Silicon dioxide-ferroferric oxide magnetic particles as well as preparation method and application thereof

Abstract

The invention discloses a preparation method of silicon dioxide-ferroferric oxide magnetic particles, which comprises the following steps: A, carrying out functionalization treatment on a porous silicon dioxide film to obtain a porous silicon dioxide film with functional groups on the surface; b, dissolving anhydrous ferric trichloride in water to obtain a ferric trichloride solution; soaking the porous silicon dioxide film with functional groups on the surface in a ferric trichloride solution, taking out and heating to obtain a porous silicon dioxide film with ferric trichloride hexahydrate attached on the surface; c, performing laser processing to obtain a porous silicon dioxide film with a silicon dioxide-ferroferric oxide precursor attached to the surface; and D, performing stripping and ultrasonic oscillation on the silicon dioxide-ferroferric oxide precursor on the surface of the porous silicon dioxide film to obtain the silicon dioxide-ferroferric oxide magnetic particles. According to the preparation method of the silicon dioxide-ferroferric oxide magnetic particles provided by the invention, the obtained silicon dioxide-ferroferric oxide magnetic particles are high in suspension stability and strong in adsorption capacity.

Description

Technical Field

[0001] The present invention relates to the technical field of magnetic particles, and in particular to silicon dioxide-ferroferric oxide magnetic particles and a preparation method and application thereof. Background Art

[0002] Clustered micro-nano robots are micro-robots assembled from magnetic particles under the action of a magnetic field. They are characterized by significantly improved loading capacity and task execution efficiency. Such robots have shown broad application potential in many fields such as medicine, environmental monitoring, and precision manufacturing. Especially in the medical field, clustered micro-nano robots can accurately perform tasks such as targeted drug delivery, cell manipulation, and tissue repair, greatly promoting the innovation of minimally invasive treatment and biomedical technology. Among the many driving methods, magnetic drive technology has become the focus of current research due to its advantages of remote controllability, precise control capability, and efficient energy transmission.

[0003] As an important ferromagnetic material, ferroferric oxide has shown significant application prospects in the field of magnetically driven cluster micro-nano robots. Its strong paramagnetism and good magnetic responsiveness make the material show excellent controllability under the action of an external magnetic field. In addition, both ferroferric oxide and silicon dioxide have good biocompatibility and safety, can exist stably in the body, and can be excreted from the body through metabolic pathways, thereby minimizing the impact on cells and tissues. Therefore, the industry has emerged with the use of silicon dioxide-ferroferric oxide magnetic particles composed of ferroferric oxide and silicon dioxide, which are magnetized under the action of a magnetic field to obtain magnetically driven cluster micro-nano robots. The performance of magnetically driven cluster micro-nano robots depends on the performance of silicon dioxide-ferroferric oxide magnetic particles, making silicon dioxide-ferroferric oxide magnetic particles a key material for the preparation of magnetically driven cluster micro-nano robots.

[0004] The Chinese invention patent with the publication number CN110451581A discloses a method for preparing double-layer ferroferric oxide @ silicon dioxide magnetic composite nanoparticles, and adopts the improved Stober method to prepare double-layer ferroferric oxide @ silicon dioxide magnetic composite nanoparticles. However, since the prepared magnetic composite nanoparticles are densely structured and lack porosity, the effective contact area between them and the liquid is limited, resulting in a higher interfacial energy, which makes the particles easy to settle in the liquid, affecting the suspension stability of the magnetic composite nanoparticles in the solution, and thus making the magnetically driven cluster micro-nano robot prepared on this basis prone to near-wall effect (referring to easy sedimentation in the liquid or close to the container wall) when moving in the solution, reducing the freedom of movement and the control accuracy, thereby affecting the precise positioning. At the same time, the dense structure leads to a limited specific surface area of ​​the particles, which is limited in the adsorption capacity of drugs, thereby limiting the drug loading capacity of the magnetically driven cluster micro-nano robot.

[0005] The Chinese invention patent with publication number CN110002452A discloses a method for preparing micron-sized hollow magnetic silica microspheres, which firstly uses the Stober method to prepare hollow silica microspheres, then performs surface modification, and then uses the surface-modified hollow silica microspheres to adsorb Fe in a salt solution. 3+ and Fe 2+ , Fe 3+ and Fe 2+ Magnetic ferroferric oxide nanoparticles are deposited on the outer and inner surfaces of hollow silica microspheres to obtain micron-sized hollow magnetic silica microspheres. However, in this process, ferroferric oxide is easy to directly precipitate inside the hollow pores of the hollow silica microspheres, resulting in the clogging of the hollow pores, making it difficult for the final micron-sized hollow magnetic silica microspheres to adsorb drugs, thereby weakening the drug-carrying capacity of the magnetically driven cluster micro-nano robot constructed with it. In addition, the preparation method is relatively complicated and easily increases the difficulty of preparation.

[0006] In summary, existing silicon dioxide-iron oxide magnetic particles generally have problems such as complex preparation methods, poor suspension stability and weak adsorption capacity. Summary of the invention

[0007] One of the purposes of the present invention is to provide a method for preparing silicon dioxide-ferroferric oxide magnetic particles. The preparation method is simple and has a fast processing speed. The obtained silicon dioxide-ferroferric oxide magnetic particles not only have high suspension stability but also have strong adsorption capacity, so as to overcome the shortcomings of the prior art.

[0008] The second object of the present invention is to provide a silicon dioxide-iron tetroxide magnetic particle, which has not only high suspension stability but also strong adsorption capacity.

[0009] The third purpose of the present invention is to provide an application of silicon dioxide-iron tetroxide magnetic particles, which are used to prepare magnetically driven cluster micro-nano robots. The obtained magnetically driven cluster micro-nano robots have a drug loading rate of up to 80-85%. They not only have strong drug loading capacity but also have precise positioning, which can greatly meet practical application needs.

[0010] To achieve this object, the present invention adopts the following technical solutions:

[0011] A method for preparing silicon dioxide-ferroferric oxide magnetic particles comprises the following steps:

[0012] A. preparing a porous silica film; performing functional treatment on the porous silica film to obtain a porous silica film with functional groups on the surface; wherein the functional groups are used to bind to drug molecules and to form charged groups in the solution;

[0013] B. dissolving anhydrous ferric chloride in water and stirring to obtain a ferric chloride solution; immersing the porous silica film with functional groups on the surface in step A in the ferric chloride solution, taking it out and heating it to obtain a porous silica film with ferric chloride hexahydrate attached to the surface;

[0014] C. laser processing the porous silica film with ferric chloride hexahydrate attached to the surface in step B to obtain a porous silica film with a silica-ferroferric oxide precursor attached to the surface;

[0015] D. peeling off the silica-ferroferric oxide precursor on the surface of the porous silica film in step C to obtain a silica-ferroferric oxide precursor; ultrasonically vibrating the silica-ferroferric oxide precursor to obtain silica-ferroferric oxide magnetic particles.

[0016] Furthermore, in step A, the method for preparing the porous silicon dioxide film is specifically as follows:

[0017] The silica precursor solution is coated on the surface of the substrate, and the substrate with silica gel attached to the surface is obtained after laser processing;

[0018] The substrate with the silica gel attached to the surface is placed in a mixed solution of ethanol and water to obtain a substrate with a porous silica film attached to the surface;

[0019] The porous silicon dioxide film is peeled off from the surface of the substrate to obtain a porous silicon dioxide film;

[0020] The raw materials of the silicon dioxide precursor solution include a template, a tetraethyl orthosilicate solution and a hydrochloric acid solution, and the mixing ratio of the template, the tetraethyl orthosilicate solution and the hydrochloric acid solution is (0.1-0.3):1:(0.001-0.005) calculated by volume ratio;

[0021] The raw materials of the tetraethyl orthosilicate solution include tetraethyl orthosilicate, anhydrous ethanol and water, and calculated by molar ratio, the mixing ratio of the tetraethyl orthosilicate, the anhydrous ethanol and the water is 1:(2-6):(8-12).

[0022] Further, in step A, the functionalization treatment is an amination treatment or a carboxylation treatment;

[0023] The functional group includes any one of an amino group and a carboxyl group.

[0024] Furthermore, the specific method of the amination treatment is: laser processing the porous silica film to obtain a porous silica film with increased surface activity; coating the amination precursor solution on the surface of the porous silica film with increased surface activity, and heating at 50 to 60° C. for 0.5 to 0.6 h to obtain an amination-treated porous silica film;

[0025] The raw materials of the amination precursor solution include 3-aminopropyltriethoxysilane solution and acetic acid solution; the raw materials of the 3-aminopropyltriethoxysilane solution include 3-aminopropyltriethoxysilane, anhydrous ethanol and water.

[0026] Furthermore, the specific method of the carboxylation treatment is: laser processing the porous silica film to obtain a porous silica film with increased surface activity; coating the carboxylation precursor solution on the surface of the porous silica film with increased surface activity, and heating it at 50 to 60° C. for 0.5 to 0.6° C. to obtain a carboxylation-treated porous silica film;

[0027] Wherein, the raw materials of the carboxylation precursor solution include chloroacetic acid and water.

[0028] Further, in step B, the mixing ratio of the anhydrous ferric chloride to the water is 1:(2-4) calculated by mass ratio;

[0029] In step B, the heating temperature is 60-80°C.

[0030] Furthermore, in step C, the laser wavelength of the laser processing is 350-360 nm, and the laser power is 10-15 W.

[0031] Furthermore, in step D, the ultrasonic oscillation time is 3 to 5 minutes and the frequency is 30 to 40 kHz.

[0032] A silicon dioxide-ferroferric oxide magnetic particle is prepared by using the above-mentioned method for preparing a silicon dioxide-ferroferric oxide magnetic particle.

[0033] An application of a silicon dioxide-iron tetroxide magnetic particle in the preparation of a magnetically driven cluster micro-nano robot, using the above-mentioned silicon dioxide-iron tetroxide magnetic particle, and the application method is: the silicon dioxide-iron tetroxide magnetic particle is placed in a polyvinyl pyrrolidone solution for dispersion, and a rotating magnetic field is applied to magnetize to obtain a magnetically driven cluster micro-nano robot;

[0034] Wherein, calculated by mass percentage, the content of polyvinyl pyrrolidone in the polyvinyl pyrrolidone solution is 2-5%;

[0035] The shape of the magnetically driven cluster micro-nano robot is circular or elliptical, and the drug loading rate is 80-85%.

[0036] The technical solution provided by the present invention may include the following beneficial effects:

[0037] 1. By making the porous silica film have a porous structure, the silica-iron tetroxide magnetic particles also have a porous structure, and the porous structure of the silica-iron tetroxide magnetic particles increases its contact area with the liquid and reduces the interfacial energy, which is conducive to maintaining a uniform dispersion state, preventing phase separation and sedimentation, and thus helping to improve its suspension stability. In addition, the pores in the porous structure can retain liquid to form a liquid-solid composite system, and the retained liquid further reduces the effective density of the silica-iron tetroxide magnetic particles, making it closer to the density of the liquid, thereby increasing the suspension stability. It should be noted that the porosity and pore size of the porous silica film in this scheme can be adjusted, so that the density of the silica-iron tetroxide magnetic particles finally obtained can be adjusted according to the actual application scenario, which is also conducive to enhancing the suspension stability. Further, through functionalization treatment, the silica-iron tetroxide magnetic particles finally obtained are introduced with functional groups (such as -NH 2 and / or -COOH), while functional groups are easily protonated or ionized in liquids to form charged groups (such as -NH 3 + and / or -COO - ), so that the silicon dioxide-iron tetroxide magnetic particles produce electrostatic repulsion in the liquid, preventing the particles from agglomerating and settling, which is also beneficial to increase its suspension stability.

[0038] 2. Silica has the characteristic of being porous and having high specific surface area, so that the finally obtained silica-iron tetroxide magnetic particles have higher adsorption capacity to medicine, thereby improving adsorption capacity. Meanwhile, the porosity and pore size of porous silica film in the present application are adjustable, and appropriate porosity and pore size can ensure that the target molecule can smoothly enter the pore and be effectively adsorbed, and are also conducive to improving adsorption capacity. In addition, the technical scheme is processed by functionalization, so that the finally obtained silica-iron tetroxide magnetic particles have functional groups, and the functional groups can form stable complexes with drug molecules (such as DNA, RNA, antibodies or chemotherapeutics), which is conducive to improving adsorption capacity. In addition, the functionalization treatment not only introduces functional groups, but also increases the roughness of the finally obtained silica-iron tetroxide magnetic particles surface, thereby increasing specific surface area, and larger specific surface area provides more adsorption sites for drug molecules, thereby improving adsorption capacity. DETAILED DESCRIPTION

[0039] The present invention provides a method for preparing silicon dioxide-ferroferric oxide magnetic particles, comprising the following steps:

[0040] A. preparing a porous silica film; performing functional treatment on the porous silica film to obtain a porous silica film with functional groups on the surface; wherein the functional groups are used to bind to drug molecules and to form charged groups in the solution;

[0041] B. dissolving anhydrous ferric chloride in water and stirring to obtain a ferric chloride solution; immersing the porous silica film with functional groups on the surface in step A in the ferric chloride solution, taking it out and heating it to obtain a porous silica film with ferric chloride hexahydrate attached to the surface;

[0042] C. laser processing the porous silica film with ferric chloride hexahydrate attached to the surface in step B to obtain a porous silica film with a silica-ferroferric oxide precursor attached to the surface;

[0043] D. peeling off the silica-ferroferric oxide precursor on the surface of the porous silica film in step C to obtain a silica-ferroferric oxide precursor; ultrasonically vibrating the silica-ferroferric oxide precursor to obtain silica-ferroferric oxide magnetic particles.

[0044] In the prior art, the improved Stober method is used to prepare double-layer ferroferric oxide@silicon dioxide magnetic composite nanoparticles. However, since the prepared magnetic composite nanoparticles have a dense structure and lack porosity, they have poor suspension stability and weak adsorption capacity. In addition, the prior art uses the Stober method and the deposition method to prepare silicon dioxide-ferroferric oxide magnetism, which not only makes the preparation method complicated, but also leads to poor suspension stability and weak adsorption capacity.

[0045] In order to overcome the problems of complex preparation methods and weak adsorption capacity in the prior art, this technical solution proposes a method for preparing silicon dioxide-iron tetroxide magnetic particles, including four steps of A (functionalization treatment), B (immersion in ferric chloride solution), C (laser processing) and D (peeling). The obtained silicon dioxide-iron tetroxide magnetic particles not only have high suspension stability, but also have strong adsorption capacity. At the same time, the preparation method of this technical solution is simple, the processing speed is fast, and the production efficiency of the product is improved.

[0046] Specifically, the technical solution makes the silica-iron tetroxide magnetic particles also have a porous structure by making the porous silica film have a porous structure, and the porous structure of the silica-iron tetroxide magnetic particles increases its contact area with the liquid and reduces the interfacial energy, which is conducive to maintaining a uniform dispersion state, preventing phase separation and sedimentation, and thus helping to improve its suspension stability. In addition, the pores in the porous structure can retain liquid to form a liquid-solid composite system, and the retained liquid further reduces the effective density of the silica-iron tetroxide magnetic particles, making it closer to the density of the liquid, thereby increasing the suspension stability. It should be noted that the porosity and pore size of the porous silica film in this solution can be adjusted, so that the density of the silica-iron tetroxide magnetic particles finally obtained can be adjusted according to the actual application scenario, which is also conducive to enhancing the suspension stability. Further, by functionalization treatment, the silica-iron tetroxide magnetic particles finally obtained are introduced with functional groups (such as -NH 2 and / or -COOH), while functional groups are easily protonated or ionized in liquids to form charged groups (such as -NH 3 + and / or -COO - ), so that the silicon dioxide-iron tetroxide magnetic particles generate electrostatic repulsion in the liquid, preventing the particles from agglomerating and settling, and also helping to increase their suspension stability. That is, the present application uses the above-mentioned multiple effects to make the silicon dioxide-iron tetroxide magnetic particles obtained by using the technical solution have suspension stability.

[0047] Further, the silica of the technical solution has the characteristics of being porous and having a high specific surface area, so that the finally obtained silica-iron tetroxide magnetic particles have a higher adsorption capacity for drugs, thereby improving the adsorption capacity. Meanwhile, the porosity and pore size of the porous silica film in the present application are adjustable, and the appropriate porosity and pore size can ensure that the target molecule can smoothly enter the pore and be effectively adsorbed, which is also conducive to improving the adsorption capacity. In addition, the present technical solution is processed by functionalization, so that the finally obtained silica-iron tetroxide magnetic particles have functional groups, and the functional groups can form a stable complex with drug molecules (such as DNA, RNA, antibodies or chemotherapeutic drugs), which is conducive to improving the adsorption capacity. In addition, the functionalization treatment not only introduces functional groups, but also increases the roughness of the surface of the finally obtained silica-iron tetroxide magnetic particles, thereby increasing the specific surface area, and the larger specific surface area provides more adsorption sites for drug molecules, thereby improving the adsorption capacity. In summary, the present application is through the above-mentioned multi-faceted effects, so that the silica-iron tetroxide magnetic particles have extremely strong adsorption capacity.

[0048] It should be noted that although the silica layer is located inside the silica-ferroferric oxide magnetic particles obtained after laser processing, the internal silica layer still retains the functional groups and porous structure introduced by the functionalization treatment, so that its adsorption and suspension capabilities are still maintained or enhanced.

[0049] Furthermore, this technical solution only requires two basic raw materials and can produce the target product through simple processing, which not only reduces the cost but also enhances the controllability of the operation, laying a solid foundation for subsequent industrial applications. During the preparation process, the application of laser processing technology has shown the following advantages: (1) Laser processing has achieved a significant increase in processing speed and significantly improved production efficiency; (2) The stability of laser energy is conducive to ensuring the performance consistency of the prepared silicon dioxide-iron tetroxide magnetic particles, thereby improving the performance stability of the product.

[0050] More specifically, since the ferric chloride aqueous solution itself contains a large amount of water, it is easy to cause laser energy dissipation during laser processing, and it is impossible to process a silicon dioxide-iron tetroxide precursor with high consistency. Therefore, the technical solution adopts heating measures, and by heating the ferric chloride aqueous solution, ferric chloride hexahydrate compounds are precipitated on the surface of the porous silicon dioxide film, and then the ferric chloride hexahydrate is processed by laser to obtain a silicon dioxide-iron tetroxide precursor with high consistency.

[0051] In the laser processing step of step B, the laser causes the ferric chloride hexahydrate to undergo an oxidation-reduction reaction to generate ferroferric oxide nanoparticles. In this process, the ferroferric oxide magnetic particles are tightly combined with the porous silicon dioxide film with functional groups on the surface to form a silicon dioxide-ferroferric oxide precursor.

[0052] It should be noted that in the process of laser processing, the laser does not completely penetrate the porous silica film with functional groups on the surface. Only part of the porous silica film with functional groups on the surface is combined with the ferroferric oxide magnetic particles converted from ferric chloride hexahydrate, and the other part of the porous silica film with functional groups on the surface still exists in its own form, so that the porous silica film with functional groups on the surface can be used as a carrier to carry the silica-ferroferric oxide precursor, and can also be used as a raw material to participate in the preparation of the silica-ferroferric oxide precursor, which greatly simplifies the preparation process, saves raw materials, and reduces costs. In addition, during the laser processing process, the laser beam will generate local high temperature in the action area, so that the bonding area of ​​ferroferric oxide and silica will be locally heated, thereby achieving a tight fit.

[0053] Finally, the silica-iron tetroxide precursor on the surface of the porous silica film in step C is stripped to obtain the silica-iron tetroxide precursor, and then the silica-iron tetroxide precursor is ultrasonically vibrated to obtain silica-iron tetroxide magnetic particles, and the stripping method is simple. It should be noted that in step D, the specific method of the stripping is: scraping the silica-iron tetroxide precursor on the surface of the porous silica film with a blade.

[0054] It should be noted that, in the prior art, graphene-iron tetroxide magnetic particles are generally used to prepare magnetically driven cluster micro-nano robots, but in the present technical solution, graphene-iron tetroxide magnetic particles cannot replace silicon dioxide-iron tetroxide magnetic particles. The specific reasons are as follows: (1) The lack of natural hydroxyl groups on the surface of graphene makes its surface chemical reactivity poor, and it is difficult to modify it directly through chemical methods such as carboxylation and amination; (2) Compared with silicon dioxide, graphene has poor biocompatibility and is difficult to be directly excreted from the body through metabolic pathways. As a result, the magnetically driven cluster micro-nano robots prepared using graphene-iron tetroxide magnetic particles are more suitable for use in the electronics or catalysis fields rather than in the biomedical field.

[0055] Preferably, the laser processing step of step C further includes a drying step, specifically: soaking the porous silica film with the silica-ferroferric oxide precursor attached to the surface in water, and then drying it at a temperature of 75 to 85°C.

[0056] In one embodiment of the present technical solution, a porous silica film with a silica-ferroferric oxide precursor attached to the surface is immersed in water to remove the ferric chloride hexahydrate remaining on the surface of the porous silica film, and then dried at a temperature of 75 to 85°C to remove moisture, so that the silica-ferroferric oxide precursor can be more easily peeled off from the porous silica film, thereby improving production efficiency.

[0057] Further explanation, in step A, the preparation method of the porous silicon dioxide film is specifically as follows:

[0058] The silica precursor solution is coated on the surface of the substrate, and the substrate with silica gel attached to the surface is obtained after laser processing;

[0059] The substrate with the silica gel attached to the surface is placed in a mixed solution of ethanol and water to obtain a substrate with a porous silica film attached to the surface;

[0060] The porous silicon dioxide film is peeled off from the surface of the substrate to obtain a porous silicon dioxide film;

[0061] The raw materials of the silicon dioxide precursor solution include a template, a tetraethyl orthosilicate solution and a hydrochloric acid solution, and the mixing ratio of the template, the tetraethyl orthosilicate solution and the hydrochloric acid solution is (0.1-0.3):1:(0.001-0.005) calculated by volume ratio;

[0062] The raw materials of the tetraethyl orthosilicate solution include tetraethyl orthosilicate, anhydrous ethanol and water, and calculated by molar ratio, the mixing ratio of the tetraethyl orthosilicate, the anhydrous ethanol and the water is 1:(2-6):(8-12).

[0063] The technical solution utilizes tetraethyl orthosilicate and water to undergo a hydrolysis reaction in an acidic environment provided by hydrochloric acid to generate silanol (Si-OH); the silanol further polycondenses to form a Si-O-Si network structure, thereby forming a silica gel on the surface of the substrate, and obtaining a substrate with silica gel attached to the surface. At the same time, the template (such as a surfactant) forms micelles or self-assembled structures in the solution, providing a basis for the subsequent formation of a porous structure. The template is an amphiphilic molecule, and its hydrophobic long chain is easily soluble in ethanol, and the hydrophilic head is easily soluble in water. Therefore, the substrate with silica gel attached is placed in a mixed solution of ethanol and water, the template can be removed, leaving the gaps occupied by the template, so that a uniform porous structure is formed in the silica gel, and a substrate with a porous silica film attached to the surface is obtained. Finally, the porous silica film is obtained by peeling off the porous silica film on the surface of the substrate. The preparation process of this method is simple, and the use of laser processing can accelerate the hydrolysis and polycondensation reaction of tetraethyl orthosilicate, thereby improving production efficiency.

[0064] The porosity and pore size of porous silica films are not only related to the mixing ratio of the template and tetraethyl orthosilicate solution in the silica precursor solution, but also closely related to the mixing ratio of tetraethyl orthosilicate, anhydrous ethanol and water in the tetraethyl orthosilicate solution. Specifically, if the template ratio is too high, the porosity will be low, the pore size will be too large, and the pore distribution will be uneven. If the template ratio is too low, the porosity will be high, the pore size will be too small, and the pore structure will be poorly stable and easy to collapse. If the tetraethyl orthosilicate ratio is too high, the density of the porous silica film will be too high, and the pores will be difficult to form and the size will be too small. If the tetraethyl orthosilicate ratio is too low, not only the pore size of the porous silica film will be too large, but also the density of the porous silica film will be too low, and the pore structure will collapse easily.

[0065] Therefore, the technical solution limits the ratio of the template, tetraethyl orthosilicate solution and hydrochloric acid solution in the silica precursor solution, and the ratio of tetraethyl orthosilicate, anhydrous ethanol and water in the tetraethyl orthosilicate solution, thereby ensuring that the porosity and pore size of the porous silica film are appropriate, and the porosity and pore size can be controlled.

[0066] In addition, the ratio of each component in the tetraethyl orthosilicate solution has a significant effect on the quality of the film, as shown below: (1) If the ethanol ratio is too high, the hydrolysis rate will be reduced, resulting in decreased film stability; if the ethanol ratio is too low, the solution viscosity will increase, resulting in uneven coating and difficulty in forming a high-quality film; if the water ratio is too high, the hydrolysis and polycondensation rate of tetraethyl orthosilicate will be accelerated, resulting in roughening of the product and uneven pore distribution; if the water ratio is too low, the hydrolysis rate will be reduced, resulting in an incomplete product structure and poor pore stability. Therefore, by optimizing the ratio of each component in the tetraethyl orthosilicate solution, the porosity and pore size can be precisely controlled while ensuring the quality of the porous silica film.

[0067] Preferably, the concentration of hydrochloric acid in the hydrochloric acid solution is 0.01 to 0.03 mol / L.

[0068] By limiting the concentration of hydrochloric acid in the hydrochloric acid solution, it is helpful to ensure its catalytic effect.

[0069] It should be noted that the template agent may be hexadecyl trimethyl ammonium bromide and sodium dodecyl sulfate, etc., and the specific type is not limited here. The substrate may be a glass substrate, and the specific type is also not limited here.

[0070] Further, in step A, the functionalization treatment is an amination treatment or a carboxylation treatment;

[0071] The functional group includes any one of an amino group and a carboxyl group.

[0072] The porous silica film is subjected to an amination treatment or a carboxylation treatment, so that the surface of the final product has amino or carboxyl groups. The amino and carboxyl groups are not only conducive to improving the hydrophilicity and biocompatibility of the product, making it suitable for the biomedical field, but also can interact with a variety of substances to enhance the adsorption performance of the product, making it suitable for environmental protection fields such as wastewater treatment and gas purification. Therefore, the technical solution of the porous silica film is subjected to an amination treatment or a carboxylation treatment, which is conducive to improving the performance of the product and broadening the application field.

[0073] Further, the specific method of the amination treatment is: laser processing the porous silica film to obtain a porous silica film with increased surface activity; coating the amination precursor solution on the surface of the porous silica film with increased surface activity, and heating at 50 to 60° C. for 0.5 to 0.6 h to obtain an amination-treated porous silica film;

[0074] The raw materials of the amination precursor solution include 3-aminopropyltriethoxysilane solution and acetic acid solution; the raw materials of the 3-aminopropyltriethoxysilane solution include 3-aminopropyltriethoxysilane, anhydrous ethanol and water.

[0075] Through laser processing, the local high temperature thermal effect and photochemical effect of the laser are used to locally break the molecular bonds on the surface of silica to form silanol (Si-OH). Silanol is an active site on the surface of porous silica film, which can enhance the surface activity of porous silica film and provide more favorable conditions for subsequent amination. In addition, the laser processing activation step is more efficient than traditional chemical methods, and can significantly increase the number of active sites on the surface of silica in a short time, providing more favorable conditions for subsequent amination treatment.

[0076] Furthermore, the amination precursor solution is prepared by mixing a 3-aminopropyltriethoxysilane solution and an acetic acid solution in a certain proportion. 3-aminopropyltriethoxysilane is a compound containing amino groups and ethoxysilane, which can react with the silanol groups on the surface of the porous silica film under the catalytic action of acetic acid to obtain an amination-treated porous silica film.

[0077] It should be noted that if the heating temperature is too high, the 3-aminopropyltriethoxysilane molecules will easily undergo self-polymerization reaction to generate insoluble polysilane substances, affecting the uniformity of the product surface; if the heating temperature is too low, the amination reaction rate will be reduced, resulting in insufficient degree of amination, affecting the performance of the product. Therefore, the technical solution limits the heating temperature, which is beneficial to prevent the self-polymerization reaction of 3-aminopropyltriethoxysilane molecules while improving the reaction rate. In addition, due to the high surface activity of the porous silica film after laser processing, the heating reaction time only needs to be 0.5 to 0.6 hours to complete the amination treatment, which is beneficial to improve production efficiency.

[0078] Preferably, calculated by volume ratio, the mixing ratio of the 3-aminopropyltriethoxysilane solution to the acetic acid solution is 1:(0.01-0.05);

[0079] Calculated by molar ratio, the mixing ratio of the 3-aminopropyltriethoxysilane, the anhydrous ethanol and the water is 1:(8-12):(10-15);

[0080] The concentration of acetic acid in the acetic acid solution is 0.01-0.03 mol / L.

[0081] If the proportion of 3-aminopropyltriethoxysilane solution in the amination precursor solution is too high, the excess 3-aminopropyltriethoxysilane molecules in the amination precursor solution will undergo self-polymerization to generate granular substances, affecting the quality of the product; if the proportion of 3-aminopropyltriethoxysilane solution in the amination precursor solution is too low, the degree of amination will be insufficient, affecting the performance of the product.

[0082] Further, the specific method of the carboxylation treatment is: laser processing the porous silica film to obtain a porous silica film with increased surface activity; coating the carboxylation precursor solution on the surface of the porous silica film with increased surface activity, heating at 50 to 60° C. for 0.5 to 0.6° C. to obtain a carboxylation-treated porous silica film;

[0083] Wherein, the raw materials of the carboxylation precursor solution include chloroacetic acid and water.

[0084] The carboxylation precursor solution is made by mixing chloroacetic acid and water in a certain proportion. Chloroacetic acid can react with the silanol groups on the surface of the porous silica film to obtain a carboxylation-treated porous silica film. In addition, due to the high surface activity of the porous silica film after laser processing, the heating reaction time is only 0.5 to 0.6 hours to complete the carboxylation treatment.

[0085] Preferably, calculated by volume ratio, the mixing ratio of the chloroacetic acid to the water is 1:(8-12).

[0086] By limiting the mixing ratio of chloroacetic acid and water, it is helpful to ensure the completeness of carboxylation, and further ensure the performance of the porous silica film treated with carboxylation.

[0087] Further, in step B, the mixing ratio of the anhydrous ferric chloride to the water is 1:(2-4) calculated by mass ratio;

[0088] In step B, the heating temperature is 60-80°C.

[0089] If the content of ferric chloride in the ferric chloride solution is too low, the amount of water in the ferric chloride aqueous solution will be too much, so that the ferric chloride aqueous solution needs to be heated for a long time before it can be completely precipitated as ferric chloride hexahydrate, which is easy to reduce production efficiency; in addition, the mixing ratio of anhydrous ferric chloride and deionized water is related to the amount of silicon dioxide-iron tetroxide magnetic particles obtained after laser processing. If the content of ferric chloride in the ferric chloride solution is too low, it is easy to cause the amount of silicon dioxide-iron tetroxide magnetic particles obtained after laser processing to be small. If the content of ferric chloride in the ferric chloride solution is too high, the amount of ferric chloride hexahydrate precipitated from the ferric chloride aqueous solution will be too much, resulting in a long subsequent laser processing time, affecting the processing efficiency.

[0090] Furthermore, since ferric chloride is a covalent iron salt compound, it is easily soluble in water and has strong water absorption. When the heating temperature is lower than 60°C, the precipitation speed of the ferric chloride solution into ferric chloride hexahydrate compound is too slow, affecting the processing efficiency; when the heating temperature is higher than 80°C, the ferric chloride solution is easily hydrolyzed to generate hydrogen chloride and ferric hydroxide precipitation, which affects the processing environment and subsequent laser processing. Therefore, the preferred heating temperature of the ferric chloride solution in this technical solution is 60-80°C, which is conducive to ensuring the processing rate and processing performance.

[0091] Further description, in step C, the laser wavelength of the laser processing is 350-360nm, and the laser power is 10-15W.

[0092] This technical solution limits the laser wavelength and laser power to ensure that the laser energy is sufficient to break the bonds between atoms or molecules in ferric chloride, thereby converting ferric chloride into ferroferric oxide, and the converted ferroferric oxide can be closely attached to silicon dioxide to form a silicon dioxide-ferroferric oxide precursor. At the same time, the processing using a laser with a wavelength of 350-360nm and a power of 10-15W also has the characteristics of fast processing speed, high processing accuracy and stable power, which is not only conducive to improving the consistency of the product, but also helps to avoid the occurrence of major damage to the porous silicon dioxide film during processing.

[0093] Further, in step D, the ultrasonic oscillation time is 3 to 5 minutes and the frequency is 30 to 40 kHz.

[0094] By controlling the ultrasonic oscillation time and frequency, the silicon dioxide-iron tetroxide precursor is broken up under the action of ultrasonic oscillation, which is conducive to the formation of silicon dioxide-iron tetroxide magnetic particles with a particle size of 100nm to 10μm. The silicon dioxide-iron tetroxide magnetic particles with a particle size of 100nm to 10μm have high consistency, strong magnetic field response ability and are easy to control, which is conducive to using them to prepare magnetically driven micro-nano robots with high consistency and strong manipulability.

[0095] A silicon dioxide-ferroferric oxide magnetic particle is prepared by using the above-mentioned method for preparing a silicon dioxide-ferroferric oxide magnetic particle.

[0096] The technical solution also proposes a method for preparing silicon dioxide-ferroferric oxide magnetic particles. The silicon dioxide-ferroferric oxide magnetic particles prepared by the method have high suspension stability and strong adsorption capacity.

[0097] An application of a silicon dioxide-iron tetroxide magnetic particle in the preparation of a magnetically driven cluster micro-nano robot, using the above-mentioned silicon dioxide-iron tetroxide magnetic particle, and the application method is: the silicon dioxide-iron tetroxide magnetic particle is placed in a polyvinyl pyrrolidone solution for dispersion, and a rotating magnetic field is applied to magnetize to obtain a magnetically driven cluster micro-nano robot;

[0098] Wherein, calculated by mass percentage, the content of polyvinyl pyrrolidone in the polyvinyl pyrrolidone solution is 2-5%;

[0099] The shape of the magnetically driven cluster micro-nano robot is circular or elliptical, and the drug loading rate is 80-85%.

[0100] This technical solution also proposes an application of silica-iron tetroxide magnetic particles in the preparation of magnetically driven cluster micro-nano robots, and the magnetically driven cluster micro-nano robots are obtained by magnetizing silica-iron tetroxide magnetic particles under the action of a magnetic field. The drug loading performance of the magnetically driven cluster micro-nano robots is directly related to the adsorption capacity of the silica-iron tetroxide magnetic particles; the stronger the adsorption capacity of the particles, the greater the drug loading capacity of the prepared magnetically driven cluster micro-nano robots. At the same time, the positioning accuracy of the magnetically driven cluster micro-nano robots is highly dependent on the suspension stability of the particles; the higher the suspension stability, the more accurate the positioning of the magnetically driven cluster micro-nano robots. Thanks to the high suspension stability and strong adsorption capacity of the silica-iron tetroxide magnetic particles in this technical solution, the drug loading rate of the prepared magnetically driven cluster micro-nano robots is 80-85%, which not only has a strong drug loading capacity, but also has accurate positioning, which greatly meets the needs of practical applications.

[0101] It should be noted that the silica-iron tetroxide magnetic particles can effectively prevent the agglomeration of particles due to their own suspension stability. In addition, the polyvinyl pyrrolidone solution exhibits certain viscosity and fluid resistance characteristics, which further enhance the effect of preventing the agglomeration of silica-iron tetroxide magnetic particles. The above combined advantages not only promote the stable dispersion of particles, but also facilitate the precise control of silica-iron tetroxide magnetic particles through magnetic fields, thereby facilitating the construction of magnetically driven clustered micro-nano robots.

[0102] The technical solution of the present invention is further illustrated below through specific implementation methods.

[0103] Example 1

[0104] A. Prepare a porous silica film; perform an amination treatment on the porous silica film to obtain a porous silica film with amino groups on the surface; wherein the amino groups are used to combine with drug molecules and to form charged groups in the solution; the method for preparing the porous silica film is specifically as follows: apply a silica precursor solution on the surface of a glass substrate, and obtain a glass substrate with silica gel attached to the surface after laser processing; place the glass substrate with silica gel attached to the surface into a mixed solution of ethanol and water to obtain a glass substrate with a porous silica film attached to the surface; peel off the porous silica film on the surface of the glass substrate to obtain a porous silica film; the raw materials of the silica precursor solution include hexadecyltrimethylammonium bromide, tetraethyl orthosilicate solution and hydrochloric acid solution, and the mixing ratio of hexadecyltrimethylammonium bromide, tetraethyl orthosilicate solution and hydrochloric acid solution is 0.1:1:0.001 according to the volume ratio; the hydrochloric acid The concentration of hydrochloric acid in the solution is 0.01 mol / L; the raw materials of the tetraethyl orthosilicate solution include tetraethyl orthosilicate, anhydrous ethanol and water, and the mixing ratio of tetraethyl orthosilicate, anhydrous ethanol and water is 1:2:8 according to the molar ratio; the specific method of the amination treatment is: laser processing the porous silica film to obtain a porous silica film with increased surface activity; coating the amination precursor solution on the surface of the porous silica film with increased surface activity, and heating it at 50°C for 0.6h to obtain an amination-treated porous silica film; wherein, according to the volume ratio, the mixing ratio of 3-aminopropyltriethoxysilane solution and acetic acid solution in the amination precursor solution is 1:0.01; according to the molar ratio, the mixing ratio of 3-aminopropyltriethoxysilane, anhydrous ethanol and water in the 3-aminopropyltriethoxysilane solution is 1:10:12; the concentration of acetic acid in the acetic acid solution is 0.01 mol / L;

[0105] B. dissolving anhydrous ferric chloride in water and stirring to obtain a ferric chloride solution; immersing the porous silica film with amino groups on the surface in step A in the ferric chloride solution, taking it out and heating it at 80° C. to obtain a porous silica film with ferric chloride hexahydrate attached to the surface; the mixing ratio of anhydrous ferric chloride to water is 1:2 according to the mass ratio;

[0106] C. The porous silica film with ferric chloride hexahydrate attached to the surface in step B is laser processed by using a laser with a wavelength of 350 nm and a power of 12 W to obtain a porous silica film with a silicon dioxide-ferroferric oxide precursor attached to the surface;

[0107] D. Stripping the silica-ferroferric oxide precursor on the surface of the porous silica film in step C to obtain a silica-ferroferric oxide precursor; ultrasonically oscillating the silica-ferroferric oxide precursor in an ultrasonic oscillator with an oscillation frequency of 35 kHz for 4 minutes to obtain silica-ferroferric oxide magnetic particles.

[0108] The silicon dioxide-iron tetroxide magnetic particles obtained in Example 1 are dispersed in a polyvinyl pyrrolidone solution containing 3wt% polyvinyl pyrrolidone, and a rotating magnetic field is applied to magnetize to obtain a magnetically driven cluster micro-nano robot. The magnetically driven cluster micro-nano robot is immersed in a doxorubicin solution with a concentration of 50-60μg / ml, and taken out after standing for 2 hours to obtain a magnetically driven cluster micro-nano robot loaded with doxorubicin; the magnetically driven cluster micro-nano robot is driven in a rotating magnetic field with an intensity of 8mT to target the affected area for recruitment. The concentration of the doxorubicin solution after the magnetically driven cluster micro-nano robot is immersed is measured by a fluorescence spectrophotometer, so as to calculate the drug loading rate of the magnetically driven cluster micro-nano robot, and the motion trajectory of the magnetically driven cluster micro-nano robot is observed under a microscope.

[0109] The experimental results show that the drug loading rate of the magnetically driven cluster micro-nano robot prepared in Example 1 is 85%, and it can accurately target the lesion area under the guidance of the rotating magnetic field to achieve precise positioning and delivery of doxorubicin. The drug loading performance of the magnetically driven cluster micro-nano robot is directly related to the adsorption force of the silica-iron tetroxide magnetic particles, which is specifically manifested as follows: the adsorption force of the silica-iron tetroxide magnetic particles is enhanced, and the drug loading capacity of the magnetically driven cluster micro-nano robot constructed on the basis of the silica-iron tetroxide magnetic particles is also improved. In addition, the positioning accuracy of the magnetically driven cluster micro-nano robot is closely related to the suspension stability of the silica-iron tetroxide magnetic particles; the higher the suspension stability of the silica-iron tetroxide magnetic particles, the more accurate the positioning of the prepared magnetically driven cluster micro-nano robot. The performance of the magnetically driven cluster micro-nano robot shown in Example 1 verifies that the silica-iron tetroxide magnetic particles in this technical solution have excellent suspension stability and strong adsorption capacity.

[0110] Example 2

[0111] A. preparing a porous silica film; performing carboxyl treatment on the porous silica film to obtain a porous silica film with carboxyl groups on the surface; wherein the carboxyl groups are used to combine with drug molecules and to form charged groups in the solution; the method for preparing the porous silica film is specifically as follows: coating a silica precursor solution on the surface of a glass substrate, and obtaining a glass substrate with silica gel attached to the surface after laser processing; placing the glass substrate with silica gel attached to the surface into a mixed solution of ethanol and water to obtain a glass substrate with a porous silica film attached to the surface; peeling off the porous silica film on the surface of the glass substrate to obtain a porous silica film; the raw materials of the silica precursor solution include sodium dodecyl sulfate, tetraethyl orthosilicate solution and hydrochloric acid solution, and calculated by volume ratio, the dodecyl sulfate solution is 1.0-1.0; the tetraethyl orthosilicate solution is 1.0-1.0; the tetraethyl orthosilicate solution is 1.0-1.0; the tetraethyl orthosilicate solution is 1.0-1.0; the tetraethyl orthosilicate solution is 1.0-1.0; the tetraethyl orthosilicate solution is 1.0-1.0; the tetraethyl orthosilicate solution is 1.0-1.0 The mixing ratio of alkyl sodium sulfate, tetraethyl orthosilicate solution and hydrochloric acid solution is 0.3:1:0.005; the concentration of hydrochloric acid in the hydrochloric acid solution is 0.01-0.03 mol / L; the raw materials of the tetraethyl orthosilicate solution include tetraethyl orthosilicate, anhydrous ethanol and water, and the mixing ratio of tetraethyl orthosilicate, anhydrous ethanol and water is 1:3:8 according to the molar ratio; the specific method of carboxylation treatment is: laser processing the porous silica film to obtain a porous silica film with increased surface activity; coating the carboxylation precursor solution on the surface of the porous silica film with increased surface activity, and heating it at 60°C for 0.5°C to obtain a carboxylation-treated porous silica film; wherein, according to the volume ratio, the mixing ratio of chloroacetic acid and water in the carboxylation precursor solution is 1:8;

[0112] B. dissolving anhydrous ferric chloride in water and stirring to obtain a ferric chloride solution; immersing the porous silica film with carboxyl groups on the surface in step A in the ferric chloride solution, taking it out and heating it at 60° C. to obtain a porous silica film with ferric chloride hexahydrate attached to the surface; the mixing ratio of anhydrous ferric chloride to water is 1:4 according to the mass ratio;

[0113] C. The porous silica film with ferric chloride hexahydrate attached to the surface in step B is laser processed by using a laser with a wavelength of 360 nm and a power of 15 W to obtain a porous silica film with a silicon dioxide-ferroferric oxide precursor attached to the surface;

[0114] D. Stripping the silica-ferroferric oxide precursor on the surface of the porous silica film in step C to obtain a silica-ferroferric oxide precursor; ultrasonically oscillating the silica-ferroferric oxide precursor in an ultrasonic oscillator with an oscillation frequency of 30 kHz for 5 minutes to obtain silica-ferroferric oxide magnetic particles.

[0115] The silicon dioxide-iron tetroxide magnetic particles obtained in Example 2 are dispersed in a polyvinyl pyrrolidone solution containing 3wt% polyvinyl pyrrolidone, and a rotating magnetic field is applied to magnetize to obtain a magnetically driven cluster micro-nano robot. The magnetically driven cluster micro-nano robot is immersed in a doxorubicin solution with a concentration of 50-60μg / ml, and taken out after standing for 2 hours to obtain a magnetically driven cluster micro-nano robot loaded with doxorubicin; the magnetically driven cluster micro-nano robot is driven in a rotating magnetic field with an intensity of 8mT to target the affected area for recruitment. The concentration of the doxorubicin solution after the magnetically driven cluster micro-nano robot is immersed is measured by a fluorescence spectrophotometer, so as to calculate the drug loading rate of the magnetically driven cluster micro-nano robot, and the motion trajectory of the magnetically driven cluster micro-nano robot is observed under a microscope.

[0116] The experimental results show that the drug loading rate of the magnetically driven cluster micro-nano robot prepared in Example 2 is 83%, which can accurately target the lesion area under the guidance of the rotating magnetic field to achieve precise positioning and delivery of doxorubicin. The drug loading performance of the magnetically driven cluster micro-nano robot is directly related to the adsorption force of the silica-iron tetroxide magnetic particles, which is specifically manifested as follows: the adsorption force of the silica-iron tetroxide magnetic particles is enhanced, and the drug loading capacity of the magnetically driven cluster micro-nano robot constructed on the basis of the silica-iron tetroxide magnetic particles is also improved. In addition, the positioning accuracy of the magnetically driven cluster micro-nano robot is closely related to the suspension stability of the silica-iron tetroxide magnetic particles; the higher the suspension stability of the silica-iron tetroxide magnetic particles, the more accurate the positioning of the prepared magnetically driven cluster micro-nano robot. The performance of the magnetically driven cluster micro-nano robot shown in Example 2 verifies that the silica-iron tetroxide magnetic particles in this technical solution have excellent suspension stability and strong adsorption capacity.

[0117] Example 3

[0118] A. Prepare a porous silica film; perform an amination treatment on the porous silica film to obtain a porous silica film with amino groups on the surface; wherein the amino groups are used to combine with drug molecules and to form charged groups in the solution; the method for preparing the porous silica film is specifically as follows: apply a silica precursor solution on the surface of a glass substrate, and obtain a glass substrate with silica gel attached to the surface after laser processing; place the glass substrate with silica gel attached to the surface into a mixed solution of ethanol and water to obtain a glass substrate with a porous silica film attached to the surface; peel off the porous silica film on the surface of the glass substrate to obtain a porous silica film; the raw materials of the silica precursor solution include hexadecyltrimethylammonium bromide, tetraethyl orthosilicate solution and hydrochloric acid solution, and the mixing ratio of hexadecyltrimethylammonium bromide, tetraethyl orthosilicate solution and hydrochloric acid solution is 0.2:1:0.003 according to the volume ratio; the hydrochloric acid The concentration of hydrochloric acid in the solution is 0.03 mol / L; the raw materials of the tetraethyl orthosilicate solution include tetraethyl orthosilicate, anhydrous ethanol and water, and the mixing ratio of tetraethyl orthosilicate, anhydrous ethanol and water is 1:4:9 according to the molar ratio; the specific method of the amination treatment is: laser processing the porous silica film to obtain a porous silica film with increased surface activity; coating the amination precursor solution on the surface of the porous silica film with increased surface activity, and heating it at 58°C for 0.55h to obtain an amination-treated porous silica film; wherein, according to the volume ratio, the mixing ratio of 3-aminopropyltriethoxysilane solution and acetic acid solution in the amination precursor solution is 1:0.05; according to the molar ratio, the mixing ratio of 3-aminopropyltriethoxysilane, anhydrous ethanol and water in the 3-aminopropyltriethoxysilane solution is 1:11:10; the concentration of acetic acid in the acetic acid solution is 0.02 mol / L;

[0119] B. dissolving anhydrous ferric chloride in water and stirring to obtain a ferric chloride solution; immersing the porous silica film with carboxyl groups on the surface in step A in the ferric chloride solution, taking it out and heating it at 70° C. to obtain a porous silica film with ferric chloride hexahydrate attached to the surface; the mixing ratio of anhydrous ferric chloride to water is 1:4 according to the mass ratio;

[0120] C. The porous silica film with ferric chloride hexahydrate attached to the surface in step B is laser processed by using a laser with a wavelength of 350 nm and a power of 10 W to obtain a porous silica film with a silicon dioxide-ferroferric oxide precursor attached to the surface;

[0121] D. Stripping the silica-ferroferric oxide precursor on the surface of the porous silica film in step C to obtain a silica-ferroferric oxide precursor; ultrasonically oscillating the silica-ferroferric oxide precursor in an ultrasonic oscillator with an oscillation frequency of 40 kHz for 3 minutes to obtain silica-ferroferric oxide magnetic particles.

[0122] The silicon dioxide-iron tetroxide magnetic particles obtained in Example 3 are dispersed in a polyvinyl pyrrolidone solution containing 3wt% polyvinyl pyrrolidone, and a rotating magnetic field is applied to magnetize to obtain a magnetically driven cluster micro-nano robot. The magnetically driven cluster micro-nano robot is immersed in a doxorubicin solution with a concentration of 50-60μg / ml, and taken out after standing for 2 hours to obtain a magnetically driven cluster micro-nano robot loaded with doxorubicin; the magnetically driven cluster micro-nano robot is driven in a rotating magnetic field with an intensity of 8mT to target the affected area for recruitment. The concentration of the doxorubicin solution after the magnetically driven cluster micro-nano robot is immersed is measured by a fluorescence spectrophotometer, so as to calculate the drug loading rate of the magnetically driven cluster micro-nano robot, and the motion trajectory of the magnetically driven cluster micro-nano robot is observed under a microscope.

[0123] The experimental results show that the drug loading rate of the magnetically driven cluster micro-nano robot prepared in Example 3 is 81%, which can accurately target the lesion area under the guidance of the rotating magnetic field to achieve the precise positioning and delivery of doxorubicin. The drug loading performance of the magnetically driven cluster micro-nano robot is directly related to the adsorption force of the silica-iron tetroxide magnetic particles, which is specifically manifested as follows: the adsorption force of the silica-iron tetroxide magnetic particles is enhanced, and the drug loading capacity of the magnetically driven cluster micro-nano robot constructed on the basis of the silica-iron tetroxide magnetic particles is also improved. In addition, the positioning accuracy of the magnetically driven cluster micro-nano robot is closely related to the suspension stability of the silica-iron tetroxide magnetic particles; the higher the suspension stability of the silica-iron tetroxide magnetic particles, the more accurate the positioning of the prepared magnetically driven cluster micro-nano robot. The performance of the magnetically driven cluster micro-nano robot shown in Example 3 verifies that the silica-iron tetroxide magnetic particles in this technical solution have excellent suspension stability and strong adsorption capacity.

[0124] Comparative Example 1

[0125] The preparation method and raw materials used in Comparative Example 1 are the same as those in the examples, except that a silicon dioxide film is used in place of a porous silicon dioxide film in Comparative Example 1. That is, the preparation method of the silica film in Comparative Example 1 is specifically as follows: coating a silica precursor solution on the surface of a substrate, and obtaining a substrate with silica gel attached to the surface after laser processing; placing the substrate with silica gel attached to the surface into a mixed solution of ethanol and water to obtain a substrate with a silica film attached to the surface; peeling off the silica film on the surface of the substrate to obtain a silica film; wherein, the raw materials of the silica precursor solution include tetraethyl orthosilicate solution and hydrochloric acid solution, and calculated by volume ratio, the mixing ratio of tetraethyl orthosilicate solution and hydrochloric acid solution is (0.1~0.3):1:(0.001~0.005); the raw materials of the tetraethyl orthosilicate solution include tetraethyl orthosilicate, anhydrous ethanol and water, and calculated by molar ratio, the mixing ratio of tetraethyl orthosilicate, anhydrous ethanol and the water is 1:(2~6):(8~12).

[0126] The silicon dioxide-iron tetroxide magnetic particles obtained in Comparative Example 1 are dispersed in a polyvinyl pyrrolidone solution containing 3wt% polyvinyl pyrrolidone, and a rotating magnetic field is applied to magnetize to obtain a magnetically driven cluster micro-nano robot. The magnetically driven cluster micro-nano robot is immersed in a doxorubicin solution with a concentration of 50-60μg / ml, and taken out after standing for 2 hours to obtain a magnetically driven cluster micro-nano robot loaded with doxorubicin; the magnetically driven cluster micro-nano robot is driven in a rotating magnetic field with an intensity of 8mT to target the affected area for recruitment. The concentration of the doxorubicin solution after the magnetically driven cluster micro-nano robot is immersed is measured by a fluorescence spectrophotometer, so as to calculate the drug loading rate of the magnetically driven cluster micro-nano robot, and the motion trajectory of the magnetically driven cluster micro-nano robot is observed under a microscope.

[0127] The experimental results show that the drug loading rate of the magnetically driven cluster micro-nano robot prepared in Comparative Example 1 is only 43%, which cannot meet the drug loading requirements, and cannot accurately target the lesion area under the guidance of the rotating magnetic field, and cannot achieve accurate positioning and delivery of doxorubicin. This is because the silica film in Comparative Example 1 has no porous structure, which affects its suspension stability and adsorption capacity, resulting in a decrease in the positioning accuracy and drug loading capacity of the magnetically driven cluster micro-nano robot obtained by magnetizing the silica-ferroferric oxide magnetic particles under the action of a magnetic field.

[0128] Comparative Example 2

[0129] The preparation method and the raw materials used in Comparative Example 2 are the same as those in Example 1, except that the porous silicon dioxide film is not subjected to an amination treatment in Comparative Example 2.

[0130] The silicon dioxide-iron tetroxide magnetic particles obtained in Comparative Example 2 are dispersed in a polyvinyl pyrrolidone solution containing 3wt% polyvinyl pyrrolidone, and a rotating magnetic field is applied to magnetize to obtain a magnetically driven cluster micro-nano robot. The magnetically driven cluster micro-nano robot is immersed in a doxorubicin solution with a concentration of 50-60μg / ml, and taken out after standing for 2 hours to obtain a magnetically driven cluster micro-nano robot loaded with doxorubicin; the magnetically driven cluster micro-nano robot is driven in a rotating magnetic field with an intensity of 8mT to target the affected area for recruitment. The concentration of the doxorubicin solution after the magnetically driven cluster micro-nano robot is immersed is measured by a fluorescence spectrophotometer, so as to calculate the drug loading rate of the magnetically driven cluster micro-nano robot, and the motion trajectory of the magnetically driven cluster micro-nano robot is observed under a microscope.

[0131] The experimental results show that the drug loading rate of the magnetically driven cluster micro-nano robot prepared in Comparative Example 2 is only 65%, which cannot meet the drug loading requirements, and cannot accurately target the lesion area under the guidance of the rotating magnetic field, and cannot achieve accurate positioning and delivery of doxorubicin. This is because the porous silica film was not aminated in Comparative Example 2, which affected its suspension stability and adsorption capacity, resulting in a decrease in the positioning accuracy and drug loading capacity of the magnetically driven cluster micro-nano robot obtained by magnetizing the silica-ferroferric oxide magnetic particles under the action of a magnetic field.

[0132] The technical principle of the present invention is described above in conjunction with specific embodiments. These descriptions are only for explaining the principle of the present invention and cannot be interpreted as limiting the scope of protection of the present invention in any way. Based on the explanations herein, those skilled in the art can associate other specific implementations of the present invention without paying creative labor, and these methods will fall within the scope of protection of the present invention.

Claims

1. A method for preparing silicon dioxide-ferroferric oxide magnetic particles, characterized in that: The following steps are involved: A. preparing a porous silica film; performing functional treatment on the porous silica film to obtain a porous silica film with functional groups on the surface; wherein the functional groups are used to bind to drug molecules and to form charged groups in the solution; B. dissolving anhydrous ferric chloride in water and stirring to obtain a ferric chloride solution; immersing the porous silica film with functional groups on the surface in step A in the ferric chloride solution, taking it out and heating it to obtain a porous silica film with ferric chloride hexahydrate attached to the surface; C. laser processing the porous silica film with ferric chloride hexahydrate attached to the surface in step B to obtain a porous silica film with a silica-ferroferric oxide precursor attached to the surface; D. peeling off the silica-ferroferric oxide precursor on the surface of the porous silica film in step C to obtain a silica-ferroferric oxide precursor; ultrasonically vibrating the silica-ferroferric oxide precursor to obtain silica-ferroferric oxide magnetic particles.

2. The method for preparing silicon dioxide-ferroferric oxide magnetic particles according to claim 1, characterized in that: In step A, the preparation method of the porous silicon dioxide film is specifically as follows: The silica precursor solution is coated on the surface of the substrate, and the substrate with silica gel attached to the surface is obtained after laser processing; The substrate with the silica gel attached to the surface is placed in a mixed solution of ethanol and water to obtain a substrate with a porous silica film attached to the surface; The porous silicon dioxide film is peeled off from the surface of the substrate to obtain a porous silicon dioxide film; The raw materials of the silicon dioxide precursor solution include a template, a tetraethyl orthosilicate solution and a hydrochloric acid solution, and the mixing ratio of the template, the tetraethyl orthosilicate solution and the hydrochloric acid solution is (0.1-0.3):1:(0.001-0.005) calculated by volume ratio; The raw materials of the tetraethyl orthosilicate solution include tetraethyl orthosilicate, anhydrous ethanol and water, and calculated by molar ratio, the mixing ratio of the tetraethyl orthosilicate, the anhydrous ethanol and the water is 1:(2-6):(8-12).

3. The method for preparing silicon dioxide-ferroferric oxide magnetic particles according to claim 1, characterized in that: In step A, the functionalization treatment is an amination treatment or a carboxylation treatment; The functional group includes any one of an amino group and a carboxyl group.

4. The method for preparing silicon dioxide-ferroferric oxide magnetic particles according to claim 3, characterized in that: The specific method of the amination treatment is: laser processing the porous silica film to obtain a porous silica film with increased surface activity; coating the amination precursor solution on the surface of the porous silica film with increased surface activity, and heating at 50 to 60° C. for 0.5 to 0.6 h to obtain the amination-treated porous silica film; The raw materials of the amination precursor solution include 3-aminopropyltriethoxysilane solution and acetic acid solution; the raw materials of the 3-aminopropyltriethoxysilane solution include 3-aminopropyltriethoxysilane, anhydrous ethanol and water.

5. The method for preparing silicon dioxide-ferroferric oxide magnetic particles according to claim 3, characterized in that: The specific method of the carboxylation treatment is: laser processing the porous silica film to obtain a porous silica film with increased surface activity; coating the carboxylation precursor solution on the surface of the porous silica film with increased surface activity, heating it at 50 to 60° C. for 0.5 to 0.6° C. to obtain a carboxylation-treated porous silica film; Wherein, the raw materials of the carboxylation precursor solution include chloroacetic acid and water.

6. The method for preparing silicon dioxide-ferroferric oxide magnetic particles according to claim 1, characterized in that: In step B, the mixing ratio of the anhydrous ferric chloride to the water is 1:(2-4) calculated by mass ratio; In step B, the heating temperature is 60-80°C.

7. The method for preparing silicon dioxide-ferroferric oxide magnetic particles according to claim 1, characterized in that: In step C, the laser wavelength of the laser processing is 350-360nm, and the laser power is 10-15W.

8. The method for preparing silicon dioxide-ferroferric oxide magnetic particles according to claim 1, characterized in that: In step D, the ultrasonic oscillation time is 3 to 5 minutes and the frequency is 30 to 40 kHz.

9. A silicon dioxide-iron tetroxide magnetic particle, characterized in that: The magnetic particles are prepared by the method for preparing silicon dioxide-ferroferric oxide magnetic particles according to any one of claims 1 to 8.

10. An application of silicon dioxide-iron tetroxide magnetic particles in the preparation of magnetically driven cluster micro-nano robots, characterized in that: Using the silicon dioxide-iron tetroxide magnetic particles as described in claim 9, the application method is: putting the silicon dioxide-iron tetroxide magnetic particles into a polyvinyl pyrrolidone solution for dispersion, and applying a rotating magnetic field to magnetize to obtain a magnetically driven cluster micro-nano robot; Wherein, calculated by mass percentage, the content of polyvinyl pyrrolidone in the polyvinyl pyrrolidone solution is 2-5%; The shape of the magnetically driven cluster micro-nano robot is circular or elliptical, and the drug loading rate is 80-85%.