Preparation method and application of a mesoporous silica lipoprotein complex drug delivery system based on electrostatic stabilization
By preparing a mesoporous silica lipoprotein complex drug delivery system, the problems of poor water solubility and insufficient targeting of anticancer drugs were solved, achieving efficient killing of cancer cells and low toxicity to normal cells, and demonstrating good therapeutic effects.
Patent Information
- Application Number
- CN202310142020.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-02-21
- Publication Date
- 2025-09-26
- Estimated Expiration
- 2043-02-21
AI Technical Summary
Existing anticancer drugs such as docetaxel have poor water solubility and poor targeting, which limits their therapeutic effects. At the same time, the high concentration and poor biocompatibility of HAMLET restrict its clinical application, and there is a lack of effective methods to selectively kill tumor cells.
By preparing a mesoporous silica lipoprotein complex drug delivery system based on electrostatic interaction, the hydrophobic anticancer drug docetaxel was loaded onto amino-modified mesoporous silica nanoparticles, and BAMLET formed by α-lactalbumin and oleic acid was wrapped on the surface of the nanoparticles to form a stable mesoporous silica lipoprotein complex BMSN/DTX.
It achieves highly efficient killing effects on a variety of cancer cells, has low toxicity to normal differentiated cells, shows good therapeutic effects in combination with chemotherapy-immunotherapy, and simplifies the preparation process.
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Figure CN116059185B_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of nano drug delivery systems for anticancer treatment, and in particular relates to a preparation method and application of a mesoporous silica lipoprotein complex drug delivery system based on electrostatic stabilization. Background Art
[0002] Currently, traditional treatments, such as surgical resection, chemotherapy or radiotherapy, are still the first-line methods for cancer treatment, but poor targeting, severe side effects and multidrug resistance limit their efficacy. For example, docetaxel (DTX) is a first-line anticancer drug for the treatment of breast cancer and lung cancer, but its poor water solubility may hinder its clinical application.
[0003] HAMLET or BAMLET (human / bovine α-lactalbumin lethal to tumor cells) is a well-known anticancer drug, a lipoprotein complex. Since its initial discovery in breast milk in 1995, HAMLET has been extensively studied. It is capable of killing a variety of cancer cells while exhibiting negligible cytotoxicity against normal cells. However, BAMLET's high concentrations, reaching mg / ml, are labor-intensive and have hindered its practical application. Furthermore, due to BAMLET's poor biocompatibility and potent hemolytic activity, it has not yet been tested for therapeutic use via intravascular administration.
[0004] Therefore, there is an urgent need to develop new treatment modalities to selectively kill tumor cells while causing minimal damage to healthy tissues while achieving satisfactory therapeutic effects. Summary of the Invention
[0005] To address the aforementioned problems with the prior art, the first objective of the present invention is to provide a method for preparing a drug-delivery system based on electrostatically stabilized mesoporous silica sphere-lipoprotein complexes. The resulting material exhibits a potent killing effect on various cancer cells and is non-toxic to normally differentiated cells. Furthermore, the therapeutic efficacy of chemo-immunotherapy has been demonstrated in animals. A second objective of the present invention is to provide a composite material obtained using the aforementioned method. A third objective is to provide uses for the composite material.
[0006] The technical solution adopted by the present invention to solve the technical problem is:
[0007] In a first aspect, the present invention provides a method for preparing a drug delivery system of a mesoporous silica lipoprotein complex stabilized by electrostatic interaction, comprising the following steps:
[0008] In the first step, the anticancer drug is uniformly dispersed in dichloromethane, and then the amino-modified mesoporous silica nanoparticles are added, stirred at the reaction temperature, and dried to obtain the mesoporous silica nanoparticles loaded with the anticancer drug;
[0009] In the second step, the anticancer drug-loaded mesoporous silica nanoparticles are ultrasonically dispersed in a phosphate buffer solution, α-lactalbumin is added, and the solution is incubated.
[0010] In the third step, after the incubation is completed, oleic acid is added and reacted under the reaction conditions; after the reaction, freeze-drying is performed to obtain a lipoprotein-encapsulated mesoporous silica-loaded anticancer drug composite material.
[0011] Among them, the complex formed by α-lactalbumin and oleic acid is BAMLET.
[0012] Mesoporous silica nanoparticles (MSNs) have a regular mesostructure, high surface area, and large pore volume, and are excellent carriers for hydrophobic drug delivery. The present invention combines BAMLET with drug-loaded nanocarriers to improve the anti-cancer effect.
[0013] In an embodiment of the method of the present invention, the anticancer drug is a hydrophobic anticancer drug, such as docetaxel DTX.
[0014] In the embodiment of the method of the present invention, the amino-modified mesoporous silica can be purchased commercially or prepared by oneself.
[0015] The surface of amino-modified mesoporous silica (MSN-NH2) is positively charged, and the surface of BAMLET is negatively charged. Docetaxel is loaded in the pores of the silica spheres, and BAMLET is coated on the outside of the docetaxel-loaded silica spheres by electrostatic attraction to synthesize a mesoporous silica sphere-coupled lipoprotein complex drug delivery system (BMSN / DTX).
[0016] In an embodiment of the method of the present invention, in the first step, the mass volume ratio of the amino-modified mesoporous silica nanoparticles to dichloromethane is: 0.025±0.001g:10±1ml, for example, it can be 0.025±0.001g:10ml, 0.025±0.001g:9ml, 0.025±0.001g:11ml, etc.
[0017] Preferably, the mass ratio of the amino-modified mesoporous silica nanoparticles to docetaxel is 0.025±0.001 g:0.025±0.001 g.
[0018] In a specific embodiment of the present invention, in the first step, the hydrophobic anticancer drug is first dissolved in dichloromethane, and then amino-modified mesoporous silica nanoparticles are added and ultrasonically dispersed; the reaction conditions of the first step are: reaction temperature 25±5°C, reaction time at least 24 hours, continuous stirring during the reaction, and collection of the precipitate by ultracentrifugation after the reaction; washing conditions are: washing with deionized water; and freeze drying to obtain a solid.
[0019] Preferably, the reaction time is at least 24 hours, for example, 24 hours, 25 hours, 26 hours, 27 hours, 28 hours, 29 hours, 30 hours, 35 hours, 40 hours, 45 hours, 48 hours, etc. A longer reaction time is beneficial to the loading of anticancer drugs on mesoporous silica nanoparticles.
[0020] In a specific embodiment of the present invention, in the second step, the mass volume ratio of the mesoporous silica nanoparticles loaded with anticancer drugs to the phosphate buffer is: 0.01±0.001g:1.43±0.001ml; the mass ratio of the mesoporous silica nanoparticles loaded with anticancer drugs to α-lactalbumin is 5mg:2.5-10mg, such as 5mg:2.5mg, 5mg:5mg, 5mg:10mg; the pH of the PBS buffer is: 8±1; the reaction conditions of the second step are: reaction temperature 25±5°C, and reaction time of at least 20min.
[0021] Preferably, in the third step, the molar ratio of oleic acid to α-lactalbumin is 1:20 to 40, such as 1:20, 1:30, or 1:40; the reaction conditions are: reaction temperature of 45±10°C, reaction time of 15 min; ultracentrifugation is used to collect the precipitate; and freeze-drying is used to obtain the solid.
[0022] In a second aspect, the present invention also protects the composite material obtained by the preparation method described above.
[0023] In a third aspect, the present invention also protects the use of the composite material described above in the preparation of anticancer drugs.
[0024] Beneficial effects
[0025] Compared with the existing technology, the mesoporous silica sphere-coupled lipoprotein complex drug delivery system obtained in the present invention has broad-spectrum anti-cancer properties and low toxicity to normal differentiated and mature normal cells; animal tumor model experiments have shown that the composite material combined with immunotherapy has a good therapeutic effect.
[0026] The preparation method of the present invention involves loading amino-modified mesoporous silica nanoparticles with a hydrophobic anticancer drug, then adsorbing and coating the surface of the material with α-lactalbumin. Finally, oleic acid is added to form a BAMLET complex, which is then coated on the surface of the silica spheres to produce the finished composite material. This method is concise and easy to operate, combining the anticancer drug activity with the tumor-killing effect of BAMLET in a single step. BRIEF DESCRIPTION OF THE DRAWINGS
[0027] Figure 1 Schematic diagram of the reaction principle of Examples 1, 2, and 3 of the present invention.
[0028] Figure 2Figure 3 shows the morphological characteristics of the nanomaterials obtained in Example 3. Transmission electron microscopy images of MSN-NH2 (A, B) and BMSN / DTX (E, F). The insets show the size distribution of MSN-NH2 and BMSN / DTX. Scanning electron microscopy images of MSN-NH2 (C, D) and BMSN / DTX (G, H).
[0029] Figure 3 Figure 1 shows the physical and chemical characterization of the nanoparticles obtained in Examples 1, 2, and 3 of the present invention. (A) Infrared spectra of the silica composite. (B) Thermogravimetric curves of MSN-NH2, MSN-NH2 / DTX, and BMSN / DTX. (C) UV-visible spectra of BLA, BAMLET, MSN-NH2, and BMSN. (D) SDS-PAGE gel analysis of the samples using Coomassie Brilliant Blue staining. (E) Zeta potential of the nanoparticles. (F) DTX release curves of BMSN / DTX at pH 5.5 and 7.4.
[0030] Figure 4 This is the confocal fluorescence imaging of the uptake of BMSN / DTX nanoparticles by HeLa cells in Example 3 of the present invention.
[0031] Figure 5 The relative viability of cancer cells after different types of cancer cells were treated with different concentrations of the materials in Example 3 of the present invention for 24 hours.
[0032] Figure 6 The relative viability of normal differentiated and mature cells after being treated with the materials of Example 3 of the present invention at different concentrations for 24 hours.
[0033] Figure 7 The therapeutic effects of combined chemotherapy and immunotherapy on tumor-bearing mice in Example 3 of the present invention are shown. (A) Tumor volume of tumor-bearing mice after treatment with different methods. (B) Body weight changes of different groups. DETAILED DESCRIPTION
[0034] The present invention is further described in detail below with reference to the examples. Reagents or instruments used without manufacturer's indication are considered to be conventional products that can be purchased on the market.
[0035] The basic preparation process of this embodiment includes:
[0036] The first step is to uniformly disperse the anticancer drug in dichloromethane, then add the amino-modified mesoporous silica nanoparticles, stir at the reaction temperature, and dry to obtain the anticancer drug-loaded mesoporous silica nanoparticles;
[0037] The second step is to uniformly disperse the mesoporous silica nanoparticles loaded with anticancer drugs in a phosphate buffer solution by ultrasonication, add α-lactalbumin thereto, and incubate the solution;
[0038] Step 3: After the incubation is completed, oleic acid is added and reacted under the reaction conditions; after the reaction, freeze-drying is performed to obtain a finished product of the lipoprotein-encapsulated mesoporous silica loaded anticancer drug composite material.
[0039] Specifically, in the first step, the anticancer drug is paclitaxel; the mass volume ratio of the amino-modified mesoporous silica nanoparticles to dichloromethane is: 0.025±0.001g:10±1ml; the mass ratio of the amino-modified mesoporous silica nanoparticles to the anticancer drug docetaxel is 0.025±0.001g:0.025±0.001g; in the first step, the hydrophobic anticancer drug is first dissolved in dichloromethane, and then the mesoporous silica nanoparticles are added and ultrasonically dispersed; the reaction conditions for the first step are: reaction temperature 25±5°C, reaction time at least 24 hours, and continuous stirring during the reaction; the precipitate is collected by ultracentrifugation; the washing conditions are: washing three times with deionized water; and freeze-drying is used to obtain a solid;
[0040] In the second step, the mass volume ratio of mesoporous silica nanoparticles loaded with anticancer drugs and phosphate buffer is: 0.01±0.001g:1.43±0.001ml; the mass ratio of mesoporous silica nanoparticles loaded with anticancer drugs and α-lactalbumin is 5mg:2.5~10mg; the pH of PBS buffer is: 8±1; the reaction conditions of the second step are: reaction temperature 25±5℃, reaction time at least 20min.
[0041] By adopting the above preferred solution, the key material ratios and specific conditions in the second step can be further optimized. Among them, the phosphate buffer solution is PBS.
[0042] In the third step, the molar ratio of oleic acid to α-lactalbumin is 30:1; the reaction conditions are: reaction temperature is 45±10°C, reaction time is 15 minutes; the precipitate is collected by ultracentrifugation; and the solid is obtained by freeze drying.
[0043] Preferred embodiments of the present invention are described below by way of example, but the present invention is not limited thereto.
[0044] Example 1 Preparation of Mesoporous Silica Sphere-Coupled Lipoprotein Complex Drug Delivery System
[0045] (1) 25 mg of docetaxel was weighed and dissolved in 10 ml of dichloromethane. 25 mg of amino-modified mesoporous silica nanoparticles were added and ultrasonically dispersed. The mixture was stirred in a sealed container at 25°C for 24 h. The resulting solid was washed three times with deionized water and centrifuged at 10,000 rpm for 10 min. After freeze-drying, the drug-loaded mesoporous silica material was obtained, designated MSN-NH2 / DTX.
[0046] (2) Weigh 5 mg of MSN-NH2 / DTX and ultrasonically disperse it in a PBS buffer solution with a pH of 8. Add 2.5 mg of α-lactalbumin, vortex for 30 seconds, and incubate at 25°C for 20 minutes.
[0047] (3) After the reaction is complete, oleic acid is added to adjust the molar ratio of α-lactalbumin to oleic acid to 1:30. Vortex mix three times for 10 seconds each time, react at 45°C for 15 minutes, and centrifuge at 10,000 rpm for 10 minutes. After freeze-drying, the drug-loaded mesoporous silica sphere-coupled lipoprotein complex is obtained, which is designated as BMSN 1:0.5.
[0048] Example 2 Preparation of Mesoporous Silica Sphere-Coupled Lipoprotein Complex Drug Delivery System
[0049] (1) 25 mg of docetaxel was weighed and dissolved in 10 ml of dichloromethane. 25 mg of amino-modified mesoporous silica nanoparticles were added and ultrasonically dispersed. The mixture was stirred in a sealed container at 25°C for 24 h. The resulting solid was washed three times with deionized water and centrifuged at 10,000 rpm for 10 min. After freeze-drying, the drug-loaded mesoporous silica material was obtained, designated MSN-NH2 / DTX.
[0050] (2) Weigh 5 mg of MSN-NH2 / DTX and ultrasonically disperse it in a PBS buffer solution with a pH of 8. Add 5 mg of α-lactalbumin, vortex for 30 seconds, and incubate at 25°C for 20 minutes.
[0051] (3) After the reaction is complete, oleic acid is added to adjust the molar ratio of α-lactalbumin to oleic acid to 1:30. Vortex mix three times for 10 seconds each time, react at 45°C for 15 minutes, and centrifuge at 10,000 rpm for 10 minutes. After freeze-drying, the drug-loaded mesoporous silica sphere-coupled lipoprotein complex is obtained, which is designated as BMSN 1:1.
[0052] Example 3 Preparation of Mesoporous Silica Sphere-Coupled Lipoprotein Complex Drug Delivery System
[0053] (1) 25 mg of docetaxel was weighed and dissolved in 10 ml of dichloromethane. 25 mg of amino-modified mesoporous silica nanoparticles were added and ultrasonically dispersed. The mixture was stirred in a sealed container at 25°C for 24 h. The resulting solid was washed three times with deionized water and centrifuged at 10,000 rpm for 10 min. After freeze-drying, the drug-loaded mesoporous silica material was obtained, designated MSN-NH2 / DTX.
[0054] (2) Weigh 5 mg of MSN-NH2 / DTX and ultrasonically disperse it in a PBS buffer solution with a pH of 8. Add 10 mg of α-lactalbumin, vortex for 30 seconds, and incubate at 25°C for 20 minutes.
[0055] (3) After the reaction is complete, oleic acid is added to adjust the molar ratio of α-lactalbumin to oleic acid to 1:30. Vortex mix three times for 10 seconds each, react at 45°C for 15 minutes, and centrifuge at 10,000 rpm for 10 minutes. After freeze-drying, the drug-loaded mesoporous silica sphere-coupled lipoprotein complex is obtained, designated as BMSN1:2.
[0056] Comparative Example 1 Preparation of BAMLET lipoprotein anticancer complex
[0057] (1) Weigh 28.3 mg of α-lactalbumin and dissolve it in 2 ml of PBS buffer solution at pH 8 to make the final concentration of α-lactalbumin 1 mM.
[0058] (2) Oleic acid molecules were added to adjust the molar ratio of α-lactalbumin to oleic acid to 1:30. After sonication for 10 seconds, vortex mixing was performed three times for 10 seconds each, and the mixture was reacted at 45°C for 15 minutes to self-assemble into BAMLET.
[0059] (3) After the reaction is completed, BAMLET and excess free oleic acid are separated using a 30k ultrafiltration tube. The BAMLET lipoprotein anticancer complex is obtained after freeze-drying.
[0060] In this example, the BAMLET lipoprotein anticancer complex prepared in Example 1 was used to characterize its morphology using transmission electron microscopy (TEM).
[0061] Performance Testing
[0062] 1. The mesoporous silica sphere-coupled lipoprotein complex drug delivery system (BMSN / DTX) prepared in Example 3 was subjected to multiple tests, including transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), UV-visible spectroscopy, SDS-PAGE gel, zeta potential, and in vitro release curve.
[0063] The following are the results of testing the BMSN / DTX prepared in Example 3.
[0064] Figure 2 The middle image shows transmission electron microscopy (TEM) and scanning electron microscopy (SEM) images of MSN-NH2 and BMSN / DTX, with the insets showing the size distribution of MSN-NH2 and BMSN / DTX. The images show the distinct spherical silica composites, and the nanomaterials are monodispersed.
[0065] Figure 3 The physical and chemical characterization of the nanoparticles obtained in Example 3 of the present invention was performed. The spectra of the samples were recorded by Fourier transform infrared spectroscopy (FT-IR) to verify the synthesis of the composite material. -1 The broad peaks at 800, 462 cm-1 correspond to Si-O asymmetric stretching. -1 The broad peaks at about 2922 cm-1 are attributed to Si-O symmetric stretching and Si-O-Si asymmetric stretching vibrations. -1 and 2856cm -1 The two peaks appearing at 1735 cm are the stretching vibrations of CH on the surface of amino-functionalized monodispersed two-nanometer silicon. In addition, the CO stretching vibration at 1735 cm -1 A new peak appeared at 14.0 kDa, confirming the presence of DTX in the mesopores. TGA analysis further evaluated DTX loading. The thermal curve of MSN-NH2 / DTX was heavier than that of OA-MSNs, primarily due to DTX degradation. SDS-PAGE analysis revealed a band at 14.0 kDa similar to that of α-lactalbumin. The release rate of BMSN / DTX reached over 90% at pH 5.5, but was much lower at pH 7.4.
[0066] In addition, the identification results of various properties of the mesoporous silica sphere-coupled lipoprotein complex drug delivery systems prepared in Examples 1, 2, and 3 were the same or substantially the same as the above results, and the conclusions drawn from the identification results were the same as the above conclusions.
[0067] 2. Experimental Methods: We used confocal laser scanning microscopy (CLSM) to perform fluorescence imaging of HeLa cancer cells. BMSN / DTX was labeled with fluorescein isothiocyanate (FITC), and cell nuclei were labeled with 4,6-diamidino-2-phenylindole (DAPI). Cells were co-cultured with the BMSN / DTX-FITC conjugate for 2, 4, and 24 hours.
[0068] Figure 4Confocal fluorescence imaging of HeLa cells uptake of BMSN / DTX nanoparticles in Example 3 of the present invention. With increasing incubation time, the FITC fluorescence signal in HeLa cells treated with BMSN / DTX increases. After 24 hours of culture, the vast majority of cells die and slough off due to increased BMSN / DTX uptake.
[0069] 3. Experimental Method: Cells were seeded in 96-well plates at a density of 4000 cells / well and cultured for 24 hours. The culture medium was removed and replaced with fresh culture medium containing different concentrations of the nanocomposite material. After 72 hours of culture, cell viability was measured using a CCK-8 test kit. Absorbance was measured at a wavelength of 450 nm using a microplate reader, with cells not treated with the material serving as a control.
[0070] The nanoparticles were tested for cytotoxicity in four different cell lines: human breast cancer cell lines MDA-MB-231 and MCF-7, mouse breast cancer cell line 4T1, and mouse embryonic fibroblasts (3T3). Compared to the empty vector MSN-NH2 (at concentrations up to 400 μg / ml), the nanoparticles showed no significant cytotoxicity against any of the cell lines. Figure 5 The relative viability of cancer cells after different types of cancer cells were treated with different concentrations of the materials in Example 3 of the present invention for 24 hours. Figure 6 The relative viability of normal differentiated, mature cells after 24 hours of treatment with different concentrations of the materials described in Example 3. Once BLAs are coated on MSN-NH2 to form BMSNs, they exhibit significant cytotoxicity against all cancer cells. Furthermore, the toxicity of BAMLET and BMSNs toward differentiated, mature cells (3T3) is much lower than that toward cancer cells.
[0071] 4. Experimental Methods: This study used female BALB / c mice (6 weeks, ~17g SPF mice). All mice were housed in a sterile animal room with a 12-h light-dark cycle, an ambient temperature of 21°C, and a relative humidity of 40-70%. All mice had free access to food and water. Animal experiments were approved by the school's animal ethics committee and conducted in accordance with ethical guidelines. 4T1 cells (1*10 6 , 50 μl PBS and 50 μl matrix gel) were subcutaneously transplanted into the back of mice and cultured continuously until the tumor volume reached ∼100 mm 3 Dynamic monitoring of tumor volume, calculated as (long diameter * short diameter 2 ) / 2. When the tumor volume reaches 100mm 3All mice were randomly assigned to five groups. PBS, BAMLET, DTX, MSN-NH2 / DTX, and BMSN / DTX were intravenously injected every three days. Tumor size was measured with a vernier caliper, and mouse body weight was recorded. At the end of the experiment, all mice were euthanized to obtain solid tumors and major organs.
[0072] Figure 7 The results show the therapeutic effect of chemotherapy in tumor-bearing mice treated with the chemotherapy described in Example 3 of the present invention. The results show that the BMSN / DTX group had the best therapeutic effect, followed by the MSN-NH2 / DTX drug delivery system group. There were no significant differences in body weight between the groups during treatment, and no abnormalities were observed in the animals during treatment.
[0073] The protection content of the present invention is not limited to the above embodiments. Without departing from the spirit and scope of the inventive concept, changes and advantages that can be thought of by those skilled in the art are included in the present invention and are protected by the appended claims.
Claims
1. A method for preparing a drug delivery system of mesoporous silica lipoprotein complexes stabilized by electrostatic interaction, characterized in that: The following steps are involved: In the first step, the anticancer drug is uniformly dispersed in dichloromethane, and then amino-modified mesoporous silica nanoparticles are added, stirred at the reaction temperature, and dried to obtain mesoporous silica nanoparticles loaded with the anticancer drug; In the second step, the anticancer drug-loaded mesoporous silica nanoparticles are ultrasonically dispersed in a phosphate buffer solution, α-lactalbumin is added, and the solution is incubated. In the third step, after the incubation is completed, oleic acid is added and reacted under the reaction conditions, whereby the oleic acid forms a BAMLET complex that is coated on the surface of the silica spheres. After the reaction, drying is performed to obtain the finished product of the lipoprotein-coated mesoporous silica-loaded anticancer drug composite material. Wherein, in the first step, the anticancer drug is docetaxel; In the third step, the molar ratio of α-lactalbumin to oleic acid is 1:30; In the second step, the pH of the phosphate buffer is: 8 ± 1; In the third step, after the reaction, the precipitate is collected by ultracentrifugation and then freeze-dried to obtain a finished product of the lipoprotein-encapsulated mesoporous silica-loaded anticancer drug composite material, wherein the centrifugal speed is 10,000 rpm for 10 minutes.
2. The method for preparing the mesoporous silica lipoprotein complex drug delivery system according to claim 1, characterized in that: In the first step, the mass volume ratio of the amino-modified mesoporous silica nanoparticles to dichloromethane is 0.025±0.001 g:10±1 ml.
3. The method for preparing the mesoporous silica lipoprotein complex drug delivery system according to claim 1, characterized in that: In the first step, the mass volume ratio of the amino-modified mesoporous silica nanoparticles to dichloromethane is 0.025±0.001 g:10 ml.
4. The method for preparing the mesoporous silica lipoprotein complex drug delivery system according to claim 2, characterized in that: The mass ratio of amino-modified mesoporous silica nanoparticles to docetaxel is 0.025±0.001 g:0.025±0.001 g.
5. The method for preparing the mesoporous silica lipoprotein complex drug delivery system according to claim 1, characterized in that: In the first step, the anticancer drug is dissolved in dichloromethane, and then mesoporous silica nanoparticles are added and ultrasonically dispersed. The reaction conditions for the first step are: reaction temperature 25±5°C, reaction time at least 24 hours, and continuous stirring during the reaction. The precipitate is collected by ultracentrifugation. The washing conditions are: washing with deionized water, and freeze-drying to obtain a solid.
6. The method for preparing the mesoporous silica lipoprotein complex drug delivery system according to claim 1, characterized in that: In the second step, the mass volume ratio of mesoporous silica nanoparticles loaded with anticancer drugs to phosphate buffer is: 0.01±0.001g: 1.43±0.001ml; the mass ratio of mesoporous silica nanoparticles loaded with anticancer drugs to α-lactalbumin is 5mg:2.5~10mg; the pH of the phosphate buffer is: 8±1; the reaction conditions of the second step are: reaction temperature 25±5℃, reaction time at least 20min.
7. The method for preparing the mesoporous silica lipoprotein complex drug delivery system according to claim 1, characterized in that: In the third step, the molar ratio of α-lactalbumin to oleic acid is 1:30; the reaction conditions are: reaction temperature is 45±10°C, reaction time is 15 minutes; the precipitate is collected by ultracentrifugation; and the solid is obtained by freeze drying.
8. The composite material obtained by the preparation method of the mesoporous silica lipoprotein complex drug delivery system according to any one of claims 1 to 7.
9. Use of the composite material according to claim 8 in the preparation of anti-breast cancer drugs.