A mesoporous silica nanomaterial coated with cerium dioxide, and a preparation method and application thereof

Abstract

The application discloses a kind of cerium dioxide coated mesoporous silica nanomaterial and its preparation method and application, it is related to mesoporous material field.Preparation method includes that cerium dioxide nanoparticle, water and organic solvent are mixed and pH is adjusted, and cerium dioxide nanomaterial solution is prepared;Hexadecyltrimethylammonium bromide-containing organic solution is added dropwise into nanomaterial solution under ultrasonic condition, decane and mesitylene are added respectively under the condition of stirring, and hexadecyltrimethylammonium bromide is removed by extraction, and cerium dioxide coated mesoporous silica is obtained.This application prepares the nanomaterial of regular shape and larger pore size under the condition of room temperature and normal pressure, and the loading efficiency of drug is significantly improved, because quercetin contains a large number of hydroxyl groups, can form intermolecular hydrogen bond with the silicon hydroxyl group of mesoporous silica, realizes the synergistic effect of cerium dioxide and quercetin to realize antioxidant stress.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of mesoporous materials, in particular to a kind of mesoporous silica nanomaterials wrapped cerium dioxide and its preparation method and application. BACKGROUND

[0002] Mesoporous silica nanoparticles (MSN) have high specific surface area, high pore volume, adjustable pore channel, easy surface modification and stable chemical properties, and are an extremely potential drug carrier due to its good biocompatibility and degradability. Therefore, in recent years, how to modify and transform this type of nano-carrier to improve its drug loading efficiency and drug release efficiency has become a popular research direction.

[0003] At present, more mesoporous silica loaded quercetin is functionalized and modified on silica, and the experimental process is relatively complicated. At present, there are very few studies on mesoporous silica with large pore size loaded with quercetin wrapped cerium dioxide nanoparticles, and there are also few discussions on the influence of mesoporous silica with different pore sizes on drug loading efficiency. For general synthesis experiments of large-pore silica modified materials, the reaction process needs high-temperature calcination, and even some need to use more non-polar solvents, the operation conditions are harsh, and the subsequent treatment is relatively complex. SUMMARY

[0004] The present application provides a kind of mesoporous silica nanomaterials wrapped cerium dioxide and its preparation method and application, to improve the stability of nanomaterial and its drug loading efficiency of quercetin and other drugs.

[0005] To solve the above technical problems, one of the purposes of the present application provides a preparation method of mesoporous silica nanomaterials wrapped cerium dioxide, comprising the following steps:

[0006] (1) mix cerium dioxide nanoparticles, water and organic solvent, and adjust the pH value to 10 to prepare a cerium dioxide nanomaterial solution;

[0007] (2) add an organic solution containing cetyltrimethylammonium bromide to the nanomaterial solution under ultrasonic conditions, add decane under stirring conditions, stir for 30-90 min, then add mesitylene, stir for 1.5-2 h, then slowly add an organic solution containing tetraethyl orthosilicate under stirring conditions, and obtain a mixed solution after ultrasonic and stirring treatment;

[0008] (3) repeatedly wash and extract cetyltrimethylammonium bromide in the mixed solution with ammonium nitrate buffer solution, and obtain mesoporous silica wrapped cerium dioxide after centrifugal ultrasonic redispersion;

[0009] The mass ratio of the cetyltrimethylammonium bromide and decane in the mixed solution of step (2) is 1: (2-10); the mass ratio of the cetyltrimethylammonium bromide and mesitylene is 1: (1-3); the mass ratio of the cetyltrimethylammonium bromide and tetraethyl orthosilicate is 1: (3.5-4); the volume ratio of the organic solvent and water is (2-3): (7-8); and the mass ratio of the cerium dioxide nanomaterial and cetyltrimethylammonium bromide is (1-2): 3.

[0010] By using the above scheme, the cerium dioxide nanoparticles generally exhibit a high tendency to aggregate in a physiological medium, the novel nanoscale enzyme composite material of the CeO2 nanoscale enzyme embedded in the mesoporous silica shell has increased stability in a physiological medium compared to small-sized CeO2, and maximizes the ROS scavenging activity thereof and reduces the presence thereof in organs other than the liver, thereby improving the safety of CNPs. In the present application, under the conditions of room temperature and normal pressure, a drug-loaded system of macroporous mesoporous silica wrapping silica nanoparticles is prepared by using a mild experimental method. The mesoporous silica can not only protect the loaded drug or combined inorganic nanoparticles, but also has excellent catalytic activity by itself due to the presence of nanoscale enzymes and the like, and can achieve the effect of "1+1>2" by synergistic action with the loaded drug. By adjusting the amount of added decane and the stirring time, the degree of full entry of decane into the hydrophobic end of the cetyltrimethylammonium bromide micelle is changed, thereby controlling the degree of pore expansion of the particles. By controlling the amount of added mesitylene and the stirring time, the degree of cation-π interaction of mesitylene with the head group of cetyltrimethylammonium bromide and the diffusion degree between the alkyl chains of cetyltrimethylammonium bromide are controlled, which affects the nucleophilic substitution-polymerization reaction of the subsequently added tetraethyl orthosilicate, thereby controlling the reaction kinetics process through subtle adjustment and control, so as to control the final morphology and pore expansion degree of the silica nanoparticles, and obtain a nano material with regular shape and large pore size, which significantly improves the drug loading efficiency.

[0011] As a preferred scheme, in step (1), cerium nitrate hexahydrate and concentrated ammonia water are added to an aqueous solution at a final concentration of 9-11 mmol / L and 0.15-0.20 mol / L, respectively, stirred for 12-36 h, centrifuged to remove the supernatant, and then 0.05-0.06 mol / L ammonia water solution is added again for ultrasonic dispersion.

[0012] As a preferred solution, in step (2), the organic solution containing cetyltrimethylammonium bromide includes cetyltrimethylammonium bromide, water and organic solvent in a mass ratio of 3:(50-100):(10-30), the organic solution containing tetraethyl orthosilicate includes tetraethyl orthosilicate and organic solvent in a mass ratio of 1:(3-5), and the concentration of cerium dioxide nanoparticles in the mixed solution is 0.2-1 mg / mL. As a preferred solution, in steps (1) and (2), the organic solvent is ethanol.

[0013] As a preferred solution, in step (2), the organic solution containing tetraethyl orthosilicate is slowly added dropwise under stirring, and after ultrasonic treatment for 1-5 min, stirring is performed for 8-24 h.

[0014] As a preferred solution, the mesoporous silica encapsulating cerium dioxide has a pore size of 3.5-6.16 mm.

[0015] To solve the above technical problems, a second object of the present application provides a mesoporous silica encapsulating cerium dioxide obtained by the above preparation method.

[0016] To solve the above technical problems, a third object of the present application provides an application of the mesoporous silica encapsulating cerium dioxide in drug loading.

[0017] To solve the above technical problems, a fourth object of the present application provides a preparation method of quercetin-loaded mesoporous silica encapsulating cerium dioxide, which uses the above mesoporous silica encapsulating cerium dioxide and includes the following steps: dissolving quercetin and an organic solvent to obtain a solution with a solute concentration of 0.01-0.03 g / mL, centrifuging to remove the supernatant, and placing the solution in the dark overnight; mixing the supernatant with a solution of the mesoporous silica encapsulating cerium dioxide, so that the concentration of the mesoporous silica encapsulating cerium dioxide in the mixed solution is 7-8 mg / mL, stirring in the dark for 12-48 h, removing the supernatant by centrifugation, washing the precipitate with an organic solvent, and redispersing the nanoparticles with the organic solvent to obtain quercetin-loaded mesoporous silica encapsulating cerium dioxide.

[0018] By using the above solution, because quercetin contains a large number of hydroxyl groups, it can form intermolecular hydrogen bonds with the silicon hydroxyl groups of the mesoporous silica, so that the mesoporous silica encapsulating cerium dioxide nanoparticles load quercetin by the solvent impregnation method. The large pore size of the nanomaterials affects the in vivo release rate, and the small pore size affects the loading efficiency. By using a simple experimental procedure, the synergistic effect of cerium dioxide and quercetin on antioxidant stress is achieved, the antioxidant effect is improved, and the drug loading efficiency of mesoporous silica on quercetin is greatly improved.

[0019] In order to solve the above technical problems, the fifth object of the present application provides a quercetin-loaded mesoporous silica nanomaterial coated with cerium dioxide obtained by the above preparation method.

[0020] Compared with the prior art, the embodiments of the present application have the following beneficial effects:

[0021] 1. Cerium dioxide nanoparticles generally exhibit a high tendency to aggregate in physiological media. The novel nanenzyme composite material of the CeO2 nanenzyme embedded in the mesoporous silica shell has increased stability in physiological media compared to small-sized CeO2, maximizes their ROS scavenging activity, reduces their presence in organs other than the liver, and improves the safety of CNPs.

[0022] 2. The present application uses mild experimental methods to prepare a large-pore mesoporous silica drug-loaded system coated with silica nanoparticles at room temperature and normal pressure. The regular-shaped and large-pore nanomaterial significantly improves the drug loading efficiency. The mesoporous silica not only protects the loaded drugs or combined inorganic nanoparticles, but also has excellent catalytic activity itself due to the presence of nanenzymes, etc. Through synergistic action with the loaded drugs, the effect of "1+1>2" can be achieved.

[0023] 3. Quercetin contains a large number of hydroxyl groups, which can form intermolecular hydrogen bonds with the silicon hydroxyl groups of mesoporous silica. The nanomaterial prepared by the present application can improve the loading efficiency and release rate. Through simple experimental steps, the synergistic effect of cerium dioxide and quercetin against oxidative stress is achieved. The CeO2@mSiO2 nanomaterial after hole expansion has higher release efficiency than the conventional pore size CeO2@mSiO2 nanomaterial. BRIEF DESCRIPTION OF DRAWINGS

[0024] Figure 1 : is a schematic diagram of the atomic van der Waals radius simulation of quercetin of the present application;

[0025] Figure 2 : is the three-dimensional space coordinate data of quercetin atoms of the present application;

[0026] Figure 3 : is the DLS intensity number distribution graph of the nanomaterial in Examples 1-2 (Note: the upper graph a is the CeO2@mSiO2 of Example 1; the lower graph b is the CeO2@mSiO2 of Example 2);

[0027] Figure 4 : is the TEM graph of the nanomaterial in Examples 1-2 (Note: the upper graph a is the CeO2@mSiO2 of Example 1; the lower graph b is the CeO2@mSiO2 of Example 2);

[0028] Figure 5 : TEM image of the nanomaterial in Example 3 of this invention;

[0029] Figure 6 : TEM image of the nanomaterial in Example 4 of this invention;

[0030] Figure 7 : TEM image of the nanomaterial in Comparative Example 1 of this invention;

[0031] Figure 8 : TEM image of the nanomaterial in Comparative Example 2 of this invention;

[0032] Figure 9 : TEM image of the nanomaterial in Comparative Example 3 of this invention;

[0033] Figure 10 : TEM image of the nanomaterial in Comparative Example 4 of this invention;

[0034] Figure 11 : This is the high-angle annular dark field (HAADF) image and elemental mapping of the nanomaterial in Example 2 of this invention;

[0035] Figure 12 The figures above are the N2 adsorption-desorption isotherm curves (left) and DFT pore size distribution curves (right) of the nanomaterials in Examples 1-2 of this invention (Note: the upper left figure a is the N2 adsorption-desorption isotherm curve of CeO2@mSiO2 in Example 1; the upper right figure a is the DFT pore size distribution curve of CeO2@mSiO2 in Example 1; the lower left figure b is the N2 adsorption-desorption isotherm curve of CeO2@mSiO2 in Example 2; the lower right figure b is the DFT pore size distribution curve of CeO2@mSiO2 in Example 2).

[0036] Figure 13 : The UV absorption spectra of the quercetin-loaded nanomaterial solution in Examples 1-2 of this invention after 5 min and 24 h (Note: 1 is the UV absorption spectrum of CeO2@mSiO2 loaded with quercetin in Example 1 (pore size D)). v =3 nm); 2 is an application example 2 of loading quercetin CeO2@mSiO2 (pore size D v =6 nm). Detailed Implementation

[0037] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0038] Preparation Example One

[0039] A method for preparing CeO2NPs, comprising the following steps:

[0040] Cerium nitrate hexahydrate (Ce(NOs)2. 4H2O) and concentrated ammonia (NH3. H2O) were added to an aqueous solution at a final concentration of 10 mmol / L and 0.2 mol / L, respectively, to a final volume of 50 mL, mixed, and the mixture was mixed overnight under stirring to form CeO2NPs at a concentration of 1.72 mg / mL.

[0041] Example One

[0042] A method for preparing CeO2@mSiO2 (pore size D v = 3 nm) nanomaterials, comprising the following steps:

[0043] a. Prepare a CTAB solution: cetyltrimethylammonium bromide (CTAB) was added to a 5 mL centrifuge tube, mixed and dissolved with H2O and anhydrous ethanol (EtOH), and the mass ratio of cetyltrimethylammonium bromide, water, and anhydrous ethanol was 3:80:16;

[0044] b. Prepare a nanomaterial solution: the CeO2NPs solution obtained in Preparation Example One was taken in a reagent bottle, H2O and anhydrous ethanol were added, and the pH was adjusted to 10 with concentrated ammonia (30 wt%), and mixed and ultrasonicated for 15 min;

[0045] c. Under ultrasonic conditions, the CTAB solution was added dropwise into the nanomaterial solution, and the mixture was ultrasonicated for 30 min after shaking;

[0046] d. Under stirring conditions, an ethanol solution containing tetraethyl orthosilicate (TEOS) was slowly added dropwise, the mixture was ultrasonicated for 2 min after mixing, and then stirred for 24 h, and the organic solution containing tetraethyl orthosilicate (TEOS) included tetraethyl orthosilicate and anhydrous ethanol at a volume ratio of 1:5;

[0047] At this time, the total parameter ratio in the solution system was: CeO2NPs : CTAB = 1.2:3 (w / w), EtOH : H2O = 1:4 (v / v), n(TEOS) / n(CTAB) = 3.3, and the concentration of CeO2NPs was 0.5 mg / mL;

[0048] e. The CTAB in the solution was removed by adding 40 mL of NH4NO3 buffer and repeating centrifugation (12 min, RCF 15000, 12°C) and ultrasonic dispersion three times;

[0049] f. The nanoparticles were redispersed with ethanol.

[0050] Example Two

[0051] A method for preparing CeO2@mSiO2 (pore size D v =6 nm) nanomaterials, comprising the following steps:

[0052] a. Preparation of CTAB solution: weigh cetyltrimethylammonium bromide (CTAB) in a 5 mL centrifuge tube, add H2O and anhydrous ethanol (EtOH), and dissolve by rotating in a rotating mixer for 30 min. The mass ratio of cetyltrimethylammonium bromide, water and anhydrous ethanol is 3:80:16;

[0053] b. Preparation of nanomaterial solution: take the CeO2 NPs solution obtained in Preparation Example 1 in a reagent bottle, add water and anhydrous ethanol, and adjust the pH to 10 with concentrated ammonia water (30 wt%), and mix and ultrasonic for 15 min;

[0054] c. Under ultrasonic conditions, drop the CTAB solution into the nanomaterial solution, shake evenly while dropping, and ultrasonic for 30 min after mixing;

[0055] d. Under stirring conditions, add 330 μL of decane, and stir for 90 min;

[0056] e. Add 46 μL of mesitylene, and stir for 2 h;

[0057] f. Under stirring conditions, slowly add an ethanol solution containing tetraethyl orthosilicate (TEOS), ultrasonic for 2 min after mixing, and then stir for 24 h. The organic solution containing tetraethyl orthosilicate (TEOS) includes tetraethyl orthosilicate and anhydrous ethanol in a volume ratio of 7:30;

[0058] At this time, the total parameter ratio in the mixed solution system is: CeO2 NPs : CTAB = 1.2:3 (w / w), EtOH : H2O = 2.2:7.8 (v / v), n(Decane) / n(CTAB)=10, n(Mesitylen) / n(CTAB)=2, n(TEOS) / n(CTAB)=3.85, and the concentration of CeO2 NPs is 0.5 mg / mL;

[0059] g. Remove the CTAB in the solution by ultrasonic dispersion by adding 40 mL of NH4NO3 buffer and repeating centrifugation (12 min, RCF 15000, 12°C) 3 times;

[0060] h. Redisperse the nanoparticles with ethanol.

[0061] Example Three

[0062] A method for preparing CeO2@mSiO2 nanomaterials, each step and the reagents and process parameters used in each step are the same as in Example Two, the difference is that in the mixed system of step f: EtOH:H2O (v / v) = 2.2:7.8, n(Decane) / n(CTAB)=10, n(Mesitylen) / n(CTAB)=2, n(TEOS) / n(CTAB)=3.6.

[0063] Example Four

[0064] A method for preparing CeO2@mSiO2 nanomaterials, each step and the reagents and process parameters used in each step are the same as in Example Two, the difference is that in the mixed system of step f: EtOH:H2O (v / v) = 2.2:7.8, n(Decane) / n(CTAB)=10, n(Mesitylen) / n(CTAB)=2, n(TEOS) / n(CTAB)=4.

[0065] Comparative Example One

[0066] A method for preparing CeO2@mSiO2 nanomaterials, each step and the reagents and process parameters used in each step are the same as in Example Two, the difference is that in the mixed system of step f: EtOH:H2O (v / v) = 1:4, n(Decane) / n(CTAB)=10, n(Mesitylen) / n(CTAB)=3.5, n(TEOS) / n(CTAB)=3.3.

[0067] Comparative Example Two

[0068] A method for preparing CeO2@mSiO2 nanomaterials, each step and the reagents and process parameters used in each step are the same as in Example Two, the difference is that in the mixed system of step f: EtOH:H2O (v / v) = 1:4, n(Decane) / n(CTAB)=10, n(Mesitylen) / n(CTAB)=2, n(TEOS) / n(CTAB)=3.3.

[0069] Comparative Example Three

[0070] A method for preparing CeO2@mSiO2 nanomaterials, each step and the reagents and process parameters used in each step are the same as in Example Two, the difference is that in the mixed system of step f: EtOH:H2O (v / v) = 1:4, n(Decane) / n(CTAB)=10, n(Mesitylen) / n(CTAB)=2, n(TEOS) / n(CTAB)=4.3.

[0071] Comparative Example 4

[0072] A method for preparing CeO2@mSiO2 nanomaterials is provided. The steps, reagents, and process parameters used in each step are the same as those in Example 2. The difference is that in the mixing system of step f: EtOH:H2O (v / v) = 2.2:7.8, n(Decane) / n(CTAB) = 10, n(Mesitylen) / n(CTAB) = 2, and n(TEOS) / n(CTAB) = 3.3.

[0073] Application Example 1

[0074] A CeO2@mSiO2 loaded with quercetin (pore size D) v =3 nm) nanomaterials, including the following preparation steps:

[0075] (1) Before filling quercetin, a three-dimensional spatial model of quercetin was constructed using Chem3D. When calculating the size of quercetin, van der Waals radius was selected. The set of data used for this purpose was given by Pauling, refined by Bondi, and corrected by Gavezotti, Rowland and Taylor et al. Mantina et al. obtained a set of self-consistent radius data containing all main group elements using quantization methods. The reference paper is as follows: Manjeera Mantina, Adam C. Chamberlin, Rosendo Valero, Christopher J. Cramer, Donald G. Truhlar; Consistent van der Waals Radii for the Whole Main Group; J. Phys. Chem. A 113(19):5806-5812, 2009; 10.1021 / jp8111556. In this embodiment, the radius of quercetin is close to 1.3 nm.

[0076] (2) Preparation of quercetin concentration correction curve in ethanol: 2 mg / mL quercetin solution was prepared with anhydrous ethanol, and 25 μL, 50 μL, 75 μL, 100 μL, 125 μL, 150 μL of the solution was diluted to 1 mL, respectively, to prepare solutions with concentrations of 0.05 mg / mL, 0.1 mg / mL, 0.15 mg / mL, 0.2 mg / mL, 0.25 mg / mL, and 0.3 mg / mL. Then, the solutions were diluted by 40 times to obtain solutions with concentrations of 0.0025 mg / mL, 0.005 mg / mL, 0.0075 mg / mL, 0.01 mg / mL, 0.0125 mg / mL, and 0.015 mg / mL. The standard concentration correction curve of quercetin was measured by a UV spectrophotometer as A = 84.32C - 0.020 (R2= 0.998) (A is the absorbance value, and C is the concentration mg / mL);

[0077] (3) Preparation of quercetin saturated ethanol solution: 200 mg of quercetin was dissolved in 10 mL of ethanol solution, centrifuged (15 min, RCF 20000, 24°C), and the supernatant was taken out and placed in the dark overnight. 6 mL of the supernatant was mixed with the nanomaterial solution obtained in Example 1, and the concentration of the nanomaterial after mixing was 7 mg / mL. The mixture was stirred in the dark for 24 hours, 1 mL of the solution was taken out and centrifuged (12 min, RCF 20000, 12°C), the supernatant was removed, the precipitate was washed twice with 1 mL of anhydrous ethanol, and the nanomaterial was redispersed in 1 mL of anhydrous ethanol. The absorbance value of the loaded quercetin in the nanomaterial was measured by a UV spectrophotometer, and the concentration correction curve was used to calculate the absorbance value.

[0078] Application Example Two

[0079] A quercetin-loaded CeO2@mSiO2 (pore size D v = 6 nm) nanomaterial, comprising the following preparation steps:

[0080] (1) Before loading quercetin, use Chem3D to construct a three-dimensional spatial model of quercetin. When calculating the size of quercetin, select the van der Waals radius. A set of data is given by Pauling, refined by Bondi, and corrected by Gavezotti, Rowland and Taylor. Mantina et al. obtained a set of self-consistent radius data for all main group elements using a quantitative method. The reference paper is as follows: Manjeera Mantina, Adam C. Chamberlin, Rosendo Valero, Christopher J. Cramer, Donald G. Truhlar; Consistent van der Waals Radii for the Whole Main Group; J. Phys. Chem. A 113(19):5806-5812, 2009; 10.1021 / jp8111556. The radius of quercetin in this embodiment is close to 1.3 nm;

[0081] (2) Prepare the concentration correction curve of quercetin in ethanol: prepare a 2 mg / mL quercetin solution with anhydrous ethanol, and dilute 25 μL, 50 μL, 75 μL, 100 μL, 125 μL, 150 μL of the solution to 1 mL to prepare solutions with concentrations of 0.05 mg / mL, 0.1 mg / mL, 0.15 mg / mL, 0.2 mg / mL, 0.25 mg / mL, and 0.3 mg / mL. Dilute again by 40 times to obtain solutions with concentrations of 0.0025 mg / mL, 0.005 mg / mL, 0.0075 mg / mL, 0.01 mg / mL, 0.0125 mg / mL, and 0.015 mg / mL. The standard concentration correction curve of quercetin measured by the ultraviolet spectrophotometer is A=84.32C-0.020 (R2=0.998) (A is the absorbance, and C is the concentration mg / mL);

[0082] (3) Preparation of a saturated ethanol solution of quercetin: 200 mg of quercetin was dissolved in 10 mL of an ethanol solution, centrifuged (15 min, RCF 20000, 24°C), and the supernatant was removed and left to stand in the dark overnight. 6 mL of the supernatant was mixed with the nanomaterial solution obtained in Example 2, and the solubility of the nanomaterial after mixing was 7 mg / mL. The mixture was stirred in the dark for 24 hours, 1 mL of the solution was removed and centrifuged (12 min, RCF 20000, 12°C), the supernatant was removed, the precipitate was washed twice with 1 mL of anhydrous ethanol, and the nanomaterial was redispersed in 1 mL of anhydrous ethanol. The absorbance of the quercetin loaded in the nanomaterial was measured again using a UV spectrophotometer, and the absorbance was calculated by substituting the concentration correction curve.

[0083] Performance detection test

[0084] As shown in Figure 3 , the nanomaterials of Example 1-2 were detected by dynamic light scattering instrument DLS to obtain the hydrodynamic diameter of the nanomaterials and thus obtain the particle size information of the samples. As shown in Figure 3 , the pore diameter D v = 3 nm of the nanomaterials was not much different from the pore diameter D v = 6 nm of the nanomaterials in terms of nanomaterial diameter, i.e. when the pore diameter of the nanomaterials was expanded, the size of the nanomaterials did not increase significantly.

[0085] As shown in Figures 4-10 , the TEM images of the nanomaterials of Example 1-4 and Comparative Example 1-4 were obtained by FEI Tecnai F20 transmission electron microscope, and the results are shown in Figures 4-10 . As shown in Figure 4 , the pore diameter D v = 6 nm of the nanomaterials of Example 2 was significantly larger than the pore diameter D v = 3 nm of the nanomaterials of Example 1, and the shape was regular, CeO2 was wrapped in mesoporous SiO2, and the degree of order of the pore diameter was high. As shown in Figures 5-6 , the nanomaterials of Example 3-4 were successfully synthesized after adjusting the content of tetraethyl orthosilicate, but the particle size of the nanomaterials was not as uniform as that of Example 2. As shown in Figures 7-10 , the nanomaterials synthesized in Comparative Example 1-4 were not complete in shape and had a low degree of order of the pores.

[0086] As shown in Figure 11As shown in the HAADF image of the nanomaterial of Example 2 obtained by a high-angle annular dark field scanning transmission electron microscope, the dark field image formed by high-angle diffraction spots can measure the composition, and the shape and element distribution of the material can be seen. The CeO2 NPs are distinguished as a brighter part in the HAADF image, and the rest is Si and O elements, and compared with the TEM image, the nanomaterial CeO2@mSiO2 is overlapped in the element mapping of O, Si and Ce in the HAADF image, and according to the distribution position, it can be seen that the nanometer CeO2 NPs are wrapped in the mesoporous silica.

[0087] As shown in Figure 12 , the nitrogen adsorption-desorption measurement is obtained by using a full-automatic specific surface and porosity analyzer (Quantachrome Autosorb IQ3), the nanomaterial samples of Examples 1-2 are vacuum degassed at 300°C for 8 h, and the pore size distribution of the samples is evaluated by using the DFT method. As can be seen from the figure, the pore size distribution of the CeO2@mSiO2 of Example 1 is about 3 nm, while the pore size distribution of the CeO2@mSiO2 of Example 2 is about 6 nm, which indicates that the pore expansion is successful.

[0088] As shown in Figure 13 , the absorbance value at 373 nm of the quercetin-loaded nanomaterial solution of Application Examples 1-2 after 5 min and 24 h is detected by a UV spectrophotometer, and as can be seen from the figure, the drug loading amount of the nanomaterial of Example 2 in Application Example 2 is more than that of the nanomaterial of Example 1 in Application Example 1, and by calculating the drug loading amount of CeO2@mSiO2 (pore size D v =3 nm) is 0.27 mg / mL, and the drug loading amount of CeO2@mSiO2 (pore size D v =6 nm) is 0.36 mg / mL, and the drug loading efficiency can be increased by 33%.

[0089] The above specific embodiments further illustrate the purpose, technical solutions and beneficial effects of the present application, and it should be understood that the above description is only for specific embodiments of the present application and does not limit the protection scope of the present application. It is particularly pointed out that any modification, equivalent replacement, improvement, etc. made by those skilled in the art within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. A method for preparing quercetin-loaded mesoporous silica nanomaterials coated with cerium dioxide, characterized by, The preparation method of the mesoporous silica nanomaterials wrapped with cerium dioxide comprises the following steps: The preparation method of the mesoporous silica nanomaterials wrapped with cerium dioxide comprises the following steps: (1) mixing cerium dioxide nanoparticles, water and an organic solvent, and adjusting the pH value to 9-10 to prepare a cerium dioxide nanomaterial solution; (2) adding an organic solution containing cetyltrimethylammonium bromide into the nanomaterial solution under ultrasonic condition, adding decane under stirring condition, stirring for 30-90 min, then adding mesitylene, stirring for 1.5-2 h, then slowly adding an organic solution containing tetraethyl orthosilicate under stirring condition, and treating by ultrasonic and stirring to obtain a mixed solution; In steps (1) and (2), the organic solvent is ethanol; In the mixed solution of step (2), the mass ratio of the cetyltrimethylammonium bromide to the decane is 1:10; the mass ratio of the cetyltrimethylammonium bromide to the mesitylene is 1:2; the mass ratio of the cetyltrimethylammonium bromide to the tetraethyl orthosilicate is 1:(3.6-4); the volume ratio of the organic solvent to water is 2.2:7.8; and the mass ratio of the cerium dioxide nanomaterial to the cetyltrimethylammonium bromide is 1.2:3; In step (2), the organic solution containing cetyltrimethylammonium bromide comprises cetyltrimethylammonium bromide, water and an organic solvent with a mass ratio of 3:80:16, and the organic solution containing tetraethyl orthosilicate comprises tetraethyl orthosilicate and an organic solvent with a mass ratio of 7:30, and the concentration of cerium dioxide nanoparticles in the mixed solution is 0.5 mg / mL. In step (1), the preparation method of the cerium dioxide nanoparticles is as follows: adding cerium nitrate hexahydrate and concentrated ammonia water into an aqueous solution with final concentrations of 9-11 mmol / L and 0.15-0.20 mol / L, respectively, stirring for 12-36 h, removing the supernatant by centrifugation, adding a 0.05-0.06 mol / L ammonia water solution to re-disperse ultrasonically, and obtaining a cerium dioxide nanoparticle solution with a cerium dioxide nanoparticle concentration of 1-3 mg / mL.

2. The method for preparing quercetin-loaded, cerium-encapsulated mesoporous silica nanomaterials as described in claim 1, characterized in that, In step (2), the organic solution containing tetraethyl orthosilicate is slowly added dropwise under stirring condition, ultrasonic treatment is performed for 1-5 min, and then stirring is performed for 8 h-24 h.

3. The method of claim 1, wherein the quercetin-loaded, ceria-coated mesoporous silica nanomaterial is prepared by the following steps: (1) preparing a quercetin-loaded mesoporous silica nanomaterial; (2) preparing a ceria-coated mesoporous silica nanomaterial; and (3) mixing the quercetin-loaded mesoporous silica nanomaterial and the ceria-coated mesoporous silica nanomaterial. ​ 4. The method of claim 1, wherein the quercetin-loaded, ceria-coated mesoporous silica nanomaterial is prepared by the following steps: (1) preparing a quercetin-loaded mesoporous silica nanomaterial; (2) preparing a ceria-coated mesoporous silica nanomaterial; and (3) mixing the quercetin-loaded mesoporous silica nanomaterial and the ceria-coated mesoporous silica nanomaterial. The mesoporous silica encapsulating ceria has a pore size of about 6 nm.

5. A quercetin-loaded mesoporous silica encapsulating ceria nanomaterial obtained by the preparation method according to any one of claims 1-4.

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