CN115192604B - Preparation method of ruthenium nanomaterial, and product and application thereof - Google Patents
Preparation method of ruthenium nanomaterial, and product and application thereof Download PDFInfo
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- CN115192604B CN115192604B CN202210570142.6A CN202210570142A CN115192604B CN 115192604 B CN115192604 B CN 115192604B CN 202210570142 A CN202210570142 A CN 202210570142A CN 115192604 B CN115192604 B CN 115192604B
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- 239000002086 nanomaterial Substances 0.000 title claims abstract description 89
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 title claims abstract description 79
- 229910052707 ruthenium Inorganic materials 0.000 title claims abstract description 79
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 230000036542 oxidative stress Effects 0.000 claims abstract description 23
- 201000010099 disease Diseases 0.000 claims abstract description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 20
- QGLWBTPVKHMVHM-KTKRTIGZSA-N (z)-octadec-9-en-1-amine Chemical compound CCCCCCCC\C=C/CCCCCCCCN QGLWBTPVKHMVHM-KTKRTIGZSA-N 0.000 claims abstract description 11
- 229910021642 ultra pure water Inorganic materials 0.000 claims abstract description 10
- 239000012498 ultrapure water Substances 0.000 claims abstract description 10
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 9
- 238000001027 hydrothermal synthesis Methods 0.000 claims abstract description 8
- YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 239000003814 drug Substances 0.000 claims abstract description 4
- 238000002156 mixing Methods 0.000 claims abstract description 3
- 230000001376 precipitating effect Effects 0.000 claims abstract description 3
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- 206010067125 Liver injury Diseases 0.000 claims description 16
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- 239000002202 Polyethylene glycol Substances 0.000 claims description 9
- 229920001223 polyethylene glycol Polymers 0.000 claims description 9
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 9
- 150000003303 ruthenium Chemical class 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 3
- 238000012986 modification Methods 0.000 claims 1
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- 230000000694 effects Effects 0.000 abstract description 25
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 11
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- 229910052760 oxygen Inorganic materials 0.000 abstract description 11
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- 230000002292 Radical scavenging effect Effects 0.000 abstract description 6
- 230000002789 catalaselike Effects 0.000 abstract description 6
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 abstract description 6
- 238000000338 in vitro Methods 0.000 abstract description 3
- 238000001727 in vivo Methods 0.000 abstract description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 14
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 8
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
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- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
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- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 238000004445 quantitative analysis Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 102000019197 Superoxide Dismutase Human genes 0.000 description 3
- 108010012715 Superoxide dismutase Proteins 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 231100000234 hepatic damage Toxicity 0.000 description 3
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- 239000002609 medium Substances 0.000 description 3
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- BIXNGBXQRRXPLM-UHFFFAOYSA-K ruthenium(3+);trichloride;hydrate Chemical compound O.Cl[Ru](Cl)Cl BIXNGBXQRRXPLM-UHFFFAOYSA-K 0.000 description 3
- -1 superoxide anions Chemical class 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
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- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 1
- 108010082126 Alanine transaminase Proteins 0.000 description 1
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 1
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 1
- 229940124602 FDA-approved drug Drugs 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- URNSECGXFRDEDC-UHFFFAOYSA-N N-acetyl-1,4-benzoquinone imine Chemical compound CC(=O)N=C1C=CC(=O)C=C1 URNSECGXFRDEDC-UHFFFAOYSA-N 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
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- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
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- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
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- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- B22F1/00—Metallic powder; Treatment of metallic powder, e.g. to facilitate working or to improve properties
- B22F1/05—Metallic powder characterised by the size or surface area of the particles
- B22F1/054—Nanosized particles
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Abstract
The invention discloses a preparation method of a ruthenium nano material, which comprises the following steps: dissolving ruthenium chloride in ultrapure water, dissolving oleylamine in cyclohexane, mixing the two, performing hydrothermal reaction, and precipitating by a poor solvent after the reaction is finished to obtain the ruthenium nanomaterial. The invention also discloses the ruthenium nano material obtained by the preparation method and application thereof in preparing medicaments for treating oxidative stress related diseases. The ruthenium nano material prepared by the invention has good catalase-like activity, superoxide dismutase-like activity and hydroxyl radical scavenging capability, and can efficiently scavenge active oxygen in vivo and in vitro, thereby realizing the treatment of diseases related to oxidative stress.
Description
Technical Field
The invention relates to preparation and application of a nano biological material, in particular to a preparation method of a ruthenium nano material, a product and application thereof.
Background
Oxidative stress is one of the important factors causing many diseases, such as brain injury, liver injury, kidney injury, skin injury, parkinson's disease, ischemic stroke, myocardial infarction, and the like. Oxidative stress can lead to injury and oxidation of endogenous biological macromolecules (e.g., proteins, lipids, and nucleic acids, etc.), causing impaired function. Therefore, modulation of oxidative stress microenvironment is an effective strategy for treating oxidative stress related diseases. The natural antioxidant enzyme can effectively remove active oxygen, relieve oxidative stress, and is an ideal antioxidant. However, natural enzymes are limited in clinical applications due to their inherent disadvantages such as poor stability, high cost, large environmental impact on catalytic activity, etc. Nano enzyme is a kind of nano material with enzyme-like activity, and is widely studied for disease treatment due to the advantages of high stability, mass production, easy preservation, adjustable catalytic activity and the like. Among them, nanoezymes having active oxygen scavenging ability are receiving increasing attention in diseases related to oxidative stress. For example, the nano enzyme with catalase and superoxide dismutase can catalyze and decompose active oxygen such as hydrogen peroxide, superoxide anions and the like into water and oxygen, so that oxidative stress is effectively relieved, and a disease treatment effect is realized.
In recent years, nano-enzymes based on noble metal nano-materials have been widely used in biosensing, drug delivery, disease diagnosis, disease treatment, and the like, due to their good catalytic activity. Wherein, the ruthenium nano material has various enzyme activities including catalase, superoxide dismutase and peroxidase; and compared with other noble metals, ruthenium has low cost and high stability. Thus, nanoezymes based on ruthenium nanomaterials are gaining increasing attention in oxidative stress related diseases. In addition, ruthenium-based complexes have entered clinical trials as anticancer drugs. Although ruthenium nanomaterials show a broad prospect in diseases related to oxidative stress, their relatively low enzyme-like catalytic performance and ambiguous catalytic mechanism prevent their practical application as therapeutic agents. Therefore, regulating the enzyme-like activity of ruthenium nanomaterial is critical for further broad application of ruthenium-based nanoenzyme.
Recent studies have shown that decreasing the size of noble metal nanomaterials can increase the proportion of their low-coordination surface atoms, thereby increasing the adsorption energy of oxygen on the nanomaterials, resulting in an increase in the oxidation state of the nanomaterials surface. Considering that the oxidation state is critical to the antioxidant enzyme-like activity of the metal nanomaterial, we speculate that size effect mediated regulation of the oxidation state can directly regulate the antioxidant activity of the ruthenium nanomaterial.
Acetaminophen-induced liver injury is a typical oxidative stress-related disease. Excess acetaminophen is metabolized to N-acetyl-p-benzoquinone imine in the liver and further depletes glutathione in the liver tissue, resulting in accumulation of reactive oxygen species in the liver tissue, causing hepatocyte necrosis, resulting in liver damage. N-acetylcysteine is the only FDA approved drug for treating acetaminophen-induced liver injury, and can promote the biosynthesis of glutathione, thereby relieving the oxidative stress of the liver injury site. However, N-acetylcysteine has a significant therapeutic effect on acetaminophen-induced liver injury only in the early stages of injury occurrence, and its therapeutic effect is significantly reduced in the later stages of injury. Thus, there is a great need to develop antioxidants with a longer treatment time window for the treatment of acetaminophen-induced liver damage.
Disclosure of Invention
The invention aims to provide a preparation method of a ruthenium nano material, a product and application thereof, and the obtained ruthenium nano material has good catalase-like activity, superoxide dismutase-like activity and hydroxyl radical scavenging capacity, and can efficiently scavenge active oxygen in vivo and in vitro, thereby realizing the treatment of diseases related to oxidative stress.
The invention provides the following technical scheme:
a method of preparing a ruthenium nanomaterial, the method comprising: dissolving ruthenium chloride in ultrapure water, dissolving oleylamine in cyclohexane, mixing the two, performing hydrothermal reaction, and precipitating by a poor solvent after the reaction is finished to obtain the ruthenium nanomaterial.
According to the invention, the aqueous solution of ruthenium chloride and the cyclohexane solution of oleylamine are firstly mixed into uniform emulsion, and then the ruthenium chloride is reduced by the oleylamine in the hydrothermal reaction process, so that the ruthenium nanomaterial is obtained. The grain diameter of the ruthenium nano material prepared by the invention is 1-20nm.
The feed ratio of ruthenium chloride, oleylamine, ultrapure water and cyclohexane is 5-200 mg:0.02-2 g:1-100 ml:0.5-50 ml.
The temperature of the hydrothermal reaction is 100-260 ℃ and the reaction time is 0.5-72 h.
The size of the ruthenium nanomaterial can be regulated and controlled by regulating the feed ratio of ruthenium chloride, oleylamine, ultrapure water and cyclohexane, the temperature of the hydrothermal reaction and the time of the hydrothermal reaction.
The ruthenium nanomaterial is finally obtained by precipitation of a poor solvent. The poor solvent is one or more selected from ethanol, acetone, methanol, ethyl acetate, acetonitrile, dimethyl imine and dimethyl sulfoxide.
The preparation method of the ruthenium nano material also comprises the following steps: and modifying the ruthenium nanomaterial by sulfhydryl polyethylene glycol to convert the ruthenium nanomaterial from lipophilicity to hydrophilicity to obtain the ruthenium nanomaterial dispersed in water. The mass feeding ratio of the ruthenium nano material to the sulfhydryl polyethylene glycol is 1:1-50.
The hydraulic diameter of the sulfhydryl polyethylene glycol modified ruthenium nano material is 2-40 nm.
The invention also provides the ruthenium nano material obtained by the preparation method.
The invention also provides application of the ruthenium nanomaterial in preparing a medicament for treating oxidative stress related diseases.
The oxidative stress-related diseases described in the present invention are diseases caused by oxidative damage of tissues caused by oxidative stress of the body, including brain damage, liver damage, kidney damage, skin damage, parkinson's disease, ischemic stroke, myocardial infarction, etc.
The ruthenium nano material provided by the invention has catalase-like activity, superoxide dismutase-like activity and hydroxyl radical scavenging capability, and can scavenge active oxygen in damaged tissues, relieve oxidative stress and realize the effect of disease treatment.
Specifically, the ruthenium nano material can be enriched in damaged liver tissues, and plays roles of catalase activity, superoxide dismutase-like activity and hydroxyl radical scavenging capacity, so that biological macromolecules such as lipid, nucleic acid, protein and the like are prevented from being damaged by oxidative stress, and liver necrosis areas are reduced, and the treatment of acetaminophen-induced liver injury is realized.
Meanwhile, the ruthenium nano material can stably and efficiently exert enzyme-like activity, so that the ruthenium nano material can exert an antioxidant effect in liver tissues for a long time, has a longer treatment time window, and can be used for treating late acetaminophen-induced liver injury.
The invention provides a preparation method of the ruthenium nano material, and confirms the antioxidation of the ruthenium nano material through two aspects of in vitro cell experiments and animal experiments, thereby providing a nano material with potential for clinically treating diseases related to oxidative stress.
Compared with the prior art, the invention has the beneficial effects that:
(1) The reaction system for preparing the ruthenium nano material is mild, the cost is low, and the good conversion possibility is realized.
(2) The size of the ruthenium nano material obtained in the invention can be controlled simply by adjusting the feeding ratio of reactants, the reaction temperature and the reaction time.
(3) The ruthenium nano material obtained by the invention has good catalase-like activity, superoxide dismutase-like activity and hydroxyl radical scavenging capacity, and can scavenge active oxygen and relieve oxidative stress.
(4) The ruthenium nano material obtained by the invention can continuously exert antioxidant activity in liver tissues, and can realize the treatment of late acetaminophen-induced liver injury.
Drawings
FIG. 1 is a transmission electron micrograph of the ruthenium nanomaterial prepared in example 1;
FIG. 2 is a photograph and dynamic light scattering particle size distribution diagram of thiol-polyethylene glycol-modified ruthenium nanomaterial prepared in example 2;
FIG. 3 is a characterization of the properties of the ruthenium nanomaterial-based catalase prepared in example 2;
FIG. 4 is a characterization of the performance of the ruthenium nanomaterial-based superoxide dismutase prepared in example 2;
FIG. 5 is a characterization of the hydroxyl radical scavenging properties of the ruthenium nanomaterial prepared in example 2;
FIG. 6 is a graph showing the results of quantitative analysis of the cellular activity of the ruthenium nanomaterial prepared in example 2 on normal hepatocytes;
FIG. 7 is a graph showing the results of quantitative analysis of cell activity of the ruthenium nanomaterial prepared in example 2 to inhibit hydrogen peroxide-induced cell death;
FIG. 8 is an evaluation of the effect of the ruthenium nanomaterial prepared in example 2 on treating acetaminophen-induced liver injury.
Detailed Description
The invention will be further described with reference to specific examples and figures of the specification.
Example 1
(1) Synthesis of 2.0nm ruthenium nanomaterial (sRuNP): 40mg of ruthenium chloride hydrate is dissolved in 13ml of ultrapure water, 0.2g of oleylamine is dissolved in 2ml of cyclohexane, the two are mixed uniformly under water bath ultrasonic, the mixture is transferred into a hydrothermal kettle after being continuously stirred for 1h, the mixture is heated to 160 ℃ for reaction for 12h, the hydrothermal kettle is taken out and cooled to room temperature, ethanol is centrifuged to collect precipitate, and the ruthenium nanomaterial with the particle size of-2 nm is obtained.
(2) Synthesis of 3.9nm ruthenium nanomaterial (mRuNP): 40mg of ruthenium chloride hydrate is dissolved in 13ml of ultrapure water, 0.4g of oleylamine is dissolved in 2ml of cyclohexane, the two are mixed uniformly under water bath ultrasonic, the mixture is transferred into a hydrothermal kettle after being continuously stirred for 1h, the mixture is heated to 160 ℃ for reaction for 12h, the hydrothermal kettle is taken out and cooled to room temperature, ethanol is centrifuged to collect precipitate, and the 4nm ruthenium nanomaterial is obtained.
(3) Synthesis of 6.5nm ruthenium nanomaterial (lRuNP): 40mg of ruthenium chloride hydrate is dissolved in 13ml of ultrapure water, 0.8g of oleylamine is dissolved in 2ml of cyclohexane, the two are mixed uniformly under water bath ultrasonic, the mixture is transferred into a hydrothermal kettle after being continuously stirred for 1h, the mixture is heated to 160 ℃ for reaction for 12h, the hydrothermal kettle is taken out and cooled to room temperature, ethanol is centrifuged to collect precipitate, and the-6 nm ruthenium nanomaterial is obtained.
The three ruthenium nano materials are subjected to morphology characterization by a transmission electron microscope, and the result is shown in figure 1, wherein the particle size of sRuNP is 2.0nm, the particle size of mRuNP is 3.9nm, and the particle size of lRuNP is 6.5nm.
Example 2
Synthesizing the sulfhydryl polyethylene glycol modified ruthenium nano material: 15mg of mercaptopolyethylene glycol (molecular weight 2000) and 2mg of ruthenium nanomaterial are added to 2ml of chloroform, sonicated in a water bath for 5min and stirred for a further 12h. And (3) carrying out spin steaming on the mixed solution for 1h at the temperature of 60 ℃, and adding 2ml of ultrapure water for hydration to obtain the sulfhydryl polyethylene glycol modified ruthenium nanomaterial.
As shown in FIG. 2, the ruthenium nano materials with three sizes can be stably dispersed in the aqueous solution, and the particle size is 5-40nm.
Example 3
Characterization of catalase-like properties of ruthenium nanomaterial: ruthenium nanomaterial (20. Mu.g/ml) and hydrogen peroxide (1 mM) were mixed in 5ml of ultrapure water, and the oxygen content in the solution was measured by a dissolved oxygen meter.
As shown in FIG. 3, the three-size ruthenium nanomaterial has catalase-like activity, and the activity of sRuNP is optimal.
Characterization of the properties of the superoxide dismutase-like ruthenium nanomaterial: first, a solution containing 1mM diethyl trimellitic anhydride and 0.4mM xanthine was prepared as solution A, and a solution containing 0.1U/ml xanthine oxidase was prepared as solution B. Mu.l of solution A, 25. Mu.l of ruthenium nanomaterial and 20. Mu.l of solution B were mixed and incubated for 1min, and 20. Mu.l of spin-trapping agent was added to detect the characteristic signal in an electron spin resonance apparatus.
As shown in FIG. 4, the three-size ruthenium nanomaterial has superoxide dismutase-like activity, and the activity of sRuNP is optimal.
Characterization of the performance of ruthenium nanomaterial to scavenge hydroxyl radicals: 70 μl of ferrous sulfate (0.735 mM) and 20 μl of hydrogen peroxide were mixed to generate hydroxyl radicals, 100 μl of ruthenium nanomaterial (20 g/ml) was added, and after incubation for 30s, 10 μl of spin-trap was added, and the characteristic signal was detected in an electron spin resonance apparatus.
As shown in fig. 5, the ruthenium nanomaterial of three sizes has the property of scavenging hydroxyl radicals, and the activity of srunop is optimal.
Quantitative analysis of cellular activity of ruthenium nanomaterial on normal hepatocytes: taking normal liver cells (HL 7702), preparing a solution with cell density of 8000cells/ml with fresh culture medium, inoculating into 96-well plate (100 μl), inoculating into 5% CO at 37deg.C 2 Is cultured in an incubator. After 24h of cell wall-attached culture, the culture medium was changed to one containing ruthenium nanomaterial of different concentrations and different sizes. The culture was continued for 24 hours, the medium was aspirated, then MTT solution was added to the 96-well plate, incubated at 37℃for 1-4 hours, the medium was aspirated, 200. Mu.l of dimethyl sulfoxide was added, and the absorbance was measured after shaking.
The results are shown in FIG. 6, and the ruthenium nanomaterial of three sizes has no obvious toxicity to normal liver cells. Quantitative analysis of cell activity of ruthenium nanomaterial to inhibit hydrogen peroxide-induced cell death: taking normal liver cells, preparing a solution with cell density of 8000cells/ml with fresh culture medium, inoculating into 96-well plate (100 μl), and inoculating into 5% CO at 37deg.C 2 Is cultured in an incubator. After 24h of cell attachment culture, the medium was changed to one containing hydrogen peroxide (200. Mu.M) and ruthenium nanomaterial of different concentrations and sizes. Continuously culturing for 24h, sucking out the culture medium, adding MTT solution into the 96-well plate, incubating for 1-4 h at 37 ℃, sucking out the culture medium, adding 200 μl of dimethyl sulfoxide, shaking, and measuringThe absorbance was determined.
As shown in FIG. 7, the hydrogen peroxide-induced cell death of the three-dimensional ruthenium nanomaterial was reversed to some extent, and the effects of sRuNP were optimal.
Effects of ruthenium nanomaterial on treatment of acetaminophen-induced liver injury: 20C 57BL/6 mice (male, 6-8 weeks) were randomly divided into 4 groups of 5. Control, phosphate Buffered Saline (PBS), N-acetylcysteine (NAC) and sRuNP (sRuNP), respectively. After 12h of fasting, acetaminophen (300 mg/kg) was intraperitoneally injected into the PBS, NAC and sRuNP groups, and after 6h PBS, NAC (300 mg/kg) and sRuNP (5 mg/kg) were intravenously injected, respectively. Blood was collected after 24h and serum glutamic pyruvic transaminase (ALT) and glutamic oxaloacetic transaminase (AST) levels were analyzed.
As shown in fig. 8, the mice treated with srunop had significantly lower ALT and AST levels than the PBS and NAC groups, and the surface srunop could be used to treat late acetaminophen-induced liver injury with better efficacy than NAC.
In a acetaminophen-induced liver injury mouse model, the ruthenium nanomaterial prepared by the invention can still have a good treatment effect after acetaminophen poisoning for six hours.
Claims (6)
1. The application of the ruthenium nano material in preparing the medicine for treating the oxidative stress related diseases is characterized in that the preparation method of the ruthenium nano material comprises the following steps: dissolving ruthenium chloride in ultrapure water, dissolving oleylamine in cyclohexane, mixing the two, performing hydrothermal reaction, and precipitating by a poor solvent after the reaction is finished to obtain a ruthenium nano material; the temperature of the hydrothermal reaction is 160 ℃; the feeding amount of ruthenium chloride is 40mg, and the feeding amount of oleylamine is 0.2g, 0.4g or 0.8 g;
the oxidative stress-related disease is acetaminophen-induced liver injury.
2. The use according to claim 1, wherein the reaction time is 0.5-72 h.
3. The use according to claim 1, wherein the ruthenium nanomaterial is sized from 1 to 20nm.
4. The use according to claim 1, wherein the preparation method comprises: and carrying out sulfhydryl polyethylene glycol modification on the ruthenium nanomaterial to obtain the sulfhydryl polyethylene glycol modified ruthenium nanomaterial.
5. The application of claim 1, wherein the mass feed ratio of the ruthenium nanomaterial to the sulfhydryl polyethylene glycol is 1:1-50.
6. The application of claim 4, wherein the hydraulic diameter of the sulfhydryl polyethylene glycol modified ruthenium nanomaterial is 2-40 nm.
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