CN113398255B - Manganese dioxide/iron platinum composite nano material with synergistic catalysis function and preparation method and application thereof - Google Patents
Manganese dioxide/iron platinum composite nano material with synergistic catalysis function and preparation method and application thereof Download PDFInfo
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- C12Y101/03004—Glucose oxidase (1.1.3.4)
Abstract
The invention provides a manganese dioxide/iron platinum composite nano material with a concerted catalysis function, a preparation method and application thereof, and belongs to the technical field of antitumor drugs. The preparation method comprises the following steps of ultrasonically mixing FePt nanoparticles, unsaturated fatty acid and a polar organic solvent to obtain a mixed solution of the FePt nanoparticles and the unsaturated fatty acid; the invention mixes the pre-dispersion liquid with potassium permanganate solution to carry out reduction reaction, the unsaturated fatty acid in the pre-dispersion liquid reduces the potassium permanganate into manganese dioxide, because the surface of FePt nano particles is attached with the unsaturated fatty acid, the carboxyl can be combined with the manganese dioxide, the manganese dioxide grows on the surface of the FePt nano particles, and MnO is obtained2@ FePt nanomaterial. In the invention, MnO is added2The @ FePt nano material is stirred and mixed with glucose oxidase, bovine serum albumin and water, and the glucose oxidase and the bovine serum albumin can be loaded on the surface of manganese dioxide.
Description
Technical Field
The invention relates to the technical field of antitumor drugs, and particularly relates to a manganese dioxide/iron platinum composite nano material with a synergistic catalytic function, and a preparation method and application thereof.
Background
Tumors have become one of the major diseases threatening human health, and the morbidity and mortality of the tumors are continuously rising. At present, conventional treatment means of tumors comprise surgical resection, chemotherapy, radiotherapy and the like, however, the conventional treatment methods of tumors have the defects of large side effect, high recurrence rate, low treatment efficiency and the like.
In recent years, many novel tumor treatment methods, such as chemokinetic therapy and starvation therapy, have been developed based on the catalytic reaction in vivo. Wherein the chemokinetic therapy is a method of reacting hydrogen peroxide (H) with Fenton's reaction or Fenton-like reaction of inorganic metal nanomaterial2O2) Catalyzes the generation of hydroxyl radicals (. OH) with high oxidative toxicity, leading to apoptosis. Starvation therapy is the process of cutting off the energy supply to tumor cells, causing the cells to die as a result of "starvation". Glucose (glu) is considered to be a major source of energy for tumor cells, and thus, reducing the glucose content in cells can effectively inhibit the growth of tumor cells. Glucose oxidase (GOx) is a common natural enzyme, and can catalyze glucose decomposition under a physiological environment, so that the content of GOx at a tumor tissue is increased, glucose decomposition can be remarkably catalyzed, the capacity supply of tumor cells is cut off, and hunger treatment of tumors is realized.
However, the above catalytic reactions have respective limitations in practical applications. Due to H in cells2O2The limited content results in insufficient amount of OH catalytically produced in fenton's reaction, so that the chemo-kinetic therapy is limited in tumor treatment. On the other hand, the catalytic glucose degradation reaction of GOx requires the consumption of oxygen, which has obvious contradiction with the self acidic and anoxic environments of tumor tissues, and greatly limits the application of the catalytic therapy in tumor treatment.
Disclosure of Invention
In view of this, the present invention aims to provide a manganese dioxide/iron platinum composite nanomaterial with a concerted catalysis function, and a preparation method and an application thereof. The manganese dioxide/iron platinum composite nano material has catalase activity, glucose oxidase activity and Fenton catalytic performance, and can be used for the synergistic treatment of the chemokinetic therapy and the starvation therapy of tumors.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a preparation method of a manganese dioxide/iron platinum composite nano material with a synergistic catalytic function, which comprises the following steps:
(1) ultrasonically mixing FePt nanoparticles, unsaturated fatty acid and a polar organic solvent, and removing the polar organic solvent to obtain a pre-dispersion liquid;
(2) mixing the pre-dispersion solution with a potassium permanganate solution, and carrying out reduction reaction to obtain MnO2@ FePt nanomaterial;
(3) MnO is added to the mixture2The @ FePt nano material is stirred and mixed with glucose oxidase, bovine serum albumin and water to obtain the manganese dioxide/iron platinum composite nano material with the synergistic catalysis function.
Preferably, the particle size of the FePt nanoparticles is 3-4 nm.
Preferably, the unsaturated fatty acid is one or more of oleic acid, myristoleic acid, palmitoleic acid, erucic acid, ricinoleic acid, linoleic acid, linolenic acid and arachidonic acid.
Preferably, the volume ratio of the mass of the FePt nanoparticles to the unsaturated fatty acid in the step (1) is 3-7 mg: 1-7 mL.
Preferably, the concentration of the potassium permanganate solution is 15-30 mM; the volume ratio of the mass of the FePt nano particles to the potassium permanganate solution is 3-7 mg: 20-35 mL.
Preferably, the temperature of the reduction reaction in the step (2) is 20-45 ℃ and the time is 8-12 h.
Preferably, MnO in said step (3)2The mass ratio of the @ FePt nano material to the glucose oxidase and the bovine serum albumin is (4-8): (1-3): 2-5).
The invention provides a manganese dioxide/iron platinum composite nano material with a synergistic catalytic function, which is prepared by the preparation method and comprises iron platinum nano particles, manganese dioxide growing on the surfaces of the iron platinum nano particles, and glucose oxidase and bovine serum albumin loaded on the surfaces of the manganese dioxide.
Preferably, the particle size of the manganese dioxide/iron platinum composite nano material with the concerted catalysis function is 100-200 nm.
The invention provides application of the manganese dioxide/iron platinum composite nano material with the synergistic catalytic function in preparing an anti-tumor medicament.
The invention provides a preparation method of a manganese dioxide/iron platinum composite nano material with a synergistic catalytic function, which comprises the following steps: (1) ultrasonically mixing FePt nanoparticles, unsaturated fatty acid and a polar organic solvent, and removing the polar organic solvent to obtain a pre-dispersion liquid; (2) mixing the pre-dispersion solution with a potassium permanganate solution, and carrying out reduction reaction to obtain MnO2@ FePt nanomaterial; (3) MnO is added to the mixture2The @ FePt nano material is stirred and mixed with glucose oxidase, Bovine Serum Albumin (BSA) and water to obtain the manganese dioxide/iron platinum composite nano material with the synergistic catalysis function. The method comprises the steps of ultrasonically mixing FePt nanoparticles, unsaturated fatty acid and a polar organic solvent to obtain a mixed solution of the FePt nanoparticles and the unsaturated fatty acid; the invention mixes the pre-dispersion liquid with potassium permanganate solution to carry out reduction reaction, the unsaturated fatty acid in the pre-dispersion liquid reduces the potassium permanganate into manganese dioxide, because the surface of FePt nano particles is attached with the unsaturated fatty acid, the carboxyl can be combined with the manganese dioxide, the manganese dioxide grows on the surface of the FePt nano particles, and MnO is obtained2@ FePt nanomaterial. In the invention, MnO is added2The @ FePt nano material is stirred and mixed with glucose oxidase, bovine serum albumin and water, and the glucose oxidase and the bovine serum albumin can be loaded on the surface of manganese dioxide.
In the present invention, on the one hand, glucose oxidase (GOx) is able to catalyze the decomposition of glucose in cells, so that the cells are not supplied with energyDeath due to foot, MnO2Has better catalase activity, and can catalyze H in the acidic environment of tumor tissues2O2Decomposition to O2The catalytic performance of GOx can be greatly promoted by increasing the oxygen content, so that the hunger treatment effect is improved; on the other hand, GOx catalyzes gluconic acid and H produced in the glucose decomposition process2O2Can be matched with MnO2Further reaction, thereby increasing O2The supply of (2). Thus, MnO2Can form a circulating reaction with GOx, thereby enhancing the catalytic effect of GOx and improving the hunger treatment effect.
Meanwhile, FePt is decomposed to generate Fe in the acidic environment of tumor tissues2+It is an effective Fenton reaction catalyst, and can catalyze H in cells2O2Decomposition produces OH with high oxidative toxicity, thereby causing apoptosis. H produced during glucose decomposition2O2Can effectively increase H in cells2O2Thereby greatly increasing the content of OH, and consequently enhancing the therapeutic effect of the chemo-kinetic therapy. Therefore, the manganese dioxide/iron platinum composite nano material has catalase activity, glucose oxidase activity and Fenton catalytic performance, and can be used for the synergistic treatment of the chemokinetic therapy and the starvation therapy of tumors.
Drawings
FIG. 1 is a TEM image of BGMFP;
FIG. 2 shows H under different conditions2O2A graph of content variation of (a);
FIG. 3 shows O under different conditions2A graph of content variation of (a);
FIG. 4 is a fluorescence emission spectrum of a solution under different conditions;
FIG. 5 shows the survival rate of 4T1 cells after culturing different materials;
FIG. 6 is a graph showing the relative tumor volume changes in mice cultured with different injected materials.
Detailed Description
The invention provides a preparation method of a manganese dioxide/iron platinum composite nano material with a synergistic catalytic function, which comprises the following steps:
(1) ultrasonically mixing FePt nanoparticles, unsaturated fatty acid and a polar organic solvent, and removing the polar organic solvent to obtain a pre-dispersion liquid;
(2) mixing the pre-dispersion solution with a potassium permanganate solution, and carrying out reduction reaction to obtain MnO2@ FePt nanomaterial;
(3) MnO is added to the mixture2The @ FePt nano material is stirred and mixed with glucose oxidase, bovine serum albumin and water to obtain the manganese dioxide/iron platinum composite nano material with the concerted catalysis function.
The method comprises the steps of ultrasonically mixing FePt nanoparticles, unsaturated fatty acid and a polar organic solvent, and removing the polar organic solvent to obtain a pre-dispersion liquid. In the invention, the particle size of the FePt nanoparticles is preferably 3-4 nm; the molar ratio of Fe to Pt in the FePt nanoparticles is preferably 1: 1. The invention has no special requirement on the source of the FePt nano particles, and the FePt nano particles which are commercially available in the field can be used or prepared by self. When the FePt nanoparticles are prepared by self, the preparation method refers to a document Bioconjugate chem.2017,28,400-409, platinum acetylacetonate and iron acetylacetonate are respectively used as a platinum source and an iron source, 1, 2-hexadecane diol is used as a reducing agent, and dioctyl ether, oleylamine and oleic acid are used as solvents, and the FePt nanoparticles are prepared by a high-temperature thermal reduction mode.
In the present invention, the unsaturated fatty acid is preferably one or more of oleic acid, myristoleic acid, palmitoleic acid, erucic acid, ricinoleic acid, linoleic acid, linolenic acid, and arachidonic acid, and is more preferably oleic acid. In the invention, the volume ratio of the mass of the FePt nanoparticles to the unsaturated fatty acid is preferably 3-7 mg: 1-7 mL, more preferably 4-6 mg: 1-5 mL.
In the present invention, the polar organic solvent is preferably one or more of chloroform, dichloromethane, methanol and acetonitrile. In the invention, the volume ratio of the mass of the FePt nanoparticles to the polar organic solvent is preferably 3-7 mg: 10-20 mL, more preferably 4-6 mg: 15 mL.
In the invention, the power of the ultrasonic mixing is preferably 120W, and the time is preferably 20-30 min, and more preferably 25 min. According to the invention, preferably, the FePt nanoparticles and the polar organic solvent are ultrasonically mixed for 10-20 min, and then the unsaturated fatty acid is added and ultrasonically mixed for 20-30 min.
The present invention has no special requirement on the way of removing the polar organic solvent, and the way of removing the polar organic solvent, which is well known to those skilled in the art, can be used, such as rotary evaporation.
After the pre-dispersion liquid is obtained, the pre-dispersion liquid is mixed with a potassium permanganate solution for reduction reaction to obtain MnO2@ FePt nanomaterial. In the invention, the molar concentration of the potassium permanganate solution is preferably 15-30 mM, and more preferably 20-25 mM. In the invention, the volume ratio of the mass of the FePt nanoparticles to the potassium permanganate solution is preferably 3-7 mg: 20-35 mL, more preferably 4-6 mg: 25-30 mL.
The invention does not require any particular mixing means, such as stirring, known to the person skilled in the art. In the invention, the temperature of the reduction reaction is preferably 25 ℃, and the time is preferably 8-12 h, and more preferably 10 h.
After the reduction reaction is completed, the present invention preferably performs post-treatment on the obtained reduction reaction solution, and the post-treatment preferably includes the following steps:
the obtained reduction reaction solution was centrifuged and washed, and the obtained solid was dispersed in water for storage.
The present invention does not require any particular means for centrifugation, and centrifugation means well known to those skilled in the art may be used. In the present invention, the washing is performed on the centrifuged solid, the washing detergent is preferably absolute ethanol, and the number of washing is preferably three.
Obtaining said MnO2After @ FePt nano material, the invention uses MnO2The @ FePt nano material is stirred and mixed with glucose oxidase, bovine serum albumin and water to obtain the manganese dioxide/iron platinum composite nano material with the synergistic catalysis function. In the present invention, the glucose oxidase is preferably derived from kojiMildew; the source of the glucose oxidase is not particularly required, and the glucose oxidase which is commercially available and is conventional in the field is used. As a specific example of the present invention, the glucose oxidase is purchased from Chiloeei (Shanghai) chemical industry development Co., Ltd.
The source of the bovine serum albumin has no special requirement, and the bovine serum albumin which is conventional and commercially available in the field can be used. In the invention, the bovine serum albumin can increase the stability of the composite nano material in water.
In the present invention, the MnO2The mass ratio of the @ FePt nano material to the glucose oxidase and the bovine serum albumin is preferably (4-8): 1-3): 2-5, and more preferably 5:1.5: 3. In the present invention, the stirring and mixing method is preferably:
(a) MnO of2Dispersing the @ FePt nano material in water, adding glucose oxidase, and sequentially carrying out first stirring and mixing to obtain GOx @ MnO2@ FePt nanomaterial;
(b) mixing GOx @ MnO2And dispersing the @ FePt nano material in water, adding bovine serum albumin, and sequentially carrying out second stirring and mixing to obtain the manganese dioxide/iron platinum composite nano material with the synergistic catalysis function, which is marked as the BGMFP nano composite material.
In the present invention, the temperature of the first stirring and mixing is preferably room temperature, and the time is preferably 10 hours. After the first stirring and mixing, the present invention preferably performs centrifugation and washing on the obtained mixed solution. The present invention does not require any particular means for centrifugation, and centrifugation means well known to those skilled in the art may be used. In the present invention, the detergent for washing is preferably deionized water, and the number of washing is preferably 3.
In the invention, the temperature of the second stirring and mixing is preferably room temperature, and the time is preferably 5-9 h, and more preferably 6-8 h. After the second stirring and mixing, the present invention preferably performs centrifugation and washing on the obtained mixed solution. The present invention does not require any particular means for centrifugation, and centrifugation means well known to those skilled in the art may be used. In the present invention, the washing detergent is preferably deionized water, and the number of washing is preferably 3.
After the manganese dioxide/iron platinum composite nano material with the concerted catalysis function is obtained, the composite dense material is preferably dispersed in water and is refrigerated at 4 ℃ for later use.
The invention provides a manganese dioxide/iron platinum composite nano material with a concerted catalysis function, which is prepared by the preparation method, and comprises iron platinum nano particles, manganese dioxide growing on the surfaces of the iron platinum nano particles, and glucose oxidase and bovine serum albumin loaded on the surfaces of the manganese dioxide.
In the invention, the particle size of the manganese dioxide/iron platinum composite nano material with the synergistic catalytic function is preferably 100-200 nm, and more preferably 130-150 nm.
The invention provides application of the manganese dioxide/iron platinum composite nano material with the synergistic catalytic function in preparing an anti-tumor medicament. In the invention, the manganese dioxide/iron platinum composite nano material with the synergistic catalytic function can be used for the synergistic treatment of the chemodynamic therapy and the hunger therapy of tumors.
The manganese dioxide/iron platinum composite nanomaterial with a concerted catalytic function provided by the invention and the preparation method and application thereof are described in detail below with reference to the examples, but the manganese dioxide/iron platinum composite nanomaterial with a concerted catalytic function and the preparation method and application thereof are not to be construed as limiting the scope of the invention.
Example 1
(1) Preparation of FePt nanoparticles
0.39g of platinum acetylacetonate and 0.35g of iron acetylacetonate were added to a mixed solution of 43mL of dioctyl ether and 0.78g of 1, 2-hexadecanediol, the mixture was heated to 110 ℃ for 15 minutes under the protection of argon, 0.22mL of oleylamine and 0.21mL of oleic acid were added, and the mixture was heated to 295 ℃ for 1 hour. Centrifuging after the reaction is finished, and washing with ethanol to obtain FePt nanoparticles with the particle size of 3 nm.
(2)MnO2Preparation of @ FePt:
5mg of FePt nanoparticles with the particle size of 3nm are dispersed in 12mL of chloroform, and 1.5mL of oleic acid is added after ultrasonic treatment for 5 min. Continuing the sonication for 25min, and then mixing the mixtureAnd (4) removing the trichloromethane by rotary evaporation. Finally, the solid-liquid mixture after rotary evaporation is added into 30mL of 20mM potassium permanganate solution and stirred overnight at 25 ℃. After the reaction is finished, centrifugal separation is carried out, and the solid is washed for 3 times by absolute ethyl alcohol to obtain MnO2@ FePt nanomaterial, and finally dispersing the material in water.
(3) Preparation of BGMFP:
adding 5mg of MnO2@ FePt was dispersed in distilled water, and 1.5mg of GOx was then added thereto, stirred at room temperature for 10 hours, and then centrifuged, and the solid was washed with distilled water 3 times to obtain GOx @ MnO2@ FePt nano material, dispersing the material in distilled water for later use. To GOx @ MnO2@ FePt material solution was added with 3mgBSA, stirred at room temperature for 6 hours, and then centrifuged. Washing the solid with distilled water for 3 times to obtain the BGMFP nanocomposite, dispersing the material in distilled water, and refrigerating at 4 ℃ for later use.
Comparative examples 1 to 3
(1) The FePt nano particles are omitted from adding, the oleic acid and the potassium permanganate solution are directly mixed, the BSA is added and stirred, and the BSA @ MnO is obtained2The material used in comparative example 1 was the same as in example 1.
(2) The FePt nano particles are omitted from adding, the oleic acid and the potassium permanganate solution are directly mixed, and then the GOx and the BSA are sequentially added and stirred to obtain the BSA-GOx @ MnO2As comparative example 2, the same amount of the raw materials as in example 1 was used.
(3) Omitting the addition of GOx, as compared with example 1, to obtain BSA @ MnO2@ FePt as comparative example 3.
Structural characterization and Performance testing
Structural characterization of BGMFPs
The transmission electron micrograph of the BGMFP nanocomposite obtained in example 1 is shown in fig. 1. As can be seen from fig. 1, the prepared BGMFP nanocomposite has a flower shape, a particle size of about 130nm, and punctate FePt nanoparticles can be seen on manganese dioxide, which has good dispersibility in water.
Potential of (II) BGMFP
Measurement of BSA-GOx@MnO2The potential of @ FePt is-15.5 mV, which indicates that the material has better stability.
Catalytic Performance of (III) BGMFP
(1) To contain H2O2(250. mu. mol/L) to this solution were added BGMFP (100. mu.g/mL) and glucose (Glu) (250. mu.g/mL) as test groups, which were designated BGMFP + H2O2+ Glu, test at different times H2O2The results obtained with the variation of the contents are shown in FIG. 2.
Meanwhile, different control groups are set, and compared with the test group, the control group 1 is not added with glucose and is marked as BGMFP + H2O2(ii) a Compared with the test group, the control group 2 has the BGMFP replaced by equal concentration of GOx, and the concentration is recorded as GOx + H2O2+ Glu; control group 3 was 250. mu. mol/L H2O2And (3) solution.
As can be seen from FIG. 2, the catalyst contains H2O2(250. mu. mol/L) solution was added BGMFP (100. mu.g/mL) and glucose (250. mu.g/mL) to obtain H in solution2O2The content gradually decreases mainly due to H2O2MnO in the material2Catalytic decomposition such that the concentration thereof is reduced; with MnO in the material2Consumed, H in solution after 6 minutes2O2The content gradually increased and reached about 600. mu. mol/L at 30 minutes, indicating that GOx in the composite material can effectively catalyze the decomposition of glucose, so that H2O2The content gradually increases. In the control group, H in the solution with only BGMFP added2O2The content is always reduced; adding GOx and glucose solution H2O2The content is always increased, and H2O2The content is higher than that of the experimental group, which shows that GOx can decompose glucose to ensure that H in the solution2O2The content increases. The results show that BGMFP can effectively catalyze the decomposition of glucose, thereby increasing H in solution2O2The content of (a).
(2) To contain H2O2(250. mu. mol/L) to this solution were added BGMFP (100. mu.g/mL) and glucose (Glu) (250. mu.g/mL) as test groups, which were designated BGMFP + H2O2+ Glu, not tested simultaneouslyThe change in the oxygen content of the solution over time gave the results shown in FIG. 3.
Meanwhile, different control groups were set, and control group 1 was compared with the test group without adding H2O2Denoted as BGMFP + Glu; control group 2 BGMFP, H were compared to test group2O2Replacing the substitution into GOx, and marking as GOx + Glu; control group 3 was 250. mu. mol/L H2O2A solution; the control group 4 is BGMFP of 100. mu.g/mL; control 5 was water.
As can be seen from FIG. 3, when H is contained in the mixture2O2(250. mu. mol/L) solution, after adding BGMFP (100. mu.g/mL) and glucose (250. mu.g/mL), O in the solution2The content gradually increased to indicate MnO in the composite material2Capable of catalyzing H2O2Decomposition into O2So that O in the solution2The content increased, indicating that BGMFP had better oxygen supply performance. But as the reaction proceeded (about 30 minutes), O in solution2The content is gradually reduced mainly because the GOx in the composite material consumes O in the process of decomposing glucose2So that O is2The content decreases, and as the reaction reaches equilibrium, O in solution2The content remains unchanged and higher than the O content in the initial solution2And (4) content. In control group, BGMFP, H2O2And H2O in O solution2The content is kept constant, and the solution added with BGMFP-glucose and GOx-glucose leads to O due to glucose decomposition2The content gradually decreases. The results show that BGMFP has better synergistic catalytic function.
(3) To contain H2O2(250. mu. mol/L) to this solution were added BGMFP (100. mu.g/mL) and glucose (Glu) (250. mu.g/mL) as test groups, which were designated BGMFP + H2O2+ Glu, the change in. OH content in the test solution, the results obtained are shown in FIG. 4. As can be seen from FIG. 4, the control group (PBS solution, H)2O2Solution and MnO2-H2O2Solution) BGMFP-H2O2The solution emits stronger fluorescence signals, which indicates that BGMFP can effectively catalyze H2O2Decomposition to produce OH to BGMFP-H2O2After glucose is added into the solution, the fluorescence intensity of the BGMFP is obviously enhanced, which shows that the BGMFP can effectively catalyze the decomposition of glucose and increase H in the solution2O2The content of (2) further increases the amount of OH produced. This result further indicates that BGMFP has a better synergistic catalytic function.
(IV) cell viability assay for BGMFP
In order to examine the tumor inhibition performance of the composite material BGMFP, the influence of different concentrations of BGMPF on the survival rate of 4T1 cells was examined by the following method:
culturing the cells in a 96-well plate, wherein the cell content in each well is 106At one time, the material was added and the culture was carried out for 12 hours. The cells were then washed 3 times and the viability of the cells was determined using the WST-1 assay kit. The WST-1 kit was purchased from Biyuntian Bioreagent.
The results are shown in FIG. 5. As can be seen from fig. 5, the survival rate of 4T1 cells gradually decreased after the cells were cultured with different amounts of BGMFP. With control group (cells respectively treated with FePt, GOx, BSA @ MnO at different contents)2，BSA-GOx@MnO2And BSA @ MnO2@ FePt culture) compared with the results, the survival rate of 4T1 cells after BGMFP culture was much lower than that of the control group, indicating that BGMFP has a better inhibitory effect on tumor cells.
(V) experiment of BGMFP inhibition of mouse tumors
Experimental BGMFP and control PBS, BSA @ MnO2，BSA-GOx@MnO2And BSA @ MnO2@ FePt) were injected into mice via the tail vein, respectively (material concentrations were all 1mg/mL, injection volume was 100. mu.L. The number of mice in the experimental group and the control group was 5), and the sizes of the tumors of the mice were recorded, and the relative volumes (the ratio of the tumor volume after the treatment of the mice to the volume before the treatment) were calculated, and the results are shown in fig. 6. As can be seen in FIG. 6, PBS and BSA @ MnO were injected2The relative volume of the tumor of the mice is continuously increased, and BSA-GOx @ MnO is injected2And BSA @ MnO2The results show that the relative tumor volume of the mice is inhibited to a certain extent after @ FePt, but the tumor volume is still obviously increased, while the tumor size of the mice with BGMFP is not greatly changed, and the results show that the BGMF has the advantages of high tumor volume, high tumor volume and low tumor sizeP has the best inhibition effect on mouse tumors, and can be used for the synergistic treatment of the chemo-kinetic therapy and the hunger therapy of the tumors.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (8)
1. A preparation method of manganese dioxide/iron platinum composite nano material with a synergistic catalytic function comprises the following steps:
(1) ultrasonically mixing FePt nanoparticles, unsaturated fatty acid and a polar organic solvent, and removing the polar organic solvent to obtain a pre-dispersion liquid; the particle size of the FePt nano particles is 3-4 nm; the unsaturated fatty acid is oleic acid;
(2) mixing the pre-dispersion solution with a potassium permanganate solution, and carrying out reduction reaction to obtain MnO2@ FePt nanomaterial;
(3) MnO is added to the mixture2The @ FePt nano material is stirred and mixed with glucose oxidase, bovine serum albumin and water to obtain the manganese dioxide/iron platinum composite nano material with the concerted catalysis function.
2. The preparation method according to claim 1, wherein the volume ratio of the mass of the FePt nanoparticles to the unsaturated fatty acid in the step (1) is 3-7 mg: 1-7 mL.
3. The preparation method according to claim 1, wherein the concentration of the potassium permanganate solution is 15 to 30 mM; the volume ratio of the mass of the FePt nano particles to the potassium permanganate solution is 3-7 mg: 20-35 mL.
4. The preparation method according to claim 1, wherein the temperature of the reduction reaction in the step (2) is 20-45 ℃ and the time is 8-12 h.
5. The method according to claim 1, wherein MnO in the step (3)2The mass ratio of the @ FePt nano material to the glucose oxidase and the bovine serum albumin is (4-8): (1-3): 2-5).
6. The manganese dioxide/iron platinum composite nanomaterial with the synergistic catalytic function, which is prepared by the preparation method of any one of claims 1 to 5, comprises iron platinum nanoparticles, manganese dioxide growing on the surfaces of the iron platinum nanoparticles, and glucose oxidase and bovine serum albumin loaded on the surfaces of the manganese dioxide.
7. The manganese dioxide/iron platinum composite nanomaterial with a concerted catalytic function of claim 6, wherein the particle size of the manganese dioxide/iron platinum composite nanomaterial with a concerted catalytic function is 100-200 nm.
8. The use of the manganese dioxide/iron platinum composite nanomaterial with a concerted catalytic function as defined in claim 6 or 7 in the preparation of an anti-tumor medicament.
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| CN111450270A (en) * | 2020-04-24 | 2020-07-28 | 西南大学 | Construction and application of catalytic nanoparticles based on glucose oxidase/iron phosphate |
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| CN111450270A (en) * | 2020-04-24 | 2020-07-28 | 西南大学 | Construction and application of catalytic nanoparticles based on glucose oxidase/iron phosphate |
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|---|
| 功能纳米复合材料的制备及抗肿瘤活性研究;杨包产等;《中国化学会第八届全国物理无机化学学术会议论文集（一）》;20180430;第86页 * |
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