizing pagodatree fungus polysaccharide wrapping by a negative pressure filling method;
(3) washing the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide obtained in the step 2) with deionized water until the supernatant is clear and transparent, thus obtaining the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide with the functions of microwave sensitization, chemotherapy drug sustained and controlled release and CT imaging.
The hollow zirconium dioxide composite nanomaterial coated with pagodatree fungus polysaccharide prepared in the embodiment is used for tumor microwave thermotherapy, and the in-vitro and in-vivo microwave heating experiments and the tumor thermotherapy effect are as follows:
dispersing the hollow zirconium dioxide composite nano material coated with pagodatree ear polysaccharide inIn PBS buffer (pH 7.2), the concentration was 20mg m L-1The dispersion solution of (1) was placed in an in vitro microwave heating apparatus, and subjected to microwave irradiation, and a control group was treated with an equal volume of PBS buffer (pH 7.2), which showed a good heating effect, in an animal in vivo heating experiment, in which a hollow zirconia composite nanomaterial coated with sophorae polysaccharide was dispersed in a PBS buffer (pH 7.2) to prepare a concentration of 5mg m L-1The dispersion was injected into ICR mice inoculated with H22 tumor via tail vein, and the injection dose was 40mg kg-1And after 12 hours, the tumor position is irradiated by microwave, because the hollow zirconium dioxide composite nano material wrapping the pagodatree ear polysaccharide is passively targeted to the tumor position due to the EPR effect, the sustained and controlled release of the pagodatree ear polysaccharide is realized, the local temperature of the tumor can quickly reach over 43 ℃, and the temperature is enough to kill tumor cells. The tumor position is completely recovered about half a month and recovered to be normal
The hollow zirconium dioxide composite nanomaterial coated with pagodatree fungus polysaccharide prepared in the embodiment is used for CT imaging technology, and the in vitro and in vivo imaging processes and effects are as follows:
dispersing the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide in PBS (pH 7.2) to prepare dispersion liquid with different gradient concentrations, wherein the concentration range is 0-50mg m L-1The in vivo animal CT imaging experiment process includes dispersing the composite nanometer hollow zirconium dioxide material coated with pagodatree ear polysaccharide in PBS buffer solution (pH 7.2) to prepare concentration of 5mg m L-1The dispersion was injected into ICR mice inoculated with H22 tumor via tail vein, and the injection dose was 40mg kg-1In vivo CT imaging is performed at different time periods, and the tumor position has CT enhancement effect.
Example 5
(1) Dispersing pagodatree ear polysaccharide in a mixed solution of deionized water and isopropanol, wherein the mass volume fraction is 15%, and uniformly dispersing by ultrasonic or stirring;
(2) adding the hollow zirconium dioxide composite nano material into the pagodatree fungus polysaccharide aqueous solution obtained in the step 1), wherein the concentration is 50mg m L-1The pagodatree fungus polysaccharide is wrapped by a negative pressure filling method；
(3) Washing the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide obtained in the step 2) with deionized water until the supernatant is clear and transparent, thus obtaining the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide with the functions of microwave sensitization, chemotherapy drug sustained and controlled release and CT imaging.
The hollow zirconium dioxide composite nanomaterial coated with pagodatree fungus polysaccharide prepared in the embodiment is used for tumor microwave thermotherapy, and the in-vitro and in-vivo microwave heating experiments and the tumor thermotherapy effect are as follows:
dispersing the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide in PBS buffer solution (pH 7.2) to prepare the hollow zirconium dioxide composite nano material with the concentration of 20mg m L-1The dispersion solution of (1) was placed in an in vitro microwave heating apparatus, and subjected to microwave irradiation, and a control group was treated with an equal volume of PBS buffer (pH 7.2), which showed a good heating effect, in an animal in vivo heating experiment, in which a hollow zirconia composite nanomaterial coated with sophorae polysaccharide was dispersed in a PBS buffer (pH 7.2) to prepare a concentration of 5mg m L-1The dispersion was injected into ICR mice inoculated with H22 tumor via tail vein, and the injection dose was 40mg kg-1And after 12 hours, the tumor position is irradiated by microwave, because the hollow zirconium dioxide composite nano material wrapping the pagodatree ear polysaccharide is passively targeted to the tumor position due to the EPR effect, the sustained and controlled release of the pagodatree ear polysaccharide is realized, the local temperature of the tumor can quickly reach over 43 ℃, and the temperature is enough to kill tumor cells. The tumor position is completely recovered about half a month and recovered to be normal
The hollow zirconium dioxide composite nanomaterial coated with pagodatree fungus polysaccharide prepared in the embodiment is used for CT imaging technology, and the in vitro and in vivo imaging processes and effects are as follows:
dispersing the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide in PBS (pH 7.2) to prepare dispersion liquid with different gradient concentrations, wherein the concentration range is 0-50mg m L-1And respectively carrying out in-vitro CT imaging, wherein the CT value has concentration dependence. The experimental process of in vivo CT imaging of animals is as follows: dispersing the hollow zirconium dioxide composite nano material coated with the pagodatree ear polysaccharide in a PBS (pH 7.2),the preparation concentration is 5mg m L-1The dispersion was injected into ICR mice inoculated with H22 tumor via tail vein, and the injection dose was 40mg kg-1In vivo CT imaging is performed at different time periods, and the tumor position has CT enhancement effect.
Examples 6 to 10
The difference is that the absolute ethanol used in the step (1) is replaced by one or a mixture of acetonitrile, DMSO, 1, 4-dioxane, acetone and isopropanol, and the result is similar to that of the example 1.
It should be understood that the above-mentioned embodiments of the present invention are only examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention, and it will be obvious to those skilled in the art that other variations or modifications may be made on the basis of the above description, and all embodiments may not be exhaustive, and all obvious variations or modifications may be included within the scope of the present invention.
Claims (4)
1. A dispersion for chemotherapy, microwave thermotherapy and CT imaging is prepared by dispersing nanometer zirconium dioxide material filled with pagodatree ear polysaccharide in PBS buffer solution at a concentration of 5-20mg m L-1Wherein the PBS buffer has a pH of 7.2, wherein: the zirconium dioxide nano material is a hollow zirconium dioxide nano material, and is prepared by a sacrificial template method, wherein pagodatree ear polysaccharide is filled in the hollow part of the zirconium dioxide nano material; the particle size of the zirconium dioxide composite nano material is 50-500nm, and the shell thickness is 10-100 nm.
2. The dispensing dispersion of claim 1, wherein: the particle size of the zirconium dioxide nano material is 120-250nm, and the shell thickness is 20-50 nm.
3. The formulated dispersion of claim 1 or 2, wherein filling the pagodatree ear polysaccharide comprises the steps of:
1) dispersing sophora japonica ear polysaccharide in a mixed solution consisting of water and an organic solvent, and dispersing uniformly by ultrasonic or stirring to form a sophora japonica ear polysaccharide solution, wherein the mass volume fraction of the sophora japonica ear polysaccharide solution is 1-30%;
2) adding hollow zirconium dioxide nano material into the pagodatree fungus polysaccharide solution obtained in the step 1), wherein the concentration is 1-200mg m L-1Filling the pagodatree ear polysaccharide into the hollow zirconium dioxide nano material by a negative pressure filling method;
3) washing the zirconium dioxide nano material filled with the pagodatree fungus polysaccharide obtained in the step 2) by using deionized water until a supernatant is clear and transparent.
4. The dispensing dispersion of claim 3, wherein: the solvent in the step 1) is one or more selected from water-soluble absolute ethyl alcohol, acetonitrile, DMSO, 1, 4-dioxane, acetone and isopropanol.
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| CN109806400B (en) * | 2019-03-18 | 2022-03-18 | 中国医科大学附属第一医院 | Mesoporous nano zirconium dioxide drug-loaded material, preparation method thereof and sustained and controlled release drug |
| CN110257070B (en) * | 2019-04-28 | 2022-03-04 | 中国科学院理化技术研究所 | Hollow zirconia @ quantum dot composite ball and preparation method and application thereof |
| CN110548173B (en) * | 2019-08-26 | 2021-10-26 | 苏州恒瑞迦俐生生物医药科技有限公司 | Preparation method of chemoembolization microsphere with microwave sensitization effect |
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| CN104888216B (en) | 2017-12-15 |
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