CN111956617B - Targeting microsphere with long-acting anti-tumor characteristic and preparation method thereof - Google Patents
Targeting microsphere with long-acting anti-tumor characteristic and preparation method thereof Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/34—Copper; Compounds thereof
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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
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P35/00—Antineoplastic agents
Abstract
The invention relates to the medical and sanitary field, in particular to a targeting microsphere with long-acting anti-tumor property and a preparation method thereof, which is a therapeutic drug for targeting treatment of tumors of all parts in vivo and has the characteristics of efficiently killing tumor cells and inhibiting tumor amplification. Adding or covering the surface of the targeting microsphere substrate with a functional substance capable of generating oxygen free radicals or hydroxyl free radicals, wherein the functional substance is a copper-containing material and can generate active oxygen substances. Copper ions with an anti-tumor function and a photocatalyst material are introduced into the targeted drug, so that the long-acting anti-tumor performance is realized, and the problems of poor selectivity of the existing targeted drug on tumor cells and normal cells and the like are solved. Copper ions, photocatalyst materials and drug carriers are prepared into targeted micro-nano particles by utilizing electrostatic spinning equipment, and the targeted micro-nano particles are applied to pathological change parts by adopting a traditional targeted drug delivery mode. The long-acting anti-tumor targeting microsphere can reduce the tumor recurrence probability and reduce the economic burden in the medical and sanitary fields.
Description
Technical Field
The invention relates to the medical and sanitary field, in particular to a targeting microsphere with long-acting anti-tumor property and a preparation method thereof, which is a therapeutic drug for targeting treatment of tumors of all parts in vivo and has the characteristics of efficiently killing tumor cells and inhibiting tumor amplification.
Background
With the increasing prominence of the problems of diet safety, environmental pollution and the like, the number of people suffering from cancer is increasing, and the trend of the ill people is towards the younger trend. At present, the most widely used anti-tumor means in clinical application is the combination of chemotherapy, radiotherapy and radiotherapy. These treatments cause many side effects to the human body, such as physical weakness, immune function reduction, bone marrow suppression, digestive disorder, toxicity in various large organs, etc. Photodynamic therapy (PDT) is an emerging modalityThe therapeutic modalities, in clinical practice, show unique advantages for the treatment of a variety of cancer indications. From the principle, PDT is a light-mediated therapy that relies on a special light-activated agent, called Photosensitizer (PS), that exerts critical cellular/vascular toxicity through light-mediated generation of Reactive Oxygen Species (ROS) in the tumor microenvironment. PDT has received increasing attention in tumor therapy in recent decades, both in terms of its highly adjustable parameters and in terms of clinically proven therapeutic efficacy. However, most of the existing photosensitizers must be excited by ultraviolet light to initiate photochemical reactions, which may increase the risk of ultraviolet-related side effects, reducing the clinical usefulness of PDT. In contrast, near infrared light is less phototoxic than ultraviolet or visible light, due to deeper tissue penetration by near infrared light in physiological environments. Therefore, the substance can be excited under near infrared, so that the substance generating active oxygen has more clinical application value. The chemical kinetic therapy (CDT) takes weak acidity of microenvironment in tumor focus area as reaction condition and over-expressed H 2 O 2 The transition metal nano material is used as a catalyst to initiate Fenton or Fenton-like reaction in the tumor cells to catalyze H 2 O 2 Generates active species with strong oxidizability such as hydroxyl free radical (. OH) and the like, induces apoptosis of tumor cells, and is a novel tumor treatment technology.
Disclosure of Invention
The invention aims to provide a targeting microsphere with long-acting anti-tumor property and a preparation method thereof, which utilize the principles of chemical kinetics and photodynamic to introduce copper ions with anti-tumor function and photocatalyst materials into a targeting medicament, realize the function of high-efficiency and long-lasting anti-tumor, and solve the problems of poor selectivity of the existing targeting medicament on tumor cells and normal cells, and the like.
The technical scheme of the invention is as follows:
a targeting microsphere with long-acting anti-tumor property is characterized in that a functional substance capable of generating oxygen free radicals or hydroxyl free radicals is added to or covered on the surface of a targeting microsphere substrate, and the functional substance is a copper-containing material and a substance capable of generating Reactive Oxygen Species (ROS).
In the functional substance, the copper-containing material and the substance capable of generating active oxygen are dispersed in the targeted microsphere base material in a physical blending mode or combined on the surface of the targeted microsphere base material through chemical bonding or electrostatic action, and the copper-containing material and the substance capable of generating active oxygen are compatible with the targeted microsphere base material.
The targeted microsphere with long-acting anti-tumor property comprises the following components in percentage by weight: the copper-containing material is in the range of 1 to 50 mole percent, and the active oxygen species can be generated in the range of 1 to 50 mole percent, with the balance being a water-absorbing polymeric material that is all components other than the two functional materials described above.
The copper-containing material is one or two of a divalent copper salt and a copper-carrying polymer, the copper-carrying polymer is formed by chemically bonding divalent copper ions to polymer micromolecules, the copper-containing material is uniformly distributed in the targeting microsphere in a metal-polymer chain segment form or in a metal inorganic salt form, and at the moment, the size of the copper-containing inorganic salt is in the range of 100 nm-10 mu m.
According to the targeting microsphere with the long-acting anti-tumor characteristic, the polymer micromolecules with divalent copper ions capable of being chemically bonded are one or more than two of chitosan oligosaccharide, alginate, amino acid, starch, cyclodextrin, cellulose, collagen, micromolecule protein, polyalcohol, amines and polyesters, and the divalent copper salt is one or more than two of basic copper sulfate, copper chloride, copper hydroxide, copper acetate, copper amino acid and copper quinoline.
The targeting microsphere with the long-acting anti-tumor characteristic can generate active oxygen substances as infrared photocatalyst materials, and the infrared photocatalyst materials are one or more than two of perovskite, molybdenum disulfide, cadmium sulfide and cadmium stannide, but not limited to the materials.
The targeting microsphere substrate is a drug microsphere for treating liver cancer, gastric cancer, lung cancer, gallbladder cancer, bone cancer or intravascular malignant tumor.
The preparation method of the targeting microsphere with long-acting anti-tumor property comprises the following steps:
the method comprises the following steps: preparing a solution of a copper-containing material;
step two: adding a material capable of generating active oxygen into a solution containing a copper-containing material to prepare a targeted microsphere polymer mother liquor containing the copper-containing material and the material capable of generating active oxygen;
step three: the targeted microsphere polymer mother solution with the anti-tumor characteristic is processed into targeted microspheres by adopting an emulsion method, a spraying method or an electrostatic spraying method, and the particle size of the dried targeted microspheres is 10 nm-100 mu m.
In the first step, when the copper-containing material is a copper-carrying polymer, a chemical grafting method is adopted to prepare a solution of the copper-containing material, and the preparation method comprises the following steps:
(1) Preparing a copper salt aqueous solution with the mass volume concentration of 1-200 mg/mL;
(2) Preparing a micromolecular polymer matrix solution with the mass volume concentration of 5-1000 mg/mL, wherein the solvent is an organic solvent, and the type of the organic solvent is determined according to the characteristics of the adopted polymer matrix;
(3) Adding a copper salt aqueous solution into a micromolecular polymer matrix solution, wherein the mass ratio of the copper salt aqueous solution to the micromolecular polymer matrix solution is 1:1 to 1:10, fully stirring and reacting for 1-24 hours to obtain the copper-containing material solution.
In the second step of the preparation method of the targeting microsphere with the long-acting anti-tumor characteristic, the molar ratio of the active oxygen material to the copper-containing material is 1:10 to 10:1, uniformly suspending the active oxygen generating material in a solution containing copper material by mechanical stirring or magnetic stirring for 1-10 hours to form a targeting microsphere polymer mother solution with anti-tumor property.
The design idea of the invention is as follows:
in the process of researching the antibacterial and antiviral effects of copper ions and cuprous compounds, the divalent copper ions have the bactericidal effect because the bacteria can metabolize under the aerobic conditionGenerating reactive oxygen species (ROS, e.g. superoxide anion radical O) 2 · – ) And hydrogen peroxide (H) 2 O 2 ) The divalent copper ions can generate a series of reactions in succession to generate hydroxyl free radicals (OH) with strong oxidizing property, so as to play a role in sterilization, and the action principle is also applicable to the anti-tumor action, and the reaction formula is as follows:
Cu 2+ +O 2 · - ＝Cu + +O 2 (1)
Cu + +H 2 O 2 di Cu 2+ +OH - +·OH (2)
H 2 O 2 +O 2 · - Di O 2 +OH - +·OH (3)
The proliferation process of tumor cells can generate weak acid environment and hydrogen peroxide, and divalent copper ions are used for resisting tumors by utilizing the chemical kinetics principle. As shown in figures 1, 2 and 3, the invention designs an anti-tumor targeting microsphere (figures 1 and 3) containing copper ions and a compound (material with photocatalyst characteristic) capable of generating ROS, and further compounds the anti-tumor targeting microsphere with a drug carrier, takes infrared illumination as an anti-tumor 'switch', artificially increases the amount of ROS participating in reaction, skillfully combines the chemical kinetics principle and the photodynamic principle, and can achieve the treatment effect which cannot be achieved by a single method, thereby realizing the high-efficiency and lasting anti-tumor function.
The invention has the characteristics and beneficial effects that:
1. the efficient and durable anti-tumor targeting microsphere is prepared by matching a compound containing copper ions and a compound capable of generating ROS, and compounding the compound into a microsphere carrier, so that the efficient and durable anti-tumor effect is realized.
2. The long-acting killing of tumor cells utilizes the continuous existence of copper ions and photocatalyst nano powder capable of generating active oxygen in microspheres, ROS is continuously generated under the illumination condition, and the ROS and the copper ions react under the weak acid condition to produce substances with strong oxidizing property so as to kill the tumor cells. In addition, copper ions and nano powder are not consumed in the reaction, so that a long-acting anti-tumor effect can be realized.
3. The targeted microsphere is different from the traditional targeted drug-loaded microsphere which carries the chemotherapeutic drugs essentially, trace element ions and photocatalyst inorganic materials which exist in a human body in a large amount are used for replacing the chemotherapeutic drugs with larger adverse reactions and rays with the radiation function, and a new way for resisting tumors is opened up.
4. The long-acting anti-tumor targeting microsphere can reduce the tumor recurrence probability and reduce the economic burden in the medical and sanitary fields.
Drawings
FIG. 1 is a schematic of a targeted microsphere topography.
FIG. 2 is a schematic view of the biological functionalization of targeted microspheres with long-lasting anti-tumor effect.
FIG. 3 is a schematic diagram of the internal structure of a targeting microsphere with long-acting anti-tumor effect.
Detailed Description
In the specific implementation process, fig. 2 and 3 show the general idea of the invention. The invention utilizes electrostatic spinning equipment to prepare targeted microspheres from copper ions, photocatalyst materials and drug polymer carriers, and the targeted microspheres comprise the following components: the copper-containing material is in the range of 1% to 50% (preferably 2% to 10%) by mole, the active oxygen species can be generated in the range of 1% to 50% (preferably 2% to 10%) by mole, and the balance is a polymeric material having water absorption properties, which is all components except the above two functional materials. The copper-containing material is one or two of a cupric salt and a copper-carrying polymer, the copper-carrying polymer is formed by chemically bonding cupric ions to polymer small molecules, the copper-containing material is uniformly distributed in the targeting microsphere in a metal-polymer chain segment mode or in a metal inorganic salt mode, and the size of the copper-containing inorganic salt ranges from 100nm to 10 mu m (preferably 100nm to 1 mu m). The traditional targeted drug delivery mode is adopted to be applied to the lesion part. The long-acting anti-tumor targeting microsphere can reduce the tumor recurrence probability and reduce the economic burden in the medical and sanitary fields.
The present invention will be explained in further detail below by way of examples and figures.
Example 1:
first, a solution of copper-containing material is prepared:
(1) Preparing a copper sulfate aqueous solution with the mass volume concentration of 10 mg/mL;
(2) Dissolving a micromolecular chitosan oligosaccharide polymer in 1wt% acetic acid aqueous solution to prepare micromolecular chitosan oligosaccharide polymer matrix solution with mass volume concentration of 50 mg/mL;
(3) Adding a copper sulfate aqueous solution into a micromolecular chitosan oligosaccharide polymer matrix solution, wherein the mass ratio of the copper sulfate aqueous solution to the micromolecular chitosan oligosaccharide polymer matrix solution is 1:2, fully stirring and reacting for 12 hours to obtain the copper-containing material solution.
Secondly, a stock solution of a material that can generate active oxygen under certain conditions is prepared:
adding molybdenum disulfide into a solution containing a copper material according to a molar ratio of 1.
Finally, preparing the antitumor targeting microspheres:
preparing targeted microspheres from the targeted microsphere polymer mother liquor with the anti-tumor characteristic by electrostatic spraying by using electrostatic spinning equipment, and drying to obtain the targeted microspheres with the long-acting anti-tumor effect (shown in figure 1), wherein the particle size of the targeted microspheres is 50-100 nm.
In the targeting microsphere with long-acting anti-tumor property, the mole percentage of the copper-containing material is 10%, the mole percentage of the active oxygen species can be generated is 10%, and the balance is the water-absorbing shell oligosaccharide-based polymer material.
Comparative example 1:
1. preparation of a solution of copper-containing material:
(1) Preparing a copper sulfate aqueous solution with the mass volume concentration of 10 mg/mL;
(2) Dissolving a micromolecular chitosan oligosaccharide polymer in 1wt% acetic acid aqueous solution to prepare micromolecular chitosan oligosaccharide polymer matrix solution with mass volume concentration of 50 mg/mL;
(3) Adding the copper sulfate aqueous solution into the micromolecular chitosan oligosaccharide polymer matrix solution, fully stirring and reacting for 12 hours to obtain the solution containing the copper material.
2. And (3) preparing the copper-carrying microspheres.
Preparing the microspheres from the solution containing the copper material by electrostatic spraying by using electrostatic spinning equipment, and drying to obtain the copper-loaded targeted microspheres with the particle size of 50-100 nm.
Comparative example 2:
1. preparing a stock solution of a material that can generate active oxygen under certain conditions:
(1) Dissolving a micromolecular chitosan oligosaccharide polymer in 1wt% acetic acid aqueous solution to prepare micromolecular chitosan oligosaccharide polymer matrix solution with mass volume concentration of 50 mg/mL;
(2) Adding molybdenum disulfide into a micromolecular chitosan oligosaccharide polymer matrix solution, wherein the mass ratio of the molybdenum disulfide is 5%, and mechanically stirring or magnetically stirring for 2 hours to uniformly suspend the molybdenum disulfide in the polymer solution to form a photocatalyst-loaded microsphere preparation solution.
2. Preparing microspheres which are purely loaded with photocatalyst:
preparing the microsphere by electrostatic spraying the photocatalyst-carrying solution by electrostatic spinning equipment, and drying to obtain the photocatalyst-carrying targeted microsphere with the particle size of 50-100 nm.
The microspheres prepared in example 1, comparative example 1 and comparative example 2 were co-cultured with liver cancer cells, and infrared light was applied thereto in stages during the culture. And co-culturing for the same period of time, and observing the proliferation condition and the morphology of the cells. The results show that only liver cancer cells co-cultured with the microspheres of the group 1 in the example for 24 hours undergo a great amount of apoptosis, the apoptosis rate reaches over 80 percent, and the apoptosis rate of liver cancer cells of other experimental groups is far lower than that of the group 1 in the example although the liver cancer cells undergo apoptosis to a certain degree. The experimental results and analysis show that the novel long-acting anti-tumor targeting microsphere and the preparation method thereof show outstanding anti-tumor function and have obvious beneficial effects.
Example 2:
first, a solution of copper-containing material is prepared:
(1) Preparing a copper chloride aqueous solution with the mass volume concentration of 100 mg/mL;
(2) Dissolving a micromolecular sodium alginate polymer in 1wt% acetic acid aqueous solution to prepare micromolecular sodium alginate polymer matrix solution with mass volume concentration of 100 mg/mL;
(3) Adding a copper chloride aqueous solution into a micromolecular sodium alginate polymer matrix solution, wherein the mass ratio of the copper chloride aqueous solution to the micromolecular sodium alginate polymer matrix solution is 1:2, fully stirring and reacting for 12 hours to obtain the copper-containing material solution.
Secondly, a stock solution of a material that can generate active oxygen under certain conditions is prepared:
adding the perovskite into a solution containing a copper material according to a molar ratio of 4 to copper chloride of 1, and uniformly suspending the perovskite in the solution containing the copper material by mechanical stirring or magnetic stirring for 2 hours to form a targeting microsphere polymer mother solution with anti-tumor characteristics.
Finally, preparing the antitumor targeting microspheres:
the targeted microsphere polymer mother liquor with the anti-tumor characteristic is prepared into the targeted microsphere by electrostatic spraying by adopting electrostatic spinning equipment, and the targeted microsphere with the long-acting anti-tumor effect is obtained after drying (see figure 1), wherein the particle size of the targeted microsphere polymer mother liquor is 10-50 mu m.
In the targeting microsphere with long-acting anti-tumor property, the mole percentage of the copper-containing material is 5%, the mole percentage of the active oxygen substance can be generated is 20%, and the rest is the water-absorbing sodium alginate cross-linked polymer material.
The microspheres prepared in example 2 were co-cultured with lung cancer cells, and during the culture, infrared light was applied in stages. And co-culturing for the same period of time, and observing the proliferation condition and the morphology of the cells. The results show that only lung cancer cells co-cultured with the microspheres of the group in the example 2 for 24 hours undergo a great amount of apoptosis, the apoptosis rate reaches over 80 percent, and the liver cancer cells of other comparative experiment groups with the same size undergo apoptosis to a certain degree, but the apoptosis rate is far lower than that of the group in the example 2.
Example 3:
first, a solution of copper-containing material is prepared:
(1) Preparing a copper acetate aqueous solution with the mass volume concentration of 20 mg/mL;
(2) Dissolving a micromolecular cyclodextrin polymer in 1wt% acetic acid aqueous solution to prepare micromolecular cyclodextrin polymer matrix solution with mass volume concentration of 20 mg/mL;
(3) Adding a copper acetate aqueous solution into a micromolecular cyclodextrin polymer matrix solution, wherein the mass ratio of the copper acetate aqueous solution to the micromolecular cyclodextrin polymer matrix solution is 1:4, fully stirring and reacting for 12 hours to obtain the copper-containing material solution.
Secondly, a stock solution of a material that can generate active oxygen under certain conditions is prepared:
adding the perovskite into a solution containing a copper material according to the molar ratio of 1:10 to copper acetate, and uniformly suspending the perovskite in the solution containing the copper material by mechanical stirring or magnetic stirring for 2 hours to form a targeted microsphere polymer mother solution with anti-tumor characteristics.
Finally, preparation of the antitumor targeting microsphere:
preparing targeted microspheres from the targeted microsphere polymer mother liquor with the anti-tumor characteristic by electrostatic spraying by using electrostatic spinning equipment, and drying to obtain the targeted microspheres with the long-acting anti-tumor effect (see figure 1), wherein the particle size of the targeted microspheres is 1-20 microns.
In the targeting microsphere with long-acting anti-tumor property, the mole percentage of the copper-containing material is 4%, the mole percentage of the active oxygen species can be generated is 40%, and the rest is the cyclodextrin cross-linked polymer material with water absorption property.
The microspheres prepared in example 3 were co-cultured with hepatoma cells, and infrared light was applied in stages during the culture. And co-culturing for the same period of time, and observing the proliferation condition and the morphology of the cells. The results show that only liver cancer cells co-cultured with the microspheres of the group 3 for 24 hours in the example are subjected to massive apoptosis, the apoptosis rate reaches over 90 percent, and the apoptosis rate of other liver cancer cells of the control experiment group with the same size is far lower than that of the group 3 in the example although the liver cancer cells are also subjected to apoptosis to a certain degree.
Claims (5)
1. A targeting microsphere with long-acting anti-tumor property is characterized in that a functional substance capable of generating oxygen free radicals or hydroxyl free radicals is added to or covered on the surface of a targeting microsphere substrate, and the functional substance is a copper-containing material and a substance capable of generating active oxygen;
in the functional substance, the copper-containing material and the substance capable of generating active oxygen are dispersed in the targeted microsphere base material in a physical blending mode or combined on the surface of the targeted microsphere base material through chemical bonding or electrostatic action, and both the copper-containing material and the substance capable of generating active oxygen have compatibility with the targeted microsphere base material;
the composition of the targeting microsphere is as follows: the copper-containing material is in a molar percentage of 1-50%, the molar percentage of active oxygen substances can be generated in a molar percentage of 1-50%, and the balance is a water-absorbing polymer material which is all components except the two functional materials;
the copper-containing material is one or two of a cupric salt and a copper-carrying polymer, the copper-carrying polymer is formed by chemically bonding a cupric ion to a polymer micromolecule, the copper-containing material is uniformly distributed in the targeting microsphere in a metal-polymer chain segment form or in a metal inorganic salt form, and at the moment, the size of the copper-containing inorganic salt is within the range of 100nm to 10 mu m;
the polymer micromolecules with divalent copper ions capable of being chemically bonded are one or more than two of chitosan oligosaccharide, alginate, amino acid, starch, cyclodextrin, cellulose, collagen, micromolecular protein, polyalcohol, amine and polyester, and the divalent copper salt is one or more than two of basic copper sulfate, copper chloride, copper hydroxide, copper acetate, copper amino acid and copper quinoline;
the active oxygen substance can be generated by infrared photocatalyst material, and the infrared photocatalyst material is one or more than two of perovskite, molybdenum disulfide, cadmium sulfide and cadmium stannide.
2. The targeted microsphere with long-acting anti-tumor property according to claim 1, wherein the targeted microsphere substrate is a drug microsphere for treating liver cancer, gastric cancer, lung cancer, gallbladder cancer, bone cancer or intravascular malignant tumor.
3. A method for preparing the targeting microsphere with long-acting anti-tumor property according to claim 1, which comprises the following steps:
the method comprises the following steps: preparing a solution of a copper-bearing material;
step two: adding a material capable of generating active oxygen into a solution containing a copper-containing material to prepare a targeted microsphere polymer mother liquor containing the copper-containing material and the material capable of generating active oxygen;
step three: processing the targeting microsphere polymer mother solution with the anti-tumor characteristic into targeting microspheres by adopting an emulsion method, a spraying method or an electrostatic spraying method, wherein the particle size of the dried targeting microspheres is 10nm to 100 mu m.
4. The method for preparing targeted microspheres with long-acting anti-tumor property as claimed in claim 3, wherein in the step one, when the copper-containing material is a copper-loaded polymer, a chemical grafting method is adopted to prepare a solution of the copper-containing material, and the method comprises the following steps:
(1) Preparing a copper salt aqueous solution with the mass volume concentration of 1 to 200mg/mL;
(2) Preparing a small molecular polymer matrix solution with the mass volume concentration of 5-1000mg/mL, wherein the solvent is an organic solvent, and the type of the organic solvent is determined according to the characteristics of the adopted polymer matrix;
(3) Adding a copper salt aqueous solution into a micromolecular polymer matrix solution, wherein the mass ratio of the copper salt aqueous solution to the micromolecular polymer matrix solution is 1:1 to 1: and 10, fully stirring and reacting for 1-24 hours to obtain a copper-containing material solution.
5. The method for preparing targeted microspheres with long-acting anti-tumor properties according to claim 3, wherein in the second step, the molar ratio of the active oxygen material to the copper-containing material is 1:10 to 10:1, uniformly suspending the material capable of generating active oxygen in a solution containing a copper material by mechanical stirring or magnetic stirring for 1 to 10 hours to form a targeting microsphere polymer mother solution with the anti-tumor property.
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|---|
| Glutathione Depletion in a Benign Manner by MoS2-Based Nanoflowers for Enhanced Hypoxia-Irrelevant Free-Radical-Based Cancer Therapy;Si Wu等;《Small》;20191121(第15期);第1-10页 * |
| MoS2-quantum dot triggered reactive oxygen species generation and depletion: responsible for enhanced chemiluminescence;Xiangnan Dou等;《Chem. Sci.》;20181015(第10期);第497-500页 * |
| Tumor microenvironment responsive FePt/MoS2 nanocomposites with chemotherapy and photothermal therapy for enhancing cancer immunotherapy;Dongsheng Zhang等;《Nanoscale》;20190912(第11期);第19912-19922页 * |
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