Preparation method of degradable functionalized silicon-based bioactive nano platform

Abstract

The invention aims to provide a preparation method of a degradable functionalized silicon-based bioactive nano platform, which belongs to the technical field of nano materials, and comprises the following steps: dripping an oil-phase solution containing a silicon source into a water-phase solution containing a manganese source by using an oil-water two-phase method; mesoporous Mn / Si nanoparticles uniformly doped with manganese can be obtained through stirring under a mild heating condition and high-temperature calcination, and drug loading and bovine serum albumin coating are further realized through stirring. The preparation method is simple in synthesis step, short in time consumption, uniform in metal doping, stable in product structure and good in drug loading capacity. The degradation performance of the nano-platform can be regulated and controlled by regulating and changing the adding amount of the swelling agent, the surfactant and the manganese source in the synthesis system. The diameter of the prepared degradable functionalized silicon-based bioactive nano platform is 115-145 nm, and the degradable functionalized silicon-based bioactive nano platform can be responsively degraded in an acidic microenvironment to release ions and drugs and is expected to be used for diagnosis and treatment of diseases.

Description

Technical Field

[0001] This invention belongs to the field of nanomaterials technology, specifically relating to a method for preparing a biodegradable functionalized silicon-based bioactive nanoplatform. Background Technology

[0002] In recent years, inorganic nanomaterials have attracted widespread attention due to their excellent biocompatibility, low immunogenicity, controllable structure, and high stability. Among them, mesoporous silica nanoparticles, with their high specific surface area, abundant pore structure, adjustable pore size, ease of surface modification, good biocompatibility, and high chemical and thermal stability, can be widely used as drug carriers to improve drug stability and solubility, and enhance drug bioavailability and delivery efficiency. However, traditional mesoporous silica nanoparticles, due to their highly stable Si-O-Si framework structure, are difficult to degrade under physiological or pathological conditions, and these nanoparticles are prone to accumulate in vital organs, leading to serious side effects. There is an urgent need to develop a silicon-based nanoplatform that can degrade in response to the microenvironment to improve the precise delivery and controlled release of drugs.

[0003] Based on this, metal-doped mesoporous silica nanoparticles have emerged. By introducing a metal species M into the silica framework, on the one hand, due to the change in framework structure, the bond energy of the formed -MO-Si- bonds is much lower than that of the -Si-O-Si- bonds, making the nanoparticles extremely unstable in acidic environments and easily oxidized by H. + The attack caused the nanoparticles to undergo responsive degradation, and the breaking of the -MO-Si bonds led to defects in the framework structure, further accelerating the degradation. This characteristic is beneficial for the controlled release of drugs when loaded onto the nanoparticles, improving drug delivery efficiency and bioavailability. On the other hand, the introduction of metal species can also enable the nanoparticles to exhibit the properties of the metal species themselves, enriching their functionality, broadening their application fields, and providing a platform for the development of novel nanomaterials. Currently, common methods for synthesizing metal-doped mesoporous silica nanoparticles mainly include sol-gel methods, hydrothermal methods, impregnation methods, and ion exchange / adsorption equilibrium methods. Although these methods can introduce metals, they often face problems such as cumbersome synthesis steps, poor doping uniformity, easy collapse of pore structures, and low doping levels. Therefore, a preparation process that combines simple synthesis steps, uniform doping, and controllable product structure is needed. Summary of the Invention

[0004] The purpose of this invention is to provide a method for preparing a biodegradable functionalized silicon-based bioactive nanoplatform. This method has simple synthesis steps, and the synthesized nanoplatform can undergo responsive degradation in an acidic microenvironment to release loaded drugs and metal ions, which is expected to be used for the diagnosis and treatment of diseases.

[0005] The present invention adopts the following technical solution: A method for preparing a biodegradable functionalized silicon-based bioactive nanoplatform includes the following steps: S1. Mix the swelling agent and silicon source in a certain proportion, and stir at 880 r / min for 20 min to obtain a colorless and transparent homogeneous liquid system, i.e., an oil phase solution. S2. Mix the structure-directing agent, catalyst and deionized water in a certain proportion, and stir at 880 r / min for 15-30 min at room temperature to form a homogeneous and transparent solution. S3. Weigh out the inorganic manganese source and dissolve it in deionized water. Sonicate the solution at 60 kHz for 5 min to form a uniformly dispersed manganese source solution. Then add the solution to S2 dropwise at a rate of 3 s / drop. Stir the solution at 880 r / min for 15 min at room temperature to obtain a uniformly dispersed aqueous solution. S4. The oil phase solution prepared in S1 is added dropwise to the aqueous phase solution in S3 at a rate of 3s / drop. The solution is stirred at 880r / min for 12h at 60℃. The solution gradually changes from the initial colorless and transparent state to milky white. S5. The milky white mixture obtained in S4 is centrifuged at a speed of 8000 r / min for 15 min to achieve solid-liquid separation. The precipitate is collected, washed with water 3-5 times and purified by centrifugation to finally obtain a white solid product. S6. Dry, grind and calcine the white solid product obtained in S5 to obtain mesoporous Mn / Si nanoparticles. S7. Dissolve the mesoporous Mn / Si nanoparticles obtained in S6 in deionized water, and disperse them into a uniform aqueous solution after ultrasonic treatment. The concentration of the aqueous solution is 20 mg / mL, the volume is 1 mL, the ultrasonic frequency is 60 kHz, and the ultrasonic time is 5 min. S8. Weigh abexicillin powder and dissolve it in dimethyl sulfoxide solution. After ultrasonic dispersion and dissolution to form a colorless and transparent abexicillin solution, slowly add it dropwise to the aqueous solution in S7. Stir rapidly at room temperature to obtain a mixed solution. The ultrasonic frequency is 60 kHz, the ultrasonic treatment time is 5 min, the dropping rate is 3 s / drop, the stirring speed at room temperature is 880 r / min, and the stirring time is 12-24 h. S9. The mixed solution obtained in S8 is purified by multiple high-speed centrifugations and water washing to obtain Mn / Si-Abe nanoparticles; the high-speed centrifugation speed is 8000 r / min, the centrifugation time is 20 min, and the number of washing times is 3-5. S10. Weigh bovine serum albumin and add it to deionized water. Stir at 880 r / min for 15 min at room temperature until fully dissolved. Then, sonicate at 80 kHz for 15 min to form a transparent, pale yellow bovine serum albumin aqueous solution. Dissolve the Mn / Si-Abe nanoparticles obtained in S9 in deionized water and sonicate at 80 kHz for 5 min to form a uniform Mn / Si-Abe nanoparticle aqueous solution. Then, add the Mn / Si-Abe nanoparticles dropwise to the bovine serum albumin aqueous solution at a rate of 3 s / drop. Stir at 880 r / min for 12-24 h at room temperature to obtain a mixed solution. S11. The mixed solution obtained in S10 is subjected to multiple high-speed centrifugation and water washing purification to remove excess bovine serum albumin, thereby obtaining the degradable functionalized silicon-based bioactive nanoplatform Mn / Si-Abe@BSA; the high-speed centrifugation speed is 8000 r / min, the centrifugation time is 10 min, and the number of washing times is 3-5.

[0006] Further, in S1, the swelling agent is chlorobenzene, and the silicon source is tetraethyl orthosilicate; the ratio of the swelling agent to the silicon source is 3.5-3.85 mL: 0.55 mL.

[0007] Further, in S2, the structure directing agent is a 25wt% aqueous solution of hexadecyltrimethylammonium chloride, and the catalyst is triethanolamine; the ratio of the structure directing agent, catalyst, and deionized water is 4.8-5mL: 0.04-0.045g: 7-7.2mL.

[0008] Furthermore, in S3, the inorganic manganese source is manganese chloride tetrahydrate, the concentration of the manganese source solution is 1 mM, and the amount used is 0.00-0.11 mL.

[0009] Furthermore, in S6, the drying step is carried out in a constant temperature forced-air drying oven at a drying temperature of 80°C for 12 hours; the high-temperature calcination step is carried out in a muffle furnace using a gradient calcination method: first, heat treatment is performed at 200°C for 1 hour, followed by heating to 550°C for another 2 hours.

[0010] Furthermore, in S8, the concentration of the abecitabine solution is 8.296 mM and the volume is 0.12-0.2 mL.

[0011] Further, in S10, the concentration of the bovine serum albumin aqueous solution is 20 mg / mL and the volume is 2.5-3 mL; the concentration of the Mn / Si-Abe nanoparticle aqueous solution is 5 mg / mL and the volume is 1 mL.

[0012] The nanoplatform has a sea urchin-like structure with a diameter of 115-145 nm, and undergoes responsive degradation in an acidic microenvironment to release ions and drugs.

[0013] The beneficial effects of this invention are as follows: This invention provides a method for preparing a biodegradable functionalized silicon-based bioactive nanoplatform. The synthesis steps are simple, the product structure is controllable, and it can undergo responsive degradation in an acidic microenvironment. By adjusting the amount of swelling agent, surfactant, and manganese source added to the synthesis system, the degradation performance of the nanoplatform can be regulated. Attached Figure Description

[0014] Figure 1 This is a transmission electron microscope image of the biodegradable functionalized silicon-based bioactive nanoplatform synthesized in Example 1 of the present invention.

[0015] Figure 2 The image shows the XRD pattern of the biodegradable functionalized silicon-based bioactive nanoplatform synthesized in Example 1 of this invention.

[0016] Figure 3 The nitrogen adsorption-desorption spectrum and pore size distribution of the biodegradable functionalized silicon-based bioactive nanoplatform synthesized in Example 1 of this invention are shown.

[0017] Figure 4 The image shows the XPS spectrum of Mn in the biodegradable functionalized silicon-based bioactive nanoplatform synthesized in Example 1 of this invention.

[0018] Figure 5 The image shows the UV-Vis absorption spectrum of the biodegradable functionalized silicon-based bioactive nanoplatform synthesized in Example 1 of this invention.

[0019] Figure 6 The image shows the zeta potential and particle size distribution of the biodegradable functionalized silicon-based bioactive nanoplatform synthesized in Example 1 of this invention.

[0020] Figure 7 Transmission electron microscope images of the biodegradable functionalized silicon-based bioactive nanoplatform synthesized in Example 1 of this invention undergoing biodegradation under different pH conditions.

[0021] Figure 8 The biodegradable functionalized silicon-based bioactive nanoplatform synthesized in Example 1 of this invention releases Mn in different pH media. 2+ The graph shows the cumulative release rate in vitro over time.

[0022] Figure 9 This is a graph showing the in vitro cumulative release rate of Abe over time in different pH release media of the biodegradable functionalized silicon-based bioactive nanoplatform synthesized in Example 1 of this invention. Detailed Implementation

[0023] 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.

[0024] Example 1 Preparation of a biodegradable functionalized silicon-based bioactive nanoplatform: S1. Preparation of oil phase solution: Mix 3.5 mL of chlorobenzene and 0.55 mL of tetraethyl orthosilicate in a glass container and stir magnetically at 880 r / min for 20 min to obtain a colorless and transparent homogeneous liquid system. S2. Preparation of aqueous solution: 4.8 mL of 25 wt% hexadecyltrimethylammonium chloride aqueous solution, 0.04 g of triethanolamine and 7.0 mL of deionized water are rapidly stirred at 880 r / min at room temperature for 15 min to form a homogeneous and transparent solution. S3. Weigh a certain amount of manganese chloride tetrahydrate and dissolve it in deionized water to form a 1mM solution. Sonicate the solution in an ultrasonic disperser at a frequency of 60kHz for 5 minutes to fully dissolve it into a colorless and transparent manganese chloride solution. Then, take 0.1mL of the manganese chloride solution and slowly add it dropwise to the solution in S2 at a rate of 3s / drop. Stir the mixture rapidly at 880r / min for 15 minutes at room temperature to obtain a uniformly dispersed aqueous solution. S4. The oil phase solution prepared in S1 is added dropwise to the aqueous phase solution in S3 at a rate of 3s / drop. The solution is stirred continuously at 880r / min for 12h at 60℃. The solution gradually changes from the initial colorless and transparent state to milky white. S5. The milky white mixture obtained in S4 is centrifuged at 8000 r / min for 15 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed three times with deionized water and purified by centrifugation under the same time and speed conditions to finally obtain a white solid product. S6. The white solid product obtained in S5 is dried at 80°C for 12 hours in a constant temperature drying oven and then ground into white powder by mortar and pestle. After that, it is calcined at 200°C for 1 hour in a muffle furnace, and then heated to 550°C and calcined for another 2 hours to obtain sea urchin-like mesoporous Mn / Si nanoparticles. S7. Dissolve the Mn / Si powder obtained in S6 in deionized water to prepare a solution of 20 mg / mL, and sonicate it at a frequency of 60 kHz for 5 min to disperse it into a uniform aqueous solution. S8. Weigh a certain amount of abexicillin powder and dissolve it in dimethyl sulfoxide to prepare an 8.296 mM solution. Sonicate the solution in an ultrasonic disperser at a frequency of 60 kHz for 5 min to fully dissolve it and form a colorless and transparent solution. Then, take 0.12 mL of the solution and slowly add it dropwise to 1 mL of the aqueous solution of S7 at a rate of 3 s / drop. Stir rapidly at a speed of 880 r / min for 12 h at room temperature. S9. The mixed solution obtained in S8 is centrifuged at 8000 r / min for 20 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed three times with deionized water and purified by centrifugation under the same time and speed conditions to obtain Mn / Si-Abe nanoparticles. S10. Weigh a certain amount of bovine serum albumin and add it to deionized water to prepare a 20 mg / mL solution. Stir at 880 r / min for 15 min at room temperature to ensure complete dissolution. Then, place it in an ultrasonic disperser and sonicate at 80 kHz for 15 min to obtain a uniformly dispersed, transparent, pale yellow solution. Dissolve the Mn / Si-Abe nanoparticles obtained in S9 in deionized water to prepare a 5 mg / mL solution. Sonicate at 80 kHz for 5 min to ensure uniform dispersion. Take 1 mL of this solution and add it dropwise to 2.5 mL of the above aqueous solution at a rate of 3 s / drop. Stir rapidly at 880 r / min for 12 h at room temperature. S11. The mixed solution obtained in S8 is centrifuged at 8000 r / min for 10 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed three times with deionized water and centrifuged under the same time and speed conditions to remove excess bovine serum albumin, thus obtaining the degradable functionalized silicon-based bioactive nanoplatform Mn / Si-Abe@BSA.

[0025] Figure 1 This is a transmission electron microscope image of the biodegradable functionalized silicon-based bioactive nanoplatform synthesized in Example 1. As can be seen from the image, the synthesized nanoplatform has a sea urchin-like structure with a particle size of approximately 115-145 nm.

[0026] Figure 2 The image shows the XRD pattern of the biodegradable functionalized silicon-based bioactive nanoplatform synthesized in Example 1. As can be seen from the image, the synthesized nanoplatform exhibits an amorphous, non-crystalline structure.

[0027] Figure 3 The figures show the nitrogen adsorption-desorption spectrum and pore size distribution of the biodegradable functionalized silicon-based bioactive nanoplatform synthesized in Example 1. As can be seen from the figures, the nitrogen adsorption-desorption curves of the synthesized nanoplatform are typical type IV isotherms, with an average pore size of 10.05 nm.

[0028] Figure 4 The figure shows the XPS spectrum of Mn in the biodegradable functionalized silicon-based bioactive nanoplatform synthesized in Example 1. As can be seen from the figure, the XPS spectrum of the Mn 2p orbital of the synthesized nanoplatform shows two characteristic peaks at 640.98 and 653.28 eV, corresponding to the binding energies of Mn 2p3 / 2 and Mn 2p1 / 2, respectively.

[0029] Figure 5 The image shows the UV-Vis absorption spectrum of the biodegradable functionalized silicon-based bioactive nanoplatform synthesized in Example 1 of this invention. As can be seen from the image, a characteristic absorption peak for the drug appears at 298 nm, confirming successful drug loading.

[0030] Figure 6 The figure shows the zeta potential and particle size distribution of the biodegradable functionalized silicon-based bioactive nanoplatform synthesized in Example 1 of this invention. As can be seen from the figure, bovine serum albumin was successfully coated.

[0031] Figure 7 The images show transmission electron microscopy (TEM) images of the biodegradable functionalized silicon-based bioactive nanoplatform synthesized in Example 1 undergoing biodegradation under different pH conditions. After incubation with PBS at different pH values ​​for the same amount of time, the synthesized nanoplatform exhibited significant degradation as the pH gradually decreased, eventually losing its original morphology completely.

[0032] Figure 8 and Figure 9 The biodegradable functionalized silicon-based bioactive nanoplatform synthesized in Example 1 of this invention was released in different pH media, with Mn... 2+ The graph shows the in vitro cumulative release rate of Mn²⁺ and Abe over time. As can be seen from the graph, in a simulated normal tissue physiological environment (pH 7.4), the release of both components is relatively slow within 12 hours, with cumulative release rates below 20%. Conversely, under acidic conditions simulating a microenvironment (pH 6.5), the nanoplatform undergoes rapid responsive degradation, resulting in the simultaneous rapid release of Mn²⁺ and Abe: approximately 50% burst release is achieved within the first 2 hours, and the cumulative release rate exceeds 80% within 12 hours, demonstrating the acid-responsive degradation and release characteristics of the platform of this invention.

[0033] Example 2 Preparation of a biodegradable functionalized silicon-based bioactive nanoplatform: S1. Preparation of oil phase solution: Mix 3.55 mL of chlorobenzene and 0.55 mL of tetraethyl orthosilicate in a glass container and stir magnetically at 880 r / min for 20 min to obtain a colorless and transparent homogeneous liquid system. S2. Preparation of aqueous solution: 4.85 mL of 25 wt% hexadecyltrimethylammonium chloride aqueous solution, 0.041 g of triethanolamine and 7.04 mL of deionized water are rapidly stirred at 880 r / min at room temperature for 20 min to form a homogeneous and transparent aqueous solution. S3. Weigh a certain amount of manganese chloride tetrahydrate and dissolve it in deionized water to form a 1mM solution. Sonicate the solution in an ultrasonic disperser at a frequency of 60kHz for 5 minutes to fully dissolve it into a colorless and transparent manganese chloride solution. Then, take 0.095mL of the manganese chloride solution and slowly add it dropwise to the solution in S2 at a rate of 3s / drop. Stir the mixture rapidly at 880r / min for 15 minutes at room temperature to obtain a uniformly dispersed solution. S4. The oil phase solution prepared in S1 is added dropwise to the aqueous phase solution in S3 at a rate of 3s / drop. The solution is stirred continuously at 880r / min for 12h at 60℃. The solution gradually changes from the initial colorless and transparent state to milky white. S5. The milky white mixture obtained in S4 is centrifuged at 8000 r / min for 15 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed four times with deionized water and purified by centrifugation under the same time and speed conditions to finally obtain a white solid product. S6. The white solid product obtained in S5 is dried at 80°C for 12 hours in a constant temperature drying oven and then ground into a white powder in a mortar. After that, it is calcined at 200°C for 1 hour in a muffle furnace, and then heated to 550°C for 2 hours to obtain sea urchin-like mesoporous Mn / Si nanoparticles.

[0034] S7. Dissolve the Mn / Si powder obtained in S6 in deionized water to prepare a solution of 20 mg / mL, and sonicate it at a frequency of 60 kHz for 5 min to disperse it into a uniform aqueous solution. S8. Weigh a certain amount of abexicillin powder and dissolve it in dimethyl sulfoxide to prepare an 8.296 mM solution. Sonicate the solution in an ultrasonic disperser at a frequency of 60 kHz for 5 min to fully dissolve it and form a colorless and transparent solution. Then, take 0.14 mL of the solution and slowly add it dropwise to 1 mL of the aqueous solution of S7 at a rate of 3 s / drop. Stir rapidly at a speed of 880 r / min for 14 h at room temperature. S9. The mixed solution obtained in S8 is centrifuged at 8000 r / min for 20 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed with deionized water 4 times and centrifuged under the same time and speed conditions to obtain Mn / Si-Abe nanoparticles. S10. Weigh a certain amount of bovine serum albumin and add it to deionized water to prepare a 20 mg / mL solution. Stir at 880 r / min for 15 min at room temperature to ensure complete dissolution. Then, place it in an ultrasonic disperser and sonicate at 80 kHz for 15 min to obtain a uniformly dispersed, transparent, pale yellow solution. Dissolve the Mn / Si-Abe nanoparticles obtained in S9 in deionized water to prepare a 5 mg / mL solution. Sonicate at 80 kHz for 5 min to ensure uniform dispersion. Take 1 mL of this solution and add it dropwise to 2.5 mL of the above aqueous solution at a rate of 3 s / drop. Stir rapidly at 880 r / min for 14 h at room temperature. S11. The mixed solution obtained in S8 is centrifuged at 8000 r / min for 10 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed four times with deionized water and purified by centrifugation under the same time and speed conditions to remove excess bovine serum albumin, thus obtaining the degradable functionalized silicon-based bioactive nanoplatform Mn / Si-Abe@BSA.

[0035] Example 3 Preparation of a biodegradable functionalized silicon-based bioactive nanoplatform: S1. Preparation of oil phase solution: Mix 3.6 mL of chlorobenzene and 0.55 mL of tetraethyl orthosilicate in a glass container and stir magnetically at 880 r / min for 20 min to obtain a colorless and transparent homogeneous liquid system. S2. Preparation of aqueous solution: 4.9 mL of 25 wt% hexadecyltrimethylammonium chloride aqueous solution, 0.042 g of triethanolamine and 7.08 mL of deionized water are rapidly stirred at 880 r / min at room temperature for 20 min to form a homogeneous and transparent aqueous solution. S3. Weigh a certain amount of manganese chloride tetrahydrate and dissolve it in deionized water to form a 1mM solution. Sonicate the solution in an ultrasonic disperser at a frequency of 60kHz for 5 minutes to fully dissolve it into a colorless and transparent manganese chloride solution. Then, take 0.09mL of the manganese chloride solution and slowly add it dropwise to the solution in S2 at a rate of 3s / drop. Stir the mixture rapidly at 880r / min for 15 minutes at room temperature to obtain a uniformly dispersed solution. S4. The oil phase solution prepared in S1 is added dropwise to the aqueous phase solution in S3 at a rate of 3s / drop. The solution is stirred continuously at 880r / min for 12h at 60℃. The solution gradually changes from the initial colorless and transparent state to milky white. S5. The milky white mixture obtained in S4 is centrifuged at 8000 r / min for 15 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed 5 times with deionized water and purified by centrifugation under the same time and speed conditions to finally obtain a white solid product. S6. The white solid product obtained in S5 is dried at 80°C for 12 hours in a constant temperature drying oven and then ground into a white powder in a mortar. After that, it is calcined at 200°C for 1 hour in a muffle furnace, and then heated to 550°C for 2 hours to obtain sea urchin-like mesoporous Mn / Si nanoparticles.

[0036] S7. Dissolve the Mn / Si powder obtained in S6 in deionized water to prepare a solution of 20 mg / mL, and sonicate it at a frequency of 60 kHz for 5 min to disperse it into a uniform aqueous solution. S8. Weigh a certain amount of abexicillin powder and dissolve it in dimethyl sulfoxide to prepare an 8.296 mM solution. Sonicate the solution in an ultrasonic disperser at a frequency of 60 kHz for 5 min to fully dissolve it and form a colorless and transparent solution. Then, take 0.16 mL of the solution and slowly add it dropwise to 1 mL of the aqueous solution of S7 at a rate of 3 s / drop. Stir rapidly at a speed of 880 r / min for 16 h at room temperature. S9. The mixed solution obtained in S8 is centrifuged at 8000 r / min for 20 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed with deionized water 5 times and centrifuged under the same time and speed conditions to obtain Mn / Si-Abe nanoparticles. S10. Weigh a certain amount of bovine serum albumin and add it to deionized water to prepare a 20 mg / mL solution. Stir at 880 r / min for 15 min at room temperature to ensure complete dissolution. Then, place it in an ultrasonic disperser and sonicate at 80 kHz for 15 min to obtain a uniformly dispersed, transparent, pale yellow solution. Dissolve the Mn / Si-Abe nanoparticles obtained in S9 in deionized water to prepare a 5 mg / mL solution. Sonicate at 80 kHz for 5 min to ensure uniform dispersion. Take 1 mL of this solution and add it dropwise to 2.5 mL of the above aqueous solution at a rate of 3 s / drop. Stir rapidly at 880 r / min for 16 h at room temperature. S11. The mixed solution obtained in S8 is centrifuged at 8000 r / min for 10 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed 5 times with deionized water and centrifuged under the same time and speed conditions to remove excess bovine serum albumin, thus obtaining the degradable functionalized silicon-based bioactive nanoplatform Mn / Si-Abe@BSA.

[0037] Example 4 Preparation of a biodegradable functionalized silicon-based bioactive nanoplatform: S1. Preparation of oil phase solution: Mix 3.65 mL of chlorobenzene and 0.55 mL of tetraethyl orthosilicate in a glass container and stir magnetically at 880 r / min for 20 min to obtain a colorless and transparent homogeneous liquid system. S2. Preparation of aqueous solution: 4.95 mL of 25 wt% hexadecyltrimethylammonium chloride aqueous solution, 0.043 g of triethanolamine and 7.12 mL of deionized water are rapidly stirred at 880 r / min at room temperature for 25 min to form a homogeneous and transparent aqueous solution. S3. Weigh a certain amount of manganese chloride tetrahydrate and dissolve it in deionized water to form a 1mM solution. Sonicate the solution in an ultrasonic disperser at a frequency of 60kHz for 5 minutes to fully dissolve it into a colorless and transparent manganese chloride solution. Then, take 0.105mL of the manganese chloride solution and slowly add it dropwise to the solution in S2 at a rate of 3s / drop. Stir the mixture rapidly at 880r / min for 15 minutes at room temperature to obtain a uniformly dispersed solution. S4. The oil phase solution prepared in S1 is added dropwise to the aqueous phase solution in S3 at a rate of 3s / drop. The solution is stirred continuously at 880r / min for 12h at 60℃. The solution gradually changes from the initial colorless and transparent state to milky white. S5. The milky white mixture obtained in S4 is centrifuged at 8000 r / min for 15 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed three times with deionized water and purified by centrifugation under the same time and speed conditions to finally obtain a white solid product. S6. The white solid product obtained in S5 is dried at 80°C for 12 hours in a constant temperature drying oven and then ground into a white powder in a mortar. After that, it is calcined at 200°C for 1 hour in a muffle furnace, and then heated to 550°C for 2 hours to obtain sea urchin-like mesoporous Mn / Si nanoparticles.

[0038] S7. Dissolve the Mn / Si powder obtained in S6 in deionized water to prepare a solution of 20 mg / mL, and sonicate it at a frequency of 60 kHz for 5 min to disperse it into a uniform aqueous solution. S8. Weigh a certain amount of abexicillin powder and dissolve it in dimethyl sulfoxide to prepare an 8.296 mM solution. Sonicate the solution in an ultrasonic disperser at a frequency of 60 kHz for 5 min to fully dissolve it and form a colorless and transparent solution. Then, take 0.18 mL of the solution and slowly add it dropwise to 1 mL of the aqueous solution of S7 at a rate of 3 s / drop. Stir rapidly at a speed of 880 r / min for 18 h at room temperature. S9. The mixed solution obtained in S8 is centrifuged at 8000 r / min for 20 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed three times with deionized water and purified by centrifugation under the same time and speed conditions to obtain Mn / Si-Abe nanoparticles. S10. Weigh a certain amount of bovine serum albumin and add it to deionized water to prepare a 20 mg / mL solution. Stir at 880 r / min for 15 min at room temperature to ensure complete dissolution. Then, place it in an ultrasonic disperser and sonicate at 80 kHz for 15 min to obtain a uniformly dispersed, transparent, pale yellow solution. Dissolve the Mn / Si-Abe nanoparticles obtained in S9 in deionized water to prepare a 5 mg / mL solution. Sonicate at 80 kHz for 5 min to ensure uniform dispersion. Take 1 mL of this solution and add it dropwise to 2.5 mL of the above aqueous solution at a rate of 3 s / drop. Stir rapidly at 880 r / min for 18 h at room temperature. S11. The mixed solution obtained in S8 is centrifuged at 8000 r / min for 10 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed three times with deionized water and centrifuged under the same time and speed conditions to remove excess bovine serum albumin, thus obtaining the degradable functionalized silicon-based bioactive nanoplatform Mn / Si-Abe@BSA.

[0039] Example 5 Preparation of a biodegradable functionalized silicon-based bioactive nanoplatform: S1. Preparation of oil phase solution: Mix 3.7 mL of chlorobenzene and 0.55 mL of tetraethyl orthosilicate in a glass container and stir magnetically at 880 r / min for 20 min to obtain a colorless and transparent homogeneous liquid system. S2. Preparation of aqueous solution: Mix 5 mL of 25 wt% hexadecyltrimethylammonium chloride aqueous solution, 0.044 g of triethanolamine and 7.16 mL of deionized water at room temperature at a speed of 880 r / min for 30 min to form a homogeneous and transparent aqueous solution. S3. Weigh a certain amount of manganese chloride tetrahydrate and dissolve it in deionized water to form a 1mM solution. Sonicate the solution in an ultrasonic disperser at a frequency of 60kHz for 5 minutes to fully dissolve it into a colorless and transparent manganese chloride solution. Then, take 0.11mL of the manganese chloride solution and slowly add it dropwise to the solution in S2 at a rate of 3s / drop. Stir the mixture rapidly at 880r / min for 15 minutes at room temperature to obtain a uniformly dispersed solution. S4. The oil phase solution prepared in S1 is added dropwise to the aqueous phase solution in S3 at a rate of 3s / drop. The solution is stirred continuously at 880r / min for 12h at 60℃. The solution gradually changes from the initial colorless and transparent state to milky white. S5. The milky white mixture obtained in S4 is centrifuged at 8000 r / min for 15 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed four times with deionized water and purified by centrifugation under the same time and speed conditions to finally obtain a white solid product. S6. The white solid product obtained in S5 is dried at 80°C for 12 hours in a constant temperature drying oven and then ground into a white powder in a mortar. After that, it is calcined at 200°C for 1 hour in a muffle furnace, and then heated to 550°C for 2 hours to obtain sea urchin-like mesoporous Mn / Si nanoparticles.

[0040] S7. Dissolve the Mn / Si powder obtained in S6 in deionized water to prepare a solution of 20 mg / mL, and sonicate it at a frequency of 60 kHz for 5 min to disperse it into a uniform aqueous solution. S8. Weigh a certain amount of abexicillin powder and dissolve it in dimethyl sulfoxide to prepare an 8.296 mM solution. Sonicate the solution in an ultrasonic disperser at a frequency of 60 kHz for 5 min to fully dissolve it and form a colorless and transparent solution. Then, take 0.2 mL of the solution and slowly add it dropwise to 1 mL of the aqueous solution of S7 at a rate of 3 s / drop. Stir rapidly at a speed of 880 r / min for 20 h at room temperature. S9. The mixed solution obtained in S8 is centrifuged at 8000 r / min for 20 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed with deionized water 4 times and centrifuged under the same time and speed conditions to obtain Mn / Si-Abe nanoparticles. S10. Weigh a certain amount of bovine serum albumin and add it to deionized water to prepare a 20 mg / mL solution. Stir at 880 r / min for 15 min at room temperature to ensure complete dissolution. Then, place it in an ultrasonic disperser and sonicate at 80 kHz for 15 min to obtain a uniformly dispersed, transparent, pale yellow solution. Dissolve the Mn / Si-Abe nanoparticles obtained in S9 in deionized water to prepare a 5 mg / mL solution. Sonicate at 80 kHz for 5 min to ensure uniform dispersion. Take 1 mL of this solution and add it dropwise to 2.5 mL of the above aqueous solution at a rate of 3 s / drop. Stir rapidly at 880 r / min for 20 h at room temperature. S11. The mixed solution obtained in S8 is centrifuged at 8000 r / min for 10 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed four times with deionized water and purified by centrifugation under the same time and speed conditions to remove excess bovine serum albumin, thus obtaining the degradable functionalized silicon-based bioactive nanoplatform Mn / Si-Abe@BSA.

[0041] Example 6 Preparation of a biodegradable functionalized silicon-based bioactive nanoplatform: S1. Preparation of oil phase solution: Mix 3.8 mL of chlorobenzene and 0.55 mL of tetraethyl orthosilicate in a glass container and stir magnetically at 880 r / min for 20 min to obtain a colorless and transparent homogeneous liquid system. S2. Preparation of aqueous solution: 4.9 mL of 25 wt% hexadecyltrimethylammonium chloride aqueous solution, 0.045 g of triethanolamine and 7.18 mL of deionized water are rapidly stirred at 880 r / min at room temperature for 20 min to form a homogeneous and transparent aqueous solution. S3. Weigh a certain amount of manganese chloride tetrahydrate and dissolve it in deionized water to form a 1mM solution. Sonicate the solution in an ultrasonic disperser at a frequency of 60kHz for 5 minutes to fully dissolve it into a colorless and transparent manganese chloride solution. Then, take 0.1mL of the manganese chloride solution and slowly add it dropwise to the solution in S2 at a rate of 3s / drop. Stir the mixture rapidly at 880r / min for 15 minutes at room temperature to obtain a uniformly dispersed solution. S4. The oil phase solution prepared in S1 is added dropwise to the aqueous phase solution in S3 at a rate of 3s / drop. The solution is stirred continuously at 880r / min for 12h at 60℃. The solution gradually changes from the initial colorless and transparent state to milky white. S5. The milky white mixture obtained in S4 is centrifuged at 8000 r / min for 15 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed three times with deionized water and purified by centrifugation under the same time and speed conditions to finally obtain a white solid product. S6. The white solid product obtained in S5 is dried at 80°C for 12 hours in a constant temperature drying oven and then ground into a white powder in a mortar. After that, it is calcined at 200°C for 1 hour in a muffle furnace, and then heated to 550°C for 2 hours to obtain sea urchin-like mesoporous Mn / Si nanoparticles.

[0042] S7. Dissolve the Mn / Si powder obtained in S6 in deionized water to prepare a solution of 20 mg / mL, and sonicate it at a frequency of 60 kHz for 5 min to disperse it into a uniform aqueous solution. S8. Weigh a certain amount of abexicillin powder and dissolve it in dimethyl sulfoxide to prepare an 8.296 mM solution. Sonicate the solution in an ultrasonic disperser at a frequency of 60 kHz for 5 min to fully dissolve it and form a colorless and transparent solution. Then, take 0.16 mL of the solution and slowly add it dropwise to 1 mL of the aqueous solution of S7 at a rate of 3 s / drop. Stir rapidly at a speed of 880 r / min for 24 h at room temperature. S9. The mixed solution obtained in S8 is centrifuged at 8000 r / min for 20 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed with deionized water 4 times and centrifuged under the same time and speed conditions to obtain Mn / Si-Abe nanoparticles. S10. Weigh a certain amount of bovine serum albumin and add it to deionized water to prepare a 20 mg / mL solution. Stir at 880 r / min for 15 min at room temperature to ensure complete dissolution. Then, place it in an ultrasonic disperser and sonicate at 80 kHz for 15 min to obtain a uniformly dispersed, transparent, pale yellow solution. Dissolve the Mn / Si-Abe nanoparticles obtained in S9 in deionized water to prepare a 5 mg / mL solution. Sonicate at 80 kHz for 5 min to ensure uniform dispersion. Take 1 mL of this solution and add it dropwise to 2.5 mL of the above aqueous solution at a rate of 3 s / drop. Stir rapidly at 880 r / min for 24 h at room temperature. S11. The mixed solution obtained in S8 is centrifuged at 8000 r / min for 10 min to achieve solid-liquid separation and collect the precipitate. The precipitate is then washed 5 times with deionized water and centrifuged under the same time and speed conditions to remove excess bovine serum albumin, thus obtaining the degradable functionalized silicon-based bioactive nanoplatform Mn / Si-Abe@BSA.

[0043] The above description only illustrates the preferred embodiments of the present invention. However, the present invention is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the spirit of the present invention, and all such changes should be included within the protection scope of the present invention.

Claims

1. A method for preparing a degradable functionalized silicon-based bioactive nanoplatform, characterized in that: Includes the following steps: S1. Mix the swelling agent and silicon source in a certain proportion, and stir at 880 r / min for 20 min to obtain a colorless and transparent homogeneous liquid system, i.e., an oil phase solution. S2. Mix the structure-directing agent, catalyst and deionized water in a certain proportion, and stir at 880 r / min for 15-30 min at room temperature to form a homogeneous and transparent solution. S3. Weigh out the inorganic manganese source and dissolve it in deionized water. Sonicate the solution at 60 kHz for 5 min to form a uniformly dispersed manganese source solution. Then add the solution to S2 dropwise at a rate of 3 s / drop. Stir the solution at 880 r / min for 15 min at room temperature to obtain a uniformly dispersed aqueous solution. S4. The oil phase solution prepared in S1 is added dropwise to the aqueous phase solution in S3 at a rate of 3s / drop. The solution is stirred at 880r / min for 12h at 60℃. The solution gradually changes from the initial colorless and transparent state to milky white. S5. The milky white mixture obtained in S4 is centrifuged at a speed of 8000 r / min for 15 min to achieve solid-liquid separation. The precipitate is collected, washed with water 3-5 times and purified by centrifugation to finally obtain a white solid product. S6. Dry, grind and calcine the white solid product obtained in S5 to obtain mesoporous Mn / Si nanoparticles. S7. Dissolve the mesoporous Mn / Si nanoparticles obtained in S6 in deionized water, and disperse them into a uniform aqueous solution after ultrasonic treatment. The concentration of the aqueous solution is 20 mg / mL, the volume is 1 mL, the ultrasonic frequency is 60 kHz, and the ultrasonic time is 5 min. S8. Weigh abexicillin powder and dissolve it in dimethyl sulfoxide solution. After ultrasonic dispersion and dissolution to form a colorless and transparent abexicillin solution, slowly add it dropwise to the aqueous solution in S7. Stir rapidly at room temperature to obtain a mixed solution. The ultrasonic frequency is 60 kHz, the ultrasonic treatment time is 5 min, the dropping rate is 3 s / drop, the stirring speed at room temperature is 880 r / min, and the stirring time is 12-24 h. S9. The mixed solution obtained in S8 is purified by multiple high-speed centrifugations and water washing to obtain Mn / Si-Abe nanoparticles; the high-speed centrifugation speed is 8000 r / min, the centrifugation time is 20 min, and the number of washing times is 3-5. S10. Weigh bovine serum albumin and add it to deionized water. Stir at 880 r / min for 15 min at room temperature until fully dissolved. Then, sonicate at 80 kHz for 15 min to form a transparent, pale yellow bovine serum albumin aqueous solution. Dissolve the Mn / Si-Abe nanoparticles obtained in S9 in deionized water and sonicate at 80 kHz for 5 min to form a uniform Mn / Si-Abe nanoparticle aqueous solution. Then, add the Mn / Si-Abe nanoparticles dropwise to the bovine serum albumin aqueous solution at a rate of 3 s / drop. Stir at 880 r / min for 12-24 h at room temperature to obtain a mixed solution. S11. The mixed solution obtained in S10 is subjected to multiple high-speed centrifugation and water washing purification to remove excess bovine serum albumin, thereby obtaining the degradable functionalized silicon-based bioactive nanoplatform Mn / Si-Abe@BSA; the high-speed centrifugation speed is 8000 r / min, the centrifugation time is 10 min, and the number of washing times is 3-5.

2. The method for preparing a biodegradable functionalized silicon-based bioactive nanoplatform according to claim 1, characterized in that: In S1, the swelling agent is chlorobenzene, and the silicon source is tetraethyl orthosilicate; the ratio of the swelling agent to the silicon source is 3.5-3.85 mL: 0.55 mL.

3. The method for preparing a biodegradable functionalized silicon-based bioactive nanoplatform according to claim 1, characterized in that: In S2, the structure directing agent is a 25wt% aqueous solution of hexadecyltrimethylammonium chloride, and the catalyst is triethanolamine; the ratio of the structure directing agent, catalyst, and deionized water is 4.8-5mL: 0.04-0.045g: 7-7.2mL.

4. The method for preparing a biodegradable functionalized silicon-based bioactive nanoplatform according to claim 1, characterized in that: In S3, the inorganic manganese source is manganese chloride tetrahydrate, the concentration of the manganese source solution is 1 mM, and the amount used is 0.00-0.11 mL.

5. The method for preparing a biodegradable functionalized silicon-based bioactive nanoplatform according to claim 1, characterized in that: In S6, the drying step is carried out in a constant temperature forced-air drying oven at a temperature of 80°C for 12 hours; the high-temperature calcination step is carried out in a muffle furnace using a gradient calcination method: first, heat treatment is performed at 200°C for 1 hour, followed by heating to 550°C for another 2 hours.

6. The method for preparing a biodegradable functionalized silicon-based bioactive nanoplatform according to claim 1, characterized in that: In S8, the concentration of the abecitabine solution is 8.296 mM and the volume is 0.12-0.2 mL.

7. The method for preparing a biodegradable functionalized silicon-based bioactive nanoplatform according to claim 1, characterized in that: In S10, the concentration of the bovine serum albumin aqueous solution is 20 mg / mL and the volume is 2.5-3 mL; the concentration of the Mn / Si-Abe nanoparticle aqueous solution is 5 mg / mL and the volume is 1 mL.

8. A nanoplatform prepared by the preparation method as described in claim 1 has a sea urchin-like structure with a diameter of 115-145 nm, which undergoes responsive degradation in an acidic microenvironment to release ions and drugs.

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