CN109650449B - Preparation method of molybdenum oxide nano material, product and application - Google Patents
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Abstract
The invention relates to a preparation method of a molybdenum oxide nano material, a product and application, wherein the preparation method comprises the following steps: 1) dissolving molybdenum acetylacetonate in a mixed solution of octadecene, oleic acid and hexadecylamine, and stirring at 90-150 ℃ to react to generate a molybdenum oxide nano intermediate; 2) and (2) continuously carrying out hydrothermal reaction on the mixed solution containing the molybdenum oxide nano intermediate in the step 1) to obtain the sea urchin-shaped hollow molybdenum oxide nano material. The obtained molybdenum oxide nano material can realize specific toxicity activation at a tumor part for efficient imaging and treatment of tumors, and can be quickly degraded in normal tissues to ensure good biological safety.
Description
Technical Field
The invention relates to the field of preparation of molybdenum oxide, in particular to a preparation method of a molybdenum oxide nano material, a product and application.
Background
Tumors have become one of the major diseases that seriously threaten human health. According to the statistics of research reports of international agency for research on cancers (IARC) under the World Health Organization (WHO), newly-determined cases of cancer in 2018 all over the world are 1810 thousands of times, and the Asian region accounts for 48.4% of the world in newly-determined cancer patients.
At present, the tumor targeting efficiency of the anti-tumor nano material is still low (generally less than 1%), so that the tumor killing effect is poor, and the toxic and side effects on normal cells are obvious. Even if the mode of administration is intratumoral injection, the diffusion of the antitumor nanomaterial to surrounding normal tissues causes an unpredictable toxicity problem. The anti-tumor nano material (especially inorganic nano material) needs to be discharged out of the body through a renal route or a hepatobiliary route within a certain time, so as to ensure that the anti-tumor nano material can be quickly cleared in normal tissues, and further avoid the toxicity problem caused by long-term accumulation in the body. However, the requirements for the size, morphology, surface chemistry, etc. of the nanomaterial are high.
Therefore, many researchers have been dedicated to research novel anti-tumor nanomaterials to improve local cytotoxicity of tumors while ensuring safety in normal tissues. For example, CN 10142541B discloses a template-free, rapid and effective hydrothermal synthesis method, which uses molybdic peroxide prepared by reacting molybdenum trioxide with aqueous hydrogen peroxide as a precursor, and performs hydrothermal synthesis at 80-180 ℃ to obtain a dispersed a-molybdenum trioxide hydrate. Carrying out hydrothermal synthesis at 65-75 ℃ to obtain the peroxide modified molybdenum oxide hydrate. The hydrate is of a multi-scale structure, and the nano thin slice, the micro prism and the nano rod-shaped structure unit are divergently assembled into a micron-level high-density echinoid structure. However, the large size of this micron-sized molybdenum oxide limits its biological applications. In addition, CN 108451932A discloses pluronic-modified molybdenum oxide nanosheets, and a preparation method and application thereof, wherein the pluronic-modified molybdenum oxide nanosheets have good biological safety, strong photothermal conversion effect, high drug-loading capacity and pH-dependent biodegradability, and can be combined with near-infrared light irradiation to realize tumor photothermal therapy or chemotherapy-photothermal combined therapy, improve the tumor treatment effect and reduce toxic and side effects. However, the tissue attenuation properties of near-infrared light and poor patient compliance limit the widespread use of photothermal therapy.
Therefore, the development of an anti-tumor nano material with high tumor cell killing efficiency and good in vivo biosafety is urgently needed.
Disclosure of Invention
The invention aims to provide a preparation method of a molybdenum oxide nano material aiming at the defects of the prior art, the obtained molybdenum oxide nano material not only has strong light-heat conversion effect and drug-loading property, but also can specifically realize toxicity activation at a tumor part so as to realize efficient imaging and treatment of tumors, and in addition, the good biological safety is kept in normal tissues by virtue of quick degradation depending on pH.
The technical scheme provided by the invention is as follows:
a preparation method of a molybdenum oxide nano material comprises the following steps:
1) dissolving molybdenum acetylacetonate in a mixed solution of octadecene, oleic acid and hexadecylamine, and stirring at 90-150 ℃ to react to generate a molybdenum oxide nano intermediate;
2) and (2) continuously carrying out hydrothermal reaction on the mixed solution containing the molybdenum oxide nano intermediate in the step 1) to obtain the sea urchin-shaped hollow molybdenum oxide nano material.
The invention relates to a method for preparing acetyl acetone molybdenum, oleic acid and hexadecylamineGenerating a molybdenum oxide nano intermediate, and then continuously etching and reducing the molybdenum oxide nano intermediate by oleic acid and hexadecylamine in a hydrothermal reaction to obtain the sea urchin-shaped hollow molybdenum oxide nano material (MoO)3-xNUs). The particle size of the sea urchin-shaped hollow molybdenum oxide nano material is 100-1000 nm. The sea urchin thorn-shaped branches and the hollow cavities have larger specific surface areas, so that a large number of defect active sites are distributed on the surface of the sea urchin-shaped hollow molybdenum oxide nano material, and a large number of pentavalent molybdenum with reduction property is exposed on the surface of the material, thereby laying a material chemical foundation for specific toxicity activation of the sea urchin thorn-shaped branches and the hollow cavities at tumor sites.
The sea urchin-shaped hollow molybdenum oxide nano material has the particle size range convenient for the tumor cells to take, and after being taken by the tumor cells, the sea urchin-shaped hollow molybdenum oxide nano material can be matched with cells (pH) due to the special shape and structure of the sea urchin-shaped hollow molybdenum oxide nano material<7.4) high concentration of H2O2Reaction to form highly toxic superoxide anions (O)2 -) Activating cytotoxicity, which in turn leads to apoptosis of tumor cells. In normal physiological environment (pH 7.4), the sea urchin-shaped hollow molybdenum oxide nano material is preferentially mixed with OH-Reacts and is degraded into safe and nontoxic MoO4 2-And good biological safety is realized.
The feeding ratio of the molybdenum acetylacetonate, the oleic acid, the hexadecylamine and the octadecene is 10-400 mg: 0.2-20 ml: 0.02-2 g: 1-80 ml.
Preferably, the feeding ratio of the molybdenum acetylacetonate, the oleic acid, the hexadecylamine and the octadecene is 10-250 mg: 1-20 ml: 0.05-1.0 g: 4-40 ml.
The stirring reaction time in the invention is 5 min-4 h. Preferably, the stirring reaction in the step 1) is carried out at the temperature of 90-120 ℃ for 0.5-2 h.
The temperature of the hydrothermal reaction is 120-260 ℃, and the reaction time is 0.5-48 h.
Preferably, the sea urchin-shaped hollow molybdenum oxide nano material in the step 2) is obtained by precipitation of a poor solvent. Preferably, the poor solvent is selected from one or more of acetone, ethanol, ethyl acetate, methanol, methyl pyrrolidone, medium chain alcohol, acetonitrile, dimethylformamide and dimethyl sulfoxide.
The preparation method of the molybdenum oxide nano material comprises the following steps: and carrying out the loading of the micromolecular drug for treating the tumor on the sea urchin-shaped hollow molybdenum oxide nano material. The sea urchin-shaped hollow molybdenum oxide nano material is hollow, and the hollow cavity has a larger specific surface area, can load small-molecule drugs, and synergistically and remarkably improves the tumor treatment effect.
Preferably, the small molecule drug is selected from one or more of adriamycin, epidopoxin, vinblastine, vincristine, vinblastine, vinorelbine, paclitaxel, docetaxel, cabazitaxel, etoposide, teniposide, gemcitabine, irinotecan, camptothecin, hydroxycamptothecin, actinomycin, cytarabine, nimustine, carmustine, lomustine, semustine, fluorouracil, amide, ifosfamide, mendele, cisplatin, carboplatin and methotrexate.
The preparation method of the molybdenum oxide nano material comprises the following steps: and carrying out amphiphilic polymer modification on the sea urchin-shaped hollow molybdenum oxide nano material. Modifying the sea urchin-shaped hollow molybdenum oxide nano material by using amphiphilic macromolecules to convert lipophilicity into hydrophilicity, thereby obtaining the sea urchin-shaped hollow molybdenum oxide nano material dispersed in water.
Preferably, the amphiphilic polymer is selected from one or more of phospholipid-polyethylene glycol, poloxamer, polyvinylpyrrolidone, polyvinyl alcohol, tween, vitamin E polyethylene glycol succinate, polylactic acid-glycolic acid copolymer, polylactic acid, span, phospholipid, polyethylene glycol, sodium dodecyl sulfate, hexadecyl trimethyl ammonium bromide, albumin, lipoprotein, castor oil polyoxyethylene ether, fatty acid polyoxyethylene ester, fatty acid polyoxyethylene ether, alkylphenol polyoxyethylene ether and polyol ester.
Preferably, the amphiphilic polymer is selected from one or more of phospholipid-polyethylene glycol, poloxamer, polyvinylpyrrolidone, polyvinyl alcohol, tween, phospholipid, vitamin E polyethylene glycol succinate and polylactic acid-glycolic acid copolymer.
Preferably, the mass charge ratio of the sea urchin-shaped hollow molybdenum oxide nano material to the amphiphilic polymer is 1: 1-50.
The modification of the amphiphilic polymer adopts a film dispersion method or an emulsion solvent volatilization method.
Preferably, the thin film dispersion method includes: dispersing the sea urchin-shaped hollow molybdenum oxide nano material in a good solvent, stirring at room temperature, adding an amphiphilic polymer, decompressing, evaporating and hydrating to obtain the sea urchin-shaped hollow molybdenum oxide nano material dispersed in water.
Preferably, the emulsification solvent evaporation method comprises: dispersing the sea urchin-shaped hollow molybdenum oxide nano material in a good solvent, stirring at room temperature, adding into an amphiphilic polymer aqueous solution, performing ultrasonic treatment, and performing reduced pressure evaporation to obtain the sea urchin-shaped hollow molybdenum oxide nano material dispersed in water.
Preferably, the good solvent is one or more selected from tetrahydrofuran, dichloromethane, chloroform, n-hexane, cyclohexane and dioxane.
The invention also provides the molybdenum oxide nano material prepared by the preparation method. The particle size of the sea urchin-shaped hollow molybdenum oxide nano material is 100-1000 nm.
The invention also provides application of the molybdenum oxide nano material in preparation of antitumor drugs.
Compared with the prior art, the invention has the beneficial effects that:
(1) the preparation method has the advantages of mild reaction system, controllable conditions, low cost and good clinical transformation possibility.
(2) The molybdenum oxide nano material obtained in the invention can realize specific toxicity activation at a tumor part to realize efficient tumor treatment (without introducing external laser), and can be rapidly degraded in normal tissues to ensure good biological safety.
(3) The photoacoustic imaging performance of the molybdenum oxide nano material obtained in the invention is weakened along with degradation, and the tumor treatment effect and safety of the echinoid hollow molybdenum oxide nano material can be monitored through photoacoustic imaging.
(4) The molybdenum oxide nano material obtained in the invention has better drug loading performance, the hollow cavity has larger specific surface area, and small molecular drugs for treating tumors can be loaded in the sea urchin-shaped nano material, so that the tumor treatment effect is further improved. In addition, the molybdenum oxide nano material obtained in the invention still has strong light-heat conversion property, and can be used for treating tumors through light-heat treatment.
Drawings
FIG. 1 is a TEM image of a sea urchin-shaped hollow molybdenum oxide nanomaterial prepared in example 1;
FIG. 2 is a TEM image of a molybdenum oxide nano-intermediate prepared in example 3;
FIG. 3 is an XPS plot of a molybdenum oxide nano-intermediate prepared in example 3;
FIG. 4 is a TEM image of the urchin-shaped hollow molybdenum oxide nanomaterial prepared in example 3;
FIG. 5 is an XPS plot of the urchin-shaped hollow molybdenum oxide nanomaterial prepared in example 3;
FIG. 6 is a drug loading performance evaluation chart of the sea urchin-shaped hollow molybdenum oxide nanomaterial prepared in example 6;
FIG. 7 is a graph showing the evaluation of the efficiency of generating superoxide anions in the sea urchin-shaped hollow molybdenum oxide nanomaterial of example 3;
FIG. 8 is a graph showing evaluation of the efficiency of generating superoxide anions by degradation products of the sea urchin-shaped hollow molybdenum oxide nanomaterial in the comparative example;
FIG. 9 is a graph showing the evaluation of cytotoxicity of the sea urchin-like hollow molybdenum oxide nanomaterial of example 3 against tumor cells under the environments of pH6.0 and pH 7.4;
FIG. 10 is a graph showing the cytotoxicity evaluation of the degradation products of the sea urchin-like hollow molybdenum oxide nanomaterial of the comparative example against tumor cells under the environment of pH6.0 and pH7.4;
FIG. 11 is a graph showing the evaluation of the in vivo antitumor effect of the echinoid hollow molybdenum oxide nanomaterial of example 3.
Detailed Description
The invention is explained in detail below with reference to specific embodiments and the attached drawing of the description.
Example 1
(1) 80mg of molybdenum acetylacetonate, 0.2g of hexadecylamine and 2ml of oleic acid are dispersed in 8ml of octadecene, and the mixture is heated and stirred at 100 ℃ for reaction for 10min to generate a molybdenum oxide nano intermediate.
(2) Transferring the mixture obtained in the step (1) into a high-pressure hydrothermal kettle with the volume of 15ml, heating to 200 ℃, reacting for 12 hours, taking out the hydrothermal kettle, cooling to room temperature, centrifuging ethanol, collecting precipitate, and centrifuging to obtain the sea urchin-shaped hollow molybdenum oxide nano material (MoO)3-xNUs), and is dispersed in chloroform after 3 washes with anhydrous ethanol.
The sea urchin-shaped hollow molybdenum oxide nano material is subjected to shape representation by using a TEM, and the result is shown in figure 1, wherein the particle size is 300-500 nm.
Example 2
(1) 100mg of molybdenum acetylacetonate, 0.2g of hexadecylamine and 2ml of oleic acid are dispersed in 8ml of octadecene, and the mixture is heated and stirred at 120 ℃ for reaction for 10min to generate a molybdenum oxide nano intermediate.
(2) Transferring the mixture obtained in the step (1) into a high-pressure hydrothermal kettle with the volume of 15ml, heating to 180 ℃, reacting for 12 hours, taking out the hydrothermal kettle, cooling to room temperature, centrifuging ethanol, collecting precipitate, and centrifuging to obtain the sea urchin-shaped hollow molybdenum oxide nano material (MoO)3-xNUs), washing with absolute ethyl alcohol for 3 times, and dispersing in chloroform to obtain the sea urchin-shaped hollow molybdenum oxide nano material with the size of 300-600 nm.
Example 3
(1) Dispersing 120mg of molybdenum acetylacetonate, 0.2g of hexadecylamine and 4ml of oleic acid in 8ml of octadecene, heating and stirring at 100 ℃ for reacting for 20min to generate a molybdenum oxide nano intermediate.
And respectively carrying out TEM and XPS characterization on the intermediate product molybdenum oxide nano intermediate. The TEM characterization is shown in FIG. 2, and the intermediate product is proved to be nano-scale particles with the particle size of 200-400 nm. XPS characterization as shown in figure 3, demonstrated that a portion of the hexavalent molybdenum had been reduced to pentavalent molybdenum during the heating process.
(2) And (2) transferring the mixture obtained in the step (1) into a high-pressure hydrothermal kettle with the volume of 15ml, heating to 160 ℃, reacting for 12 hours, taking out the hydrothermal kettle, cooling to room temperature, centrifuging with ethanol, collecting precipitate, centrifuging to obtain a sea urchin-shaped hollow molybdenum oxide nano material, washing with absolute ethanol for 3 times, and dispersing in chloroform.
And respectively carrying out TEM and XPS characterization on the sea urchin-shaped hollow molybdenum oxide nano material, wherein the TEM characterization is shown in figure 4, and the size of the obtained sea urchin-shaped hollow molybdenum oxide nano material is 300-600 nm. The XPS characterization is shown in FIG. 5, and the pentavalent molybdenum content in the obtained sea urchin-shaped hollow molybdenum oxide nano material is up to 47%.
(3) Sea urchin-shaped hollow molybdenum oxide nano material and phospholipid-polyethylene glycol polymer (1: 10, g/g) are dispersed in chloroform. And (3) carrying out rotary evaporation for 1h to remove the organic solvent, then adding physiological saline to disperse in water bath ultrasound to obtain the sea urchin-shaped hollow molybdenum oxide nano material with good dispersion in water, and centrifuging at a high speed to remove the redundant surfactant.
Example 4
(1) Dispersing 120mg of molybdenum acetylacetonate, 0.2g of hexadecylamine and 4ml of oleic acid in 8ml of octadecene, heating and stirring at 100 ℃ for reacting for 20min to generate a molybdenum oxide nano intermediate.
(2) And (2) transferring the mixture obtained in the step (1) into a high-pressure hydrothermal kettle with the volume of 15ml, heating to 160 ℃, reacting for 6 hours, taking out the hydrothermal kettle, cooling to room temperature, centrifuging with ethanol, collecting precipitate, centrifuging to obtain a sea urchin-shaped hollow molybdenum oxide nano material, washing with absolute ethanol for 3 times, and dispersing in chloroform.
(3) Sea urchin-shaped hollow molybdenum oxide nano material and polyethylene glycol 1000 vitamin E succinate (1: 10, g/g) are dispersed in chloroform. And (3) carrying out rotary evaporation for 1h to remove the organic solvent, then adding physiological saline to disperse in water bath ultrasound to obtain the sea urchin-shaped hollow molybdenum oxide nano material with good dispersion in water, and centrifuging at a high speed to remove the redundant surfactant.
Example 5
(1) Dispersing 120mg of molybdenum acetylacetonate, 0.2g of hexadecylamine and 4ml of oleic acid in 8ml of octadecene, heating and stirring at 100 ℃ for reacting for 20min to generate a molybdenum oxide nano intermediate.
(2) And (2) transferring the mixture obtained in the step (1) into a high-pressure hydrothermal kettle with the volume of 15ml, heating to 160 ℃, reacting for 6 hours, taking out the hydrothermal kettle, cooling to room temperature, centrifuging with ethanol, collecting precipitate, centrifuging to obtain a sea urchin-shaped hollow molybdenum oxide nano material, washing with absolute ethanol for 3 times, and dispersing in chloroform.
(3) Sea urchin-shaped hollow molybdenum oxide nano material and polyvinyl alcohol (1: 10, g/g) are dispersed in chloroform. And (3) carrying out rotary evaporation for 1h to remove the organic solvent, then adding physiological saline to disperse in water bath ultrasound to obtain the sea urchin-shaped hollow molybdenum oxide nano material with good dispersion in water, and centrifuging at a high speed to remove the redundant surfactant.
Example 6
(1) 40mg of molybdenum acetylacetonate, 0.2g of hexadecylamine and 4ml of oleic acid are dispersed in 8ml of octadecene, and the mixture is heated and stirred at 100 ℃ for reaction for 10min to generate a molybdenum oxide nano intermediate.
(2) And (2) transferring the mixture obtained in the step (1) into a high-pressure hydrothermal kettle with the volume of 15ml, heating to 180 ℃, reacting for 6 hours, taking out the hydrothermal kettle, cooling to room temperature, centrifuging with ethanol, collecting precipitate, centrifuging to obtain a sea urchin-shaped hollow molybdenum oxide nano material, washing with absolute ethanol for 3 times, and dispersing in chloroform to obtain the sea urchin-shaped hollow molybdenum oxide nano material with the size of 200-400 nm.
(3) The sea urchin-shaped hollow molybdenum oxide nano material and adriamycin (1: 5, g/g) after hydrochloric acid removal are dispersed in chloroform, stirred at room temperature in a dark place for 24 hours, and then centrifuged to remove free adriamycin.
(4) Subsequently, dispersing the adriamycin-loaded sea urchin-shaped hollow molybdenum oxide nano material and polyvinylpyrrolidone 5000 (1: 10, g/g) in chloroform, performing rotary evaporation for 1h to remove the organic solvent, adding physiological saline, and dispersing in water bath ultrasound to obtain the adriamycin-loaded sea urchin-shaped hollow molybdenum oxide nano material (MoO) with good water dispersion3-xNUs/DOX), and high speed centrifugation to remove excess surfactant.
By pairing MoO's by UV-visible spectrophotometer3-xNUs/DOX, as shown in FIG. 6, it can be seen that DOX was successfully loaded into the sea urchin-shaped hollow molybdenum oxide nanomaterial.
Comparative example
(1) Dispersing 120mg of molybdenum acetylacetonate, 0.2g of hexadecylamine and 4ml of oleic acid in 8ml of octadecene, heating and stirring at 100 ℃ for reacting for 20min to generate a molybdenum oxide nano intermediate.
(2) And (2) transferring the mixture obtained in the step (1) into a high-pressure hydrothermal kettle with the volume of 15ml, heating to 160 ℃, reacting for 12 hours, taking out the hydrothermal kettle, cooling to room temperature, centrifuging with ethanol, collecting precipitate, centrifuging to obtain a sea urchin-shaped hollow molybdenum oxide nano material, washing with absolute ethanol for 3 times, and dispersing in chloroform. The size of the obtained sea urchin-shaped hollow molybdenum oxide nano material is 200-400 nm.
(3) Dispersing sea urchin-shaped hollow molybdenum oxide nano material and phospholipid-polyethylene glycol polymer (1: 10, g/g) in chloroform, performing rotary evaporation for 1h to remove organic solvent, adding NaOH solution (1M), dispersing in water bath ultrasound to obtain well-dispersed sea urchin-shaped hollow molybdenum oxide nano material, and centrifuging at high speed to remove redundant surfactant.
(4) And (3) putting the sea urchin-shaped hollow molybdenum oxide nano material dispersed in the NaOH solution in an oven at 60 ℃ for 24 hours to completely degrade, and freeze-drying to obtain degradation product powder.
Performance testing
(1) In vitro evaluation of superoxide anions
(1.1) 20. mu.l of an ethanol solution of DPBF (10mM), 1. mu. l H2O2The solution (2M), sea urchin-like hollow molybdenum oxide nanomaterial (prepared in example 3, 20 μ g) was dispersed in a water/ethanol mixed solution (water: ethanol ═ 4:6, v/v).
O-of sea urchin-like hollow molybdenum oxide nanomaterial investigation by UV-visible spectrophotometer at different times (0, 2, 5, 10, 20 and 30min)2-The yield, as shown in FIG. 7, is that the rapid decrease in the absorbance of DPBF indicates that the urchin-like hollow molybdenum oxide nanomaterial is highly contaminated with O2-Yield.
(1.2) 20. mu.l of ethanol solution of DPBF (10mM), 1. mu. l H2O2The solution (2M), degradation products of sea urchin-like hollow molybdenum oxide nanomaterial (prepared in comparative example, 20 μ g) were dispersed in a water/ethanol mixed solution (water: ethanol ═ 4:6, v/v).
Passing through UV-visible spectrophotometer at different times (0, 2, 5, 10, 20 and 30min)) Study of the degradation products of the sea urchin-like hollow molybdenum oxide nanomaterial2-The yield, as shown in FIG. 8, was such that the substantial invariance of the absorbance of DPBF indicated that the degradation products were not rendered to be O-vented2-The ability of the cell to perform.
(1.3) comparing FIGS. 7 and 8, it can be seen that the sea urchin-like structure (rich in multi-defect sites) and valence (pentavalent molybdenum) pairs of the sea urchin-like hollow molybdenum oxide nanomaterial with H2O2Reaction and generation of O2-The process of (2) is very critical.
(2) Evaluation of cytotoxicity against melanoma cancer cell lines
Melanin cancer cells (B16 cells) in logarithmic growth phase were collected and their cell density was adjusted to 1X 10 with fresh medium4cells/ml, seeded in 96-well plates (200. mu.l/well) at 37 ℃ in 5% CO2Culturing in the incubator.
After 12h of cell adherent culture, the cells were changed to sea urchin-shaped hollow molybdenum oxide nanomaterial (prepared according to the method of example 3) and degradation product of sea urchin-shaped hollow molybdenum oxide nanomaterial (prepared according to the method of the present comparative example) at different pH (pH6.0 and pH7.4) and Mo concentrations of 0, 1.56, 3.13, 6.25 and 12.50. mu.g/ml. The incubation was continued for 24h, and the medium was aspirated and washed with 200. mu.l PBS. Then adding MTT solution (200 mul/well) into 96-well plates, incubating for 1-4 h at 37 ℃, sucking out the culture solution, adding 200 mul DMSO, shaking uniformly, and measuring the optical density OD value.
And (4) processing data, namely processing the data by using corresponding software of a microplate reader, calculating an average value of OD values of 5 holes of each sample, and calculating the Cell survival rate (Cell Viability%) by using the average value according to the following formula.
Cell Viability% (% OD) of sample group/blank group OD value × 100% (Cell Viability% (% OD)sample/ODcontrol×100％)
The results are shown in FIGS. 9 and 10. As shown in figure 9, the sea urchin-shaped hollow molybdenum oxide nano material has high cytotoxicity at pH6.0, but has no obvious cytotoxicity at pH7.4; as can be seen from FIG. 10, the degradation products are not significantly cytotoxic. Therefore, the sea urchin-shaped hollow molybdenum oxide nano material has high toxicity in a tumor cell micro-acid environment, and can be degraded into a safe and nontoxic product in a neutral environment.
(3) Evaluation of cytotoxicity against melanoma cancer cell lines
Twelve nude mice were randomly divided into 2 groups of 6 mice each. Respectively physiological saline group and sea urchin-shaped hollow molybdenum oxide nano material (MoO)3-xNUs) (prepared according to the procedure of example 3). Intratumoral administration was twice weekly. Tumor volume (V) was measured every other day and calculated as: v ═ lxw2And/2, W and L are the widest and longest radial line lengths of the tumor, respectively. Tumor volume changes were monitored using tumor volume versus original volume.
The result is shown in figure 11, and it can be known that the sea urchin-shaped hollow molybdenum oxide nano material can obviously inhibit the growth of tumor under the condition of no exogenous laser or drug loading.
The above embodiments are described in detail to explain the technical solutions and advantages of the present invention, and it should be understood that the above embodiments are only specific examples of the present invention and are not intended to limit the present invention, and any modifications, additions, equivalents, etc. made within the scope of the principles of the present invention should be included in the scope of the present invention.
Claims (7)
1. A preparation method of a molybdenum oxide nano material is characterized by comprising the following steps:
1) dissolving molybdenum acetylacetonate in a mixed solution of octadecene, oleic acid and hexadecylamine, and stirring at 90-150 ℃ to react to generate a molybdenum oxide nano intermediate;
2) continuously carrying out hydrothermal reaction on the mixed solution containing the molybdenum oxide nano intermediate in the step 1) to obtain a sea urchin-shaped hollow molybdenum oxide nano material; the particle size of the sea urchin-shaped hollow molybdenum oxide nano material is 100-1000 nm;
the feeding ratio of the molybdenum acetylacetonate to the oleic acid to the hexadecylamine to the octadecene is 10-400 mg: 0.2-20 ml: 0.02-2 g: 1-80 ml;
the temperature of the hydrothermal reaction is 120-260 ℃, and the reaction time is 0.5-48 h;
and carrying out amphiphilic polymer modification on the sea urchin-shaped hollow molybdenum oxide nano material.
2. The method for preparing the molybdenum oxide nanomaterial according to claim 1, wherein the stirring reaction time is 5min to 4 hours.
3. The method for preparing the molybdenum oxide nanomaterial according to claim 1, comprising: and carrying out the loading of the micromolecular drug for treating the tumor on the sea urchin-shaped hollow molybdenum oxide nano material.
4. The preparation method of the molybdenum oxide nanomaterial according to claim 1, wherein the mass charge ratio of the sea urchin-shaped hollow molybdenum oxide nanomaterial to the amphiphilic polymer is 1: 1-50.
5. The method for preparing a molybdenum oxide nanomaterial according to claim 1, wherein the amphiphilic polymer is modified by a thin film dispersion method or an emulsion solvent evaporation method.
6. The molybdenum oxide nano material prepared by the preparation method of any one of claims 1 to 5.
7. The use of the molybdenum oxide nanomaterial of claim 6 in the preparation of an anti-tumor medicament.
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| CN103950994A (en) * | 2014-05-13 | 2014-07-30 | 中南大学 | Method for preparing double-shell CoO/Co3O4 hollow nanoparticles |
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