CN106860427B - Cerium oxide/iron oxide/mesoporous silicon nano composite material and preparation method and application thereof - Google Patents
Cerium oxide/iron oxide/mesoporous silicon nano composite material and preparation method and application thereof Download PDFInfo
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Abstract
The invention relates to a cerium oxide/ferric oxide/mesoporous silicon nano composite material, wherein a ligand-converted cerium oxide nanocrystal and a ligand-converted ferric oxide nanocrystal are respectively modified on the surface of a mesoporous silicon nano particle modified by an amino group. The invention also relates to a preparation method and application of the cerium oxide/iron oxide/mesoporous silicon nanocomposite. The composite material can carry AD treatment drugs, can remove ROS in AD-like cells, can be used as a nuclear magnetic resonance imaging contrast agent for AD diagnosis, and realizes diagnosis and treatment integration of AD.
Description
Technical Field
The invention belongs to the field of preparation of composite materials, and particularly relates to a cerium oxide/iron oxide/mesoporous silicon nano composite material as well as a preparation method and application thereof.
Background
Alzheimer's Disease (AD), also known as senile dementia, is a neurodegenerative disease caused by the state of impairment of intelligence such as language, memory and reasoning in the cerebral hemisphere, is one of the most prevalent diseases in the elderly population, and seriously harms human health. The 2005 results of world epidemiological investigations show that 2430 million patients with Alzheimer's disease are present worldwide, with 460 million new cases each year (1 new patient every 7 seconds). And this number increases 1 fold every 20 years, to 2040 years, with a total of up to 8110 million possible, with most patients concentrated in developing countries. According to the prediction, the number of patients suffering from Alzheimer's disease in China will increase by 3 times from 2001 to 2040, and at that time, the number of patients suffering from Alzheimer's disease in China will reach 1500 ten thousand, which becomes a serious social problem.
since 1906, the first cases of patients with alzheimer's disease have been discovered so far for over a hundred years. In centuries, although humans have been deeply aware of the pathogenesis and pathogenesis of alzheimer's disease, the lack of effective treatment for alzheimer's disease is a fact that humans are not contended. There are several hypotheses that currently involve many factors for their pathogenesis, and these theories partially explain the pathogenesis of AD. Aiming at different targets of the pathogenesis of AD, a plurality of varieties of AD treatment medicines appear. 1. Anti-amyloid beta protein: a beta-gamma-cleaving enzyme inhibitor aimed at inhibiting production of a beta; anti-aggregation drugs (including metal chelators) aimed at inhibiting a β aggregation; and protease activity-regulating drugs and immunotherapy aimed at the elimination of A.beta.. 2. Anti-tau protein phosphorylation: an inhibitor of Tau aggregation to inhibit the conversion of Tau protein to oligomers and fibrils; a phosphokinase inhibitor for inhibiting phosphorylation of Tau protein. In addition, research finds that reactive oxygen Radicals (ROS) also have a certain promotion effect on the formation of AD, so that the medicine for resisting oxidative stress is also one of the treatment targets of AD.
In addition to the lack of effective therapeutic approaches, no markers specific for clinical diagnosis of AD have been found to date. The definite diagnosis of AD depends on pathological diagnosis for a long time, and besides pathological diagnosis, correct diagnosis before birth is impossible, and clinical misdiagnosis can reach 27-57%. The above-mentioned problems are certainly solved if multi-target combination therapy can be administered while accurately diagnosing AD, and therefore, it is very important to construct a diagnosis and treatment integrated preparation.
With the rapid development of nanotechnology, new hope is brought to the integration of AD diagnosis and treatment. A stable, efficient and safe nano-carrier is constructed by optimizing materials, and a multifunctional nano-system integrating functions of drug targeted transportation, living body tracing, drug treatment, prognosis monitoring and the like is combined by utilizing the nano-carrier and combining a novel AD treatment drug and a high-accuracy AD diagnosis probe is expected to be a future research trend.
Disclosure of Invention
The invention aims to provide a cerium oxide/iron oxide/mesoporous silicon nanocomposite material, and a preparation method and application thereof, aiming at the defects of the prior art.
The technical scheme provided by the invention is as follows:
A cerium oxide/ferric oxide/mesoporous silicon nano composite material is characterized in that a ligand-converted cerium oxide nanocrystal and a ligand-converted ferric oxide nanocrystal are respectively modified on the surfaces of amino-modified mesoporous silicon nano particles.
In the technical scheme, the provided cerium oxide/iron oxide/mesoporous silicon nanocomposite can carry AD treatment drugs, remove ROS in AD-like nerve cells, has the function of a nuclear magnetic resonance imaging contrast agent, and realizes diagnosis and treatment integration of AD.
Firstly, the mesoporous silicon nano particles have extremely large pore volume, can carry AD treatment drugs and are continuously released at a pathological change part to achieve a treatment effect; secondly, the cerium oxide nanocrystal can balance raised active oxygen free radicals in AD-like nerve cells, so that oxidative stress injury caused by the active oxygen free radicals is reduced; the iron oxide nanocrystal has good nuclear magnetic resonance imaging effect, enhances the nuclear magnetic signal of a pathological change part, and is used for diagnosing AD.
Preferably, the ligand conversion is ligand conversion using 2-bromoisobutyric acid. In order to connect the cerium oxide nanocrystal and the iron oxide nanocrystal to the surface of the mesoporous silicon nanoparticle in a stable covalent bond mode, the cerium oxide nanocrystal is subjected to ligand conversion by using 2-bromoisobutyric acid, and then the surface of the mesoporous silicon nanoparticle is subjected to amino modification, so that the composition of the cerium oxide nanocrystal and the mesoporous silicon nanoparticle is facilitated, and finally, the three materials are compounded to realize multifunction integration.
Preferably, the particle size of the ligand-converted cerium oxide nanocrystal is 1-10 nm; the particle size of the ligand-converted iron oxide nanocrystal is 1-10 nm; the particle size of the amino-modified mesoporous silicon nanoparticles is 5-500 nm. The particle size range is convenient for cerium oxide nanocrystals and iron oxide nanocrystals to be uniformly modified on the surface of the mesoporous silicon nanoparticles, so that the composite material with excellent appearance and performance is obtained.
The invention provides a preparation method of the cerium oxide/iron oxide/mesoporous silicon nanocomposite material, which comprises the following steps:
1) Adding cerium acetate and oleylamine into dimethylbenzene for reaction to obtain cerium oxide nanocrystal; performing ligand conversion by using 2-bromoisobutyric acid to obtain ligand-converted cerium oxide nanocrystal;
2) adding iron oleate, oleic acid and oleyl alcohol into octadecene for reaction to obtain iron oxide nanocrystal; performing ligand conversion by using 2-bromoisobutyric acid to obtain ligand-converted iron oxide nanocrystals;
3) Dissolving hexadecyl trimethyl ammonium chloride and triethanolamine in water, reacting for 0.5-5 h at 90-100 ℃, and continuously adding tetraethoxysilane and 3-aminopropyl triethoxysilane for reacting for 0.5-5 h to obtain amino modified mesoporous silicon nanoparticles;
4) Adding the ligand-converted cerium oxide nanocrystal, the ligand-converted iron oxide nanocrystal and the amino-modified mesoporous silicon nanoparticles into N-N dimethylformamide, and reacting at 5-60 ℃ for 3-15 h to obtain the cerium oxide/iron oxide/mesoporous silicon nanocomposite.
By adopting the preparation method, the cerium oxide/iron oxide/mesoporous silicon nano composite material can be prepared, can carry AD treatment drugs, can remove ROS in AD-like nerve cells, and can be used as a nuclear magnetic resonance imaging contrast agent for AD diagnosis. Therefore, the diagnosis and treatment integrated preparation aiming at AD is constructed by compounding a plurality of materials.
Preferably, the mass ratio of the cerium acetate to the oleylamine in the step 1) is 1: 7-9.
preferably, in the step 1), the cerium acetate hydrate and oleylamine are added into xylene, and the mixture is reacted for 3-6 hours at 85-95 ℃, cooled, precipitated and washed to obtain the cerium oxide nanocrystal.
Preferably, the ligand conversion in step 1) refers to: and sequentially adding the obtained cerium oxide nanocrystal, 2-bromoisobutyric acid and citric acid into a mixed solvent of chloroform and N-N dimethylformamide, and stirring for 2-30 h. The ligand conversion is to connect the cerium oxide nanocrystal to the surface of the mesoporous silicon nanoparticle in a stable covalent bond mode. Further preferably, the mass ratio of the 2-bromoisobutyric acid to the cerium oxide nanocrystal in the step 1) is 20-60: 1.
Preferably, the mass ratio of the ferric oleate, the oleic acid, the oleyl alcohol and the octadecene in the step 2) is 1: 0.15-0.6: 0.5-2: 2.5 to 10.
Preferably, in the step 2), iron oleate, oleic acid and oleyl alcohol are added into octadecene, and the mixture reacts for 30-60 min at the temperature of 200-300 ℃, and then is cooled, precipitated and washed to obtain the iron oxide nanocrystal.
preferably, the ligand conversion in step 2) refers to: and sequentially adding the obtained iron oxide nanocrystal, 2-bromoisobutyric acid and citric acid into a mixed solvent of chloroform and N-N dimethylformamide, and stirring for 2-30 h. The ligand conversion is to connect the iron oxide nanocrystal to the surface of the mesoporous silicon nanoparticle in a stable covalent bond mode. Further preferably, the mass ratio of the 2-bromoisobutyric acid to the iron oxide nanocrystal in the step 1) is 20-60: 1.
Preferably, the charging ratio of the hexadecyl trimethyl ammonium chloride, the triethanolamine, the ethyl orthosilicate and the 3-aminopropyl triethoxysilane in the step 3) is as follows: 1.5-2.5 g: 0.03-0.05 g: 1.4-1.6 ml: 0.14-0.16 ml.
Preferably, the mass ratio of the ligand-converted cerium oxide nanocrystal, the ligand-converted iron oxide nanocrystal and the amino-modified mesoporous silicon nanoparticle in the step 4) is 1-5: 1-5: 1 to 15. The content of the ligand-converted cerium oxide nanocrystal and the content of the ligand-converted iron oxide nanocrystal are controlled by regulating the mass ratio of the three, so that the ligand-converted cerium oxide nanocrystal and the ligand-converted iron oxide nanocrystal are easy to modify on the surface of the amino modified mesoporous silicon nanoparticle, and the morphology is convenient to regulate.
The invention also provides application of the cerium oxide/iron oxide/mesoporous silicon nanocomposite material in preparation of anti-Alzheimer's disease drugs. The cerium oxide/iron oxide/mesoporous silicon nanocomposite can carry AD therapeutic drugs.
Preferably, the AD therapeutic drug is one or more of a beta-gamma-lyase inhibitor, a protease activity regulating drug, an immunotherapy drug, a Tau aggregation inhibitor and a Tau hyperphosphorylation inhibitor.
preferably, the anti-alzheimer's disease drug is a drug targeting Tau protein. After the cerium oxide/iron oxide/mesoporous silicon nano composite material carries a drug taking Tau protein as a target spot, the active oxygen free radicals can be eliminated, Tau protein phosphorylation is reduced, and neuronal death is inhibited.
Compared with the prior art, the invention has the beneficial effects that:
(1) the cerium oxide/ferric oxide/mesoporous silicon nano composite material can carry AD treatment drugs, can remove ROS in AD-like cells, and can be used as a nuclear magnetic resonance imaging contrast agent for AD diagnosis.
(2) The preparation method has mild reaction system and controllable conditions, and the prepared materials have good biocompatibility and good clinical transformation possibility.
Drawings
FIG. 1 is an XRD pattern of the ligand-converted cerium oxide nanocrystals, ligand-converted iron oxide nanocrystals and cerium oxide/iron oxide/mesoporous silicon nanocomposite in example 1;
FIG. 2 is a TEM photograph of ligand-converted cerium oxide nanocrystal a and ligand-converted iron oxide nanocrystal b in example 1;
FIG. 3 is a TEM photograph of the amino-modified mesoporous silicon nanoparticles of example 1;
FIG. 4 is a TEM photograph of the cerium oxide/iron oxide/mesoporous silicon nanocomposite in example 1;
FIG. 5 is a diagram showing the result of quantitative analysis of the activity of the SH-SY5Y cell biocompatible CCK-8 cell by using cerium oxide/iron oxide/mesoporous silicon/methylene blue nano composite materials with different concentrations in the application example;
FIG. 6 is a diagram showing the result of the CCK-8 cell activity quantitative analysis of the cerium oxide/iron oxide/mesoporous silicon/methylene blue nano composite materials with different concentrations in the application example for inhibiting OA-induced SH-SY5Y cell death.
Detailed Description
The invention is further described with reference to the following specific embodiments and the accompanying drawings.
Example 1
(1) Synthesis and ligand conversion of cerium oxide nanocrystals: adding 0.4g of cerium acetate hydrate and 3.2g of oleylamine into 15ml of dimethylbenzene, stirring for 4 hours at room temperature, and raising the temperature to 90 ℃ at a heating rate of 2 ℃ per minute; injecting 1ml of deionized water into an inert gas protection reaction system, aging for three hours, precipitating with acetone, and centrifuging to obtain the cerium oxide nanocrystal.
And (3) adding 15mg of the synthesized cerium oxide nanocrystal, 0.5g of 2-bromoisobutyric acid and 0.05g of citric acid into a mixed solvent of 7.5ml of chloroform and 7.5ml of N, N-dimethylformamide in sequence, and stirring for 24 hours to obtain the cerium oxide nanocrystal.
Subjecting the obtained ligand-converted cerium oxide nanocrystals to X-ray diffraction, as shown in FIG. 1; and the appearance of the ligand-converted cerium oxide nanocrystals was characterized by a transmission electron microscope, as shown in fig. 2 a.
(2) synthesis and ligand conversion of iron oxide nanocrystals: 1.8g of iron oleate, 0.6g of oleic acid, 1.6g of oleyl alcohol were added to 10g of octadecene. The mixture was stirred at room temperature and heated to 280 ℃ at a rate of 10 ℃ per minute. Maintaining the temperature for 30 minutes, cooling to room temperature, precipitating with acetone, and centrifuging to obtain the iron oxide nanocrystal.
15mg of the iron oxide nanocrystal obtained by synthesis, 0.5g of 2-bromoisobutyric acid and 0.05g of citric acid were sequentially added to a mixed solvent of 7.5ml of chloroform and 7.5ml of N, N-dimethylformamide and stirred for 24 hours to obtain the iron oxide nanoparticle.
Subjecting the obtained ligand-converted cerium oxide nanocrystals to X-ray diffraction, as shown in FIG. 1; and the appearance of the ligand-converted cerium oxide nanocrystals was characterized by transmission electron microscopy, as shown in fig. 2 b.
(3) Synthesis of amino-modified mesoporous silica nanoparticles: adding 2g of hexadecyl trimethyl ammonium chloride and 0.02g of triethanolamine into 20ml of deionized water, stirring and heating to 95 ℃, adding 1.5ml of tetraethoxysilane and 150 mu L of 3-aminopropyl triethoxysilane, and stirring and reacting for 1 h. The amino modified mesoporous silicon nano-particles can be obtained by centrifuging and washing away the template agent by 1 wt% of sodium chloride methanol solution.
The prepared amino modified mesoporous silicon nanoparticles are subjected to appearance characterization by a transmission electron microscope, as shown in fig. 3.
(4) Synthesis of cerium oxide/iron oxide/mesoporous silicon nanocomposite: reacting 2.5ml of N, N-dimethylformamide solution with ligand conversion concentration of 3mg/ml of cerium oxide nanocrystal, 5ml of N, N-dimethylformamide solution with ligand conversion concentration of 3mg/ml of cerium oxide nanocrystal and 10ml of N, N-dimethylformamide solution with 5mg/ml of amino-modified mesoporous silicon dioxide nanoparticles at 30 ℃ for 12 hours to obtain the cerium oxide/iron oxide/mesoporous silicon nanocomposite.
The obtained cerium oxide/iron oxide/mesoporous silicon nanocomposite is analyzed by a transmission electron microscope, and the obtained result is shown in figure 4, wherein the diameter of the cerium oxide/iron oxide/mesoporous silicon nanocomposite is 50-60 nm.
Example 2
(1) synthesis and ligand conversion of cerium oxide nanocrystals: adding 0.4g of cerium acetate hydrate and 3.6g of oleylamine into 15ml of dimethylbenzene, stirring for 6 hours at room temperature, and raising the temperature to 95 ℃ at a heating rate of 2 ℃ per minute; injecting 1ml of deionized water into an inert gas protection reaction system, aging for three hours, precipitating with acetone, and centrifuging to obtain the cerium oxide nanocrystal.
10mg of the synthesized cerium oxide nanocrystal, 0.5g of 2-bromoisobutyric acid and 0.05g of citric acid were sequentially added to a mixed solvent of 7.5ml of chloroform and 7.5ml of N, N-dimethylformamide and stirred for 12 hours to obtain the cerium oxide nanocrystal.
(2) Synthesis and ligand conversion of iron oxide nanocrystals: 2g of iron oleate, 1g of oleic acid, 2g of oleyl alcohol were added to 10g of octadecene. The mixture was stirred at room temperature and heated to 300 ℃ at a rate of 10 ℃ per minute. Maintaining the temperature for 40 minutes, cooling to room temperature, precipitating with acetone, and centrifuging to obtain the iron oxide nanocrystal.
10mg of iron oxide nanocrystal obtained by synthesis, 0.5g of 2-bromoisobutyric acid and 0.05g of citric acid were sequentially added to a mixed solvent of 7.5ml of chloroform and 7.5ml of N, N-dimethylformamide and stirred for 12 hours to obtain the iron oxide nanoparticle.
(3) Synthesizing amino modified mesoporous silicon nanoparticles: 2.4g of hexadecyltrimethylammonium chloride and 0.05g of triethanolamine were added to 20ml of deionized water, stirred and heated to 95 ℃, and 1.4ml of tetraethoxysilane and 160. mu.L of 3-aminopropyltriethoxysilane were added and stirred to react for 0.5 hour. The amino modified mesoporous silicon nano-particles can be obtained by centrifuging and washing away the template agent by 1 wt% of sodium chloride methanol solution.
(4) Synthesis of cerium oxide/iron oxide/mesoporous silicon nanocomposite: and reacting 3ml of N, N-dimethylformamide solution with ligand conversion concentration of 3mg/ml cerium oxide nanocrystal, 6ml of N, N-dimethylformamide solution with ligand conversion concentration of 3mg/ml cerium oxide nanocrystal and 12ml of N, N-dimethylformamide solution with amino modified mesoporous silicon dioxide nanoparticles of 5mg/ml at 40 ℃ for 8 hours to obtain the cerium oxide/iron oxide/mesoporous silicon nanocomposite.
Example 3
(1) Synthesis and ligand conversion of cerium oxide nanocrystals: adding 0.4g of cerium acetate hydrate and 2.8g of oleylamine into 15ml of dimethylbenzene, stirring for 3 hours at room temperature, and raising the temperature to 85 ℃ at a heating rate of 2 ℃ per minute; injecting 1ml of deionized water into an inert gas protection reaction system, aging for three hours, precipitating with acetone, and centrifuging to obtain the cerium oxide nanocrystal.
And sequentially adding 20mg of the synthesized cerium oxide nanocrystal, 0.5g of 2-bromoisobutyric acid and 0.05g of citric acid into a mixed solvent of 7.5ml of chloroform and 7.5ml of N, N-dimethylformamide, and stirring for 4 hours to obtain the cerium oxide nanocrystal.
(2) Synthesis and ligand conversion of iron oxide nanocrystals: 2g of iron oleate, 1.2g of oleic acid, 2.5g of oleyl alcohol were added to 10g of octadecene. The mixture was stirred at room temperature and heated to 250 ℃ at a rate of 10 ℃ per minute. Maintaining the temperature for 30 minutes, cooling to room temperature, precipitating with acetone, and centrifuging to obtain the iron oxide nanocrystal.
20mg of the iron oxide nanocrystal obtained by synthesis, 0.5g of 2-bromoisobutyric acid and 0.05g of citric acid were sequentially added to a mixed solvent of 7.5ml of chloroform and 7.5ml of N, N-dimethylformamide and stirred for 4 hours to obtain the iron oxide nanoparticle.
(3) Synthesizing amino modified mesoporous silicon nanoparticles: 2g of hexadecyltrimethylammonium chloride and 0.04g of triethanolamine are added into 20ml of deionized water, stirred and heated to 95 ℃, added with 1.4ml of tetraethoxysilane and 160 mu L of 3-aminopropyltriethoxysilane, stirred and reacted for 0.5 hour. The amino modified mesoporous silicon nano-particles can be obtained by centrifuging and washing away the template agent by 1 wt% of sodium chloride methanol solution.
(4) Synthesis of cerium oxide/iron oxide/mesoporous silicon nanocomposite: 4ml of N, N-dimethylformamide solution with ligand conversion concentration of 3mg/ml of cerium oxide nanocrystal, 5ml of N, N-dimethylformamide solution with ligand conversion concentration of 3mg/ml of cerium oxide nanocrystal and 10ml of N, N-dimethylformamide solution with 5mg/ml of amino-modified mesoporous silica nanoparticles react at 25 ℃ for 4 hours to obtain the cerium oxide/iron oxide/mesoporous silicon nanocomposite.
Application example: cerium oxide/ferric oxide/mesoporous silicon nano/methylene blue composite material applied to AD treatment
(1) Evaluation of in vitro biocompatibility
preparation of drugs at different concentrations: 50mg of the cerium oxide/iron oxide/mesoporous silicon nanocomposite prepared in example 1 was dispersed in 10ml of an aqueous solution containing 300mg of methylene blue (Tau protein aggregation inhibitor), and the mixture was stirred at room temperature for 24 hours, centrifuged, and washed to obtain a carrier of 0.36mg/mg of methylene blue. The resulting product was redispersed with different volumes of sterile PBS solution to give different concentrations of drug.
Selecting a human bone marrow neuroblastoma cell strain (SH-SY5Y) to examine the in vitro biocompatibility of the cerium oxide/ferric oxide/mesoporous silicon/methylene blue nano composite material with different concentrations.
The result of the CCK-8 cell activity quantitative analysis is shown in figure 5, the control group shows that the cell survival rate of groups with different drug concentrations is over 90% only by using cell culture solution for incubation, and the cerium oxide/ferric oxide/mesoporous silicon/methylene blue nano composite material has good in vitro biocompatibility.
(2) Inhibition of neuronal cell death
Preparation of drugs at different concentrations: 50mg of the cerium oxide/iron oxide/mesoporous silicon nanocomposite prepared in example 1 was dispersed in 10ml of an aqueous solution containing 300mg of methylene blue (Tau protein aggregation inhibitor), and the mixture was stirred at room temperature for 24 hours, centrifuged, and washed to obtain a carrier of 0.36mg/mg of methylene blue. The resulting product was redispersed with different volumes of sterile PBS solution to give different concentrations of drug.
Establishing a cell model: SH-SY5Y cells were previously incubated with Okadaic Acid (OA) for 12 hours.
Treatment groups: the cells pretreated with OA were administered with a cell culture solution containing cerium oxide/iron oxide/mesoporous silicon/methylene blue nanocomposites with different concentrations.
positive control group: OA pretreated cells were given fresh cell culture fluid.
Blank control group: normal cells were given fresh medium.
After 24 hours, the cell activity was quantified by CCK-8, and the results of the cerium oxide/iron oxide/mesoporous silicon/methylene blue nanocomposite for inhibiting OA-induced neuronal cell death are shown in fig. 6, where OA has a significant effect of promoting neuronal cell death with a cell activity of only 24%. After the cerium oxide/iron oxide/mesoporous silicon/methylene blue nanocomposite is given, nerve cell death is inhibited, and the cell activity exceeds 70%, so that the composite has the effect of inhibiting OA-induced nerve cell death.
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 (8)
1. A cerium oxide/ferric oxide/mesoporous silicon nano composite material is characterized in that a ligand-converted cerium oxide nanocrystal and a ligand-converted ferric oxide nanocrystal are respectively modified on the surfaces of amino-modified mesoporous silicon nano particles; the ligand conversion is carried out by utilizing 2-bromoisobutyric acid; the particle size of the ligand-converted cerium oxide nanocrystal is 1-10 nm; the particle size of the ligand-converted iron oxide nanocrystal is 1-10 nm; the particle size of the amino-modified mesoporous silicon nanoparticles is 5-500 nm.
2. A method for preparing the cerium oxide/iron oxide/mesoporous silicon nanocomposite material according to claim 1, comprising the steps of:
1) adding cerium acetate and oleylamine into dimethylbenzene for reaction to obtain cerium oxide nanocrystal; performing ligand conversion by using 2-bromoisobutyric acid to obtain ligand-converted cerium oxide nanocrystal; the particle size of the ligand-converted cerium oxide nanocrystal is 1-10 nm;
2) adding iron oleate, oleic acid and oleyl alcohol into octadecene for reaction to obtain iron oxide nanocrystal; performing ligand conversion by using 2-bromoisobutyric acid to obtain ligand-converted iron oxide nanocrystals; the particle size of the ligand-converted iron oxide nanocrystal is 1-10 nm;
3) dissolving hexadecyl trimethyl ammonium chloride and triethanolamine in water, reacting for 0.5-5 h at 90-100 ℃, and continuously adding tetraethoxysilane and 3-aminopropyl triethoxysilane for reacting for 0.5-5 h to obtain amino modified mesoporous silicon nanoparticles; the particle size of the amino-modified mesoporous silicon nanoparticles is 5-500 nm;
4) Adding the ligand-converted cerium oxide nanocrystal, the ligand-converted iron oxide nanocrystal and the amino-modified mesoporous silicon nanoparticles into N-N dimethylformamide, and reacting at 5-60 ℃ for 3-15 h to obtain the cerium oxide/iron oxide/mesoporous silicon nanocomposite.
3. the preparation method of the cerium oxide/iron oxide/mesoporous silicon nanocomposite material according to claim 2, wherein the mass ratio of cerium acetate to oleylamine in the step 1) is 1: 7-9.
4. The method for preparing cerium oxide/iron oxide/mesoporous silicon nanocomposite as claimed in claim 2, wherein the mass ratio of the ferric oleate, the oleic acid, the oleyl alcohol and the octadecene in the step 2) is 1: 0.15-0.6: 0.5-2: 2.5 to 10.
5. The method for preparing cerium oxide/iron oxide/mesoporous silicon nanocomposite as claimed in claim 2, wherein the dosage ratio of cetyltrimethylammonium chloride, triethanolamine, tetraethoxysilane and 3-aminopropyltriethoxysilane in step 3) is as follows: 1.5-2.5 g: 0.03-0.05 g: 1.4-1.6 ml: 0.14-0.16 ml.
6. The method for preparing the cerium oxide/iron oxide/mesoporous silicon nanocomposite material according to claim 2, wherein the mass ratio of the ligand-converted cerium oxide nanocrystal, the ligand-converted iron oxide nanocrystal and the amino-modified mesoporous silicon nanoparticle in the step 4) is 1-5: 1-5: 1 to 15.
7. use of the cerium oxide/iron oxide/mesoporous silicon nanocomposite material according to claim 1 for preparing an anti-alzheimer disease medicament.
8. The application of the cerium oxide/iron oxide/mesoporous silicon nanocomposite material in preparing medicines for resisting Alzheimer disease according to claim 7, wherein the medicines for resisting Alzheimer disease are medicines taking Tau protein as a target.
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