Preparation method and application of multistage rocket structure nano material

Abstract

The invention discloses a preparation method and application of a multistage rocket structure nanometer material in the technical field of biomedical materials. Mesoporous silicon dioxide (MSNs) serves as a core, gemcitabine (GEM) is wrapped in the core, the outer layer of the core is coated with calcium carbonate to form a middle layer, halofuginone (HF) is loaded on the middle layer, and the outermost layer is connected with targeting molecules to form a core-shell structure; the nano material has pH and GSH dual responsiveness, calcium carbonate on the outer layer is disintegrated in a subacid environment with the pH being 6.2-6.5, and mesoporous silica (MSNs) on the inner layer is further disintegrated in a 10mM GSH environment; the synthesis method provided by the invention is simple and easy to operate, and the nanoparticles have the advantages of large specific surface area, uniform particle size, good biocompatibility and the like.

Description

TECHNICAL FIELD

[0001] The application relates to the technical field of biomedical materials, in particular to a preparation method and application of a multi-stage rocket structure nanomaterial. BACKGROUND

[0002] Pancreatic cancer is a highly lethal solid tumor. Due to the difficulty in early diagnosis, most patients are diagnosed at an advanced stage. Even a small part of patients diagnosed as locally resectable have a 5-year survival rate of less than 20%. After decades of efforts, the five-year survival rate is still less than 10%. The current challenges of pancreatic cancer chemotherapy include: (1) the tumor biological barrier hinders drug penetration and intracellularization, and the delivery efficiency is low; (2) drug inactivation reduces the efficiency of chemotherapy and produces drug resistance.

[0003] Fibrous connective tissue hyperplasia is the most important pathological feature of pancreatic cancer, which forms a dense matrix physical barrier around tumor cells, seriously hinders the delivery of chemotherapy drugs and immune cell infiltration, and causes tumor cells to have high resistance to chemotherapy, radiotherapy and immunotherapy. Pancreatic cancer matrix fibrosis occurs continuously, and the proportion of tumor matrix in tumor volume is as high as 90%. The highly fibrotic tumor matrix greatly increases the interstitial fluid pressure, greatly squeezes the intratumoral blood vessels, seriously weakens the killing effect of drugs and immune cells, and makes the intratumoral blood vessels under high hypoxia and acidification conditions, and the intratumoral angiogenesis is intensified, forming a vicious cycle.

[0004] Based on this, the application designs a preparation method and application of a multi-stage rocket structure nanomaterial to solve the above problems. SUMMARY

[0005] The purpose of the application is to provide a preparation method and application of a multi-stage rocket structure nanomaterial to solve the problems raised in the background.

[0006] To achieve the above purpose, the application provides the following technical scheme: a multi-stage rocket structure nanomaterial, taking mesoporous silica (MSN) as a core, loading gemcitabine (GEM) in the core, forming an intermediate layer by coating the core with calcium carbonate, loading halofuginone (HF) on the intermediate layer, and connecting a targeting molecule to the outermost layer to form a core-shell structure; the particle size of the mesoporous silica (MSN) is about 120nm, the specific surface area is 307.78m 2 / g, and the pore size is 13.01nm; the nanomaterial has pH and GSH dual responsiveness, the outer layer of calcium carbonate collapses in a slightly acidic environment with pH=6.2-6.5, and the inner layer of mesoporous silica (MSN) further collapses in a 10mM GSH environment.

[0007] As a further scheme of the present application, the raw materials for preparing the nanomaterials include triethylamine (TEA), cetyltrimethylammonium bromide (CTAB), sodium salicylate (Nasal), tetraethyl orthosilicate (TEOS), 1,2-bis(triethoxysilyl)ethane (BTES), ethanol, hydrochloric acid, methanol, calcium chloride, gemcitabine (GEM), halofuginone (HF), and a targeting molecule.

[0008] A preparation method of a multi-stage rocket structure nanomaterial with mesoporous silica as a core, comprising the following steps: Step one: synthesizing mesoporous silica (MSN) by a solvent template method; Step two: loading gemcitabine (GEM) through overnight stirring to make it adsorbed in the mesoporous silica (MSN) mesopore to obtain Si-G; Step three: obtaining Si-G@Ca by a gas diffusion method and an acid etching method; Step four: loading halofuginone (HF) to obtain Si-G@Ca-H; Step five: connecting a targeting molecule to obtain a final preparation, i.e., a multi-stage rocket structure nanomaterial with mesoporous silica as a core.

[0009] As a further scheme of the present application, the solvent template method in step one uses triethylamine as a weak base and a surfactant, forms a hydrogen bond network with water through the tertiary amine group, provides a basic microenvironment for the formation of cetyltrimethylammonium bromide (CTAB) micelles, and accelerates molecular movement and promotes system homogenization through heating at 80℃.

[0010] As a further scheme of the present application, cetyltrimethylammonium bromide (CTAB) and sodium salicylate (Nasal) are needed to be co-dissolved in step one, cetyltrimethylammonium bromide (CTAB) is used as a cationic surfactant to form rod-shaped micelles under alkaline conditions and constitute the framework of the mesoporous template; sodium salicylate (Nasal) is used as a co-template agent to adjust the micelles and stabilize the mesoporous wall through electrostatic interaction with the cations of cetyltrimethylammonium bromide (CTAB), and 80℃ continuous stirring for 2 hours ensures sufficient self-assembly of the micelles.

[0011] As a further scheme of the present application, tetraethyl orthosilicate (TEOS) and ethane (BTES) are needed to be added in step one, both of which undergo hydrolysis-polycondensation reaction under alkaline conditions, and the silanization is ensured to be complete by continuous reaction at 80℃ for 12 hours to obtain mesoporous silica (MSN).

[0012] As a further scheme of the present application, the mesoporous silica (MSNs) obtained initially needs to be dispersed in a 2M HCl / methanol solution, and stirred at 75 DEG C for 24 h to remove cetyltrimethylammonium bromide (CTAB), so as to finally obtain mesoporous silica (MSNs).

[0013] The application of the multi-stage rocket structure nanomaterial with mesoporous silica as the core: through the layer-by-layer encapsulation technology, it is applied to the step-by-step release of drugs in the tumor microenvironment, breakthrough of the dense stroma barrier of pancreatic cancer, improvement of the drug delivery efficiency, and great potential in the treatment of pancreatic cancer.

[0014] Compared with the prior art, the present application has the beneficial effects that: 1. The synthesis method involved in the present application is simple and easy to operate, and the nanoparticles have the advantages of large specific surface area, uniform particle size, good biocompatibility and the like.

[0015] 2. The nanoparticles synthesized in the present application have a multi-stage rocket structure, effectively break through the dense stroma barrier of pancreatic cancer, and improve the enrichment effect of drugs in tumor tissues.

[0016] 3. The nanoparticles synthesized in the present application have pH and GSH dual responsiveness, and can realize step-by-step release of drugs.

[0017] 4. Through the layer-by-layer encapsulation technology, the matrix and tumor are broken through one by one, and the curative effect of pancreatic cancer is improved. BRIEF DESCRIPTION OF DRAWINGS

[0018] Figure 1 It is a physical map of Si-G@Ca-H of the present application; Figure 2 It is a TEM map of Si-G@Ca-H of the present application; Figure 3 It is a DLS distribution map of MSNs, Si-G, Si-G@Ca, Si-G@Ca-H of the present application; Figure 4 It is a UV-Vis schematic diagram of MSNs, Si-G, Si-G@Ca, Si-G@Ca-H of the present application; Figure 5 It is a SEM comparison diagram of Si-G@Ca before and after incubation in a slightly acidic environment of the present application; Figure 6 It is a TEM map of MSNs of the present application; Figure 7 It is a SEM map of MSNs of the present application. DETAILED DESCRIPTION

[0019] Please refer to Figures 1-7The application provides a technical scheme: a multi-stage rocket structure nanometer material, taking mesoporous silica (MSNs) as a core, loading gemcitabine (GEM) in the core, forming an intermediate layer by coating the core with calcium carbonate, loading halofentine (HF) on the intermediate layer, and connecting a targeting molecule to the outermost layer to form a core-shell structure; the mesoporous silica (MSNs) has a particle size of about 120 nm, a specific surface area of 307.78 m 2 / g, and a pore size of 13.01 nm; the nanometer material has pH and GSH dual responsiveness, and the outermost layer of calcium carbonate collapses in a slightly acidic environment with a pH of 6.2-6.5, and the innermost layer of mesoporous silica (MSNs) further collapses in a 10 mM GSH environment.

[0020] As a further scheme of the application, the raw materials for preparing the nanometer material include triethylamine (TEA), cetyltrimethylammonium bromide (CTAB), sodium salicylate (Nasal), tetraethyl orthosilicate (TEOS), 1,2-bis(triethoxysilyl)ethane (BTES), ethanol, hydrochloric acid, methanol, calcium chloride, gemcitabine (GEM), halofentine (HF), and a targeting molecule.

[0021] A preparation method of a multi-stage rocket structure nanometer material with mesoporous silica as an inner core, comprising the following steps: Step one: synthesizing mesoporous silica (MSNs) by a solvent template method; Synthesis of mesoporous silica (MSNs): 122 µL of triethylamine (TEA) is dispersed in 50 mL of water and stirred at 80℃ for 0.5 h. Then 720 mg of cetyltrimethylammonium bromide (CTAB) and 300 mg of sodium salicylate (Nasal) are added to the above solution and continuously stirred at 80℃ for 2 h. After mixing 4 mL of tetraethyl orthosilicate (TEOS) and 3.5 mL of 1,2-bis(triethoxysilyl)ethane (BTES), they are added dropwise into the above solution and continuously stirred at 80℃ for 12 h. The product is collected by centrifugation and washed with ethanol for 3 times. Then the product is dispersed in a 2M HCl / methanol solution, stirred at 75℃ for 24 h to remove the template to obtain mesoporous silica (MSNs).

[0022] Step two: loading gemcitabine (GEM) by overnight stirring to make it adsorbed in the mesopores of mesoporous silica (MSNs) to obtain Si-G; Synthesis of Si-G: 20 mg of mesoporous silica (MSNs) and 10 mg of gemcitabine (GEM) are added to 10 mL of deionized water, stirred for 12 h, centrifuged and washed, and then freeze-dried to obtain Si-G.

[0023] Step 3: Obtain Si-G@Ca through gas diffusion and acid etching; Synthesis of Si-G@Ca: 150 mg CaCl2 and 50 mg Si-G were added to a 250 mL beaker, followed by 100 mL of anhydrous ethanol. The beaker was then covered with perforated aluminum foil. 5 g NH4HCO3 was placed in a 50 mL centrifuge tube and covered with perforated aluminum foil. Both liquids were placed in a sealed 40°C vacuum oven. After incubation for 24 hours, the sample was collected by centrifugation at 9000 rpm for 10 min, washed with deionized water, and dried. The product was then incubated in PBS at pH 6.5 for 2.5 h, centrifuged at 9000 rpm for 10 min, and the sample was collected, washed with deionized water, and dried to obtain Si-G@Ca.

[0024] Step 4: Loading acetophenone (HF) to obtain Si-G@Ca-H; Synthesis of Si-G@Ca-H: Si-G@Ca and fentanyl (HF) were dissolved in ethanol solution in equal mass ratio. After reacting overnight, the sample was collected by centrifugation at 9000 rpm for 10 min, washed with deionized water and dried to obtain Si-G@Ca-H.

[0025] Step 5: Connect the target molecules to obtain the final formulation, namely a multi-stage rocket structure nanomaterial with mesoporous silica as the core.

[0026] As a further aspect of the present invention, the solvent template method described in step one uses triethylamine as a weak base and surfactant. Through its tertiary amine group, it forms a hydrogen bond network with water, providing an alkaline microenvironment for the subsequent formation of hexadecyltrimethylammonium bromide (CTAB) micelles. Heating at 80°C can accelerate molecular motion and promote system homogenization.

[0027] As a further aspect of the present invention, in step one, cetyltrimethylammonium bromide (CTAB) and sodium salicylate (Nasal) are co-dissolved. Cetyltrimethylammonium bromide (CTAB) acts as a cationic surfactant, forming rod-shaped micelles under alkaline conditions, which constitute the framework of the mesoporous template. Sodium salicylate (Nasal) acts as a co-templating agent, which regulates the micelles and stabilizes the mesoporous walls through electrostatic interaction with the cation of cetyltrimethylammonium bromide (CTAB). The micelles are continuously stirred at 80°C for 2 hours to ensure that they fully self-assemble.

[0028] As a further aspect of the present invention, in step one, tetraethyl orthosilicate (TEOS) and ethane (BTES) are added, and the two undergo a hydrolysis-condensation reaction under alkaline conditions. The reaction is continued at 80°C for 12 hours to ensure complete silanization, thereby obtaining mesoporous silica (MSNs).

[0029] As a further scheme of the present application, the preliminarily obtained mesoporous silica (MSNs) needs to be dispersed in a 2M HCl / methanol solution, stirred at 75°C for 24 h to remove cetyltrimethylammonium bromide (CTAB), and finally obtain mesoporous silica (MSNs).

[0030] Application of a multi-stage rocket structure nanomaterial with mesoporous silica as the core: through layer-by-layer encapsulation technology, it is applied to step-by-step release of drugs in the tumor microenvironment, breakthrough of the dense stroma barrier of pancreatic cancer, improvement of drug delivery efficiency, and great potential in the treatment of pancreatic cancer.

[0031] Example 2: Step one: synthesis of mesoporous silica (MSNs): 122 μL of triethylamine (TEA) was dispersed in 50 mL of water and stirred at 80°C for 0.5 h. Then cetyltrimethylammonium bromide (CTAB), sodium salicylate (Nasal) were added to the above solution according to a mass ratio of 2.4:1, and stirring was continued at 80°C for 2 h. 4 mL of tetraethyl orthosilicate (TEOS) and 3.5 mL of 1,2-bis(triethoxysilyl)ethane (BTES) were mixed and added dropwise into the above solution, and stirring was continued at 80°C for 12 h. The product was collected by centrifugation and washed with ethanol for 3 times. Then the product was dispersed in a 2M HCl / methanol solution, stirred at 75°C for 24 h to remove the template to obtain mesoporous silica (MSNs).

[0032] Step two: synthesis of Si-G: 20 mg of mesoporous silica (MSNs) and 10 mg of gemcitabine (GEM) were added to 10 mL of deionized water, stirred for 12 h, and then freeze-dried after centrifugal washing to obtain Si-G.

[0033] Step three: synthesis of Si-G@Ca: 150 mg of CaCl2 and 50 mg of Si-G were added to a 250 mL beaker, 100 mL of anhydrous ethanol was added, and the beaker was covered with a tin foil with holes. Then 5 g of NH4HCO3 was placed in a 50 mL centrifuge tube, which was covered with a tin foil with holes. The two bottles of liquid were placed in a sealed 40°C vacuum oven. After incubation for 24 hours, the sample was collected by centrifugation at 9000 rpm for 10 min, washed with deionized water, and dried. The product was incubated in PBS at pH=6.5 for 2.5 h, the sample was collected by centrifugation at 9000 rpm for 10 min, and then dried after washing with deionized water to obtain Si-G@Ca.

[0034] Step four: Synthesis of Si-G@Ca-H: Si-G@Ca-H was synthesized by dissolving Si-G@Ca and halofenate (HF) in ethanol solution with equal mass ratio. After reaction overnight, the sample was collected by centrifugation at 9000 rpm for 10 min, washed with deionized water, and dried to obtain Si-G@Ca-H.

[0035] Example 3: Step one: Synthesis of mesoporous silica (MSN): 122 μL of triethylamine (TEA) was dispersed in 50 mL of water and stirred at 80 °C for 0.5 h. Then cetyltrimethylammonium bromide (CTAB) and sodium salicylate (Nasal) were added to the above solution with a mass ratio of 2.4:1 and stirred continuously at 80 °C for 2 h. 4 mL of tetraethyl orthosilicate (TEOS) and 3.5 mL of 1,2-bis(triethoxysilyl)ethane (BTES) were mixed and added dropwise into the above solution, and stirred continuously at 80 °C for 12 h. The product was collected by centrifugation and washed with ethanol for 3 times. Then the product was dispersed in 2M HC1 / methanol solution, stirred at 75 °C for 24 h to remove the template to obtain mesoporous silica (MSN).

[0036] Step two: Synthesis of Si-G: Si-G was synthesized by adding mesoporous silica (MSN) and gemcitabine (GEM) to 10 mL of ethanol with a mass ratio of 1:1, stirring for 12 h, and freeze-drying after centrifugal washing to obtain Si-G.

[0037] Step three: Synthesis of Si-G@Ca: 150 mg of CaCl2 and 50 mg of Si-G were added to a 250 mL beaker, 100 mL of anhydrous ethanol was added, and the beaker was covered with a tin foil with holes. Then 5 g of NH4HCO3 was placed in a 50 mL centrifuge tube, which was covered with a tin foil with holes. The two bottles of liquid were placed in a sealed 40 °C vacuum oven. After incubation for 24 hours, the sample was collected by centrifugation at 9000 rpm for 10 min, washed with deionized water, and dried. The product was incubated in PBS with pH=6.5 for 2.5 h, the sample was collected by centrifugation at 9000 rpm for 10 min, washed with deionized water, and dried to obtain Si-G@Ca.

[0038] Step four: Synthesis of Si-G@Ca-H: Si-G@Ca-H was synthesized by dissolving Si-G@Ca and halofenate (HF) in ethanol solution with equal mass ratio. After reaction overnight, the sample was collected by centrifugation at 9000 rpm for 10 min, washed with deionized water, and dried to obtain Si-G@Ca-H.

[0039] Example 4: Step one: Synthesis of mesoporous silica (MSN): 122 µL of triethylamine (TEA) was dispersed in 50 mL of water and stirred at 80 °C for 0.5 h. Then cetyltrimethylammonium bromide (CTAB), sodium salicylate (Nasal) were added into the above solution with a mass ratio of 2.4:1 and stirred at 80 °C for 2 h. 4 mL of tetraethyl orthosilicate (TEOS) and 3.5 mL of 1,2-bis(triethoxysilyl)ethane (BTES) were mixed and added into the above solution dropwise and stirred at 80 °C for 12 h. The product was collected by centrifugation and washed with ethanol for 3 times. Then the product was dispersed in 2M HCl / methanol solution and stirred at 75 °C for 24 h to remove the template to obtain mesoporous silica (MSN).

[0040] Step two: Synthesis of Si-G: Mesoporous silica (MSN) and gemcitabine (GEM) were added into 10 mL of ethanol with a mass ratio of 1:1, stirred for 12 h, centrifuged and washed, and then freeze-dried to obtain Si-G.

[0041] Step three: Synthesis of Si-G@Ca: 150 mg of CaCl2 and 50 mg of Si-G were added to a 250 mL beaker, 100 mL of anhydrous ethanol was added, and the beaker was covered with a tin foil with holes. Then 5 g of NH4HCO3 was placed in a 50 mL centrifuge tube, which was covered with a tin foil with holes. The two bottles of liquid were placed in a sealed 40 °C vacuum oven. After incubation for 24 hours, the sample was collected by centrifugation at 9000 rpm for 10 min, washed with deionized water, and dried. The product was incubated in PBS at pH = 6.2 for 2 h, the sample was collected by centrifugation at 9000 rpm for 10 min, washed with deionized water, and dried to obtain Si-G@Ca.

[0042] Step four: Synthesis of Si-G@Ca-H: Si-G@Ca and halofuginone (HF) were dissolved in ethanol solution with an equal mass ratio, the sample was collected by centrifugation at 9000 rpm for 10 min after overnight reaction, washed with deionized water, and dried to obtain Si-G@Ca-H.

[0043] Example 5: Step one: Synthesis of mesoporous silica (MSN): 122 μL of triethylamine (TEA) was dispersed in 50 mL of water and stirred at 80 °C for 0.5 h. Then cetyltrimethylammonium bromide (CTAB), sodium salicylate (Nasal) were added into the above solution with a mass ratio of 2.4:1 and stirred at 80 °C for 2 h. 4 mL of tetraethyl orthosilicate (TEOS) and 3.5 mL of 1,2-bis(triethoxysilyl)ethane (BTES) were mixed and added into the above solution dropwise and stirred at 80 °C for 12 h. The product was collected by centrifugation and washed with ethanol for 3 times. Then the product was dispersed in 2M HC1 / methanol solution and stirred at 75 °C for 24 h to remove the template to obtain mesoporous silica (MSN).

[0044] Step two: Synthesis of Si-G: Mesoporous silica (MSN) and gemcitabine (GEM) were added into 10 mL of ethanol with a mass ratio of 1:1, stirred for 12 h, centrifuged and washed, and then freeze-dried to obtain Si-G.

[0045] Step three: Synthesis of Si-G@Ca: 150 mg of CaCl2 and 50 mg of Si-G were added to a 250 mL beaker, 100 mL of anhydrous ethanol was added, and the beaker was covered with a tin foil with holes. Then 5 g of NH4HCO3 was placed in a 50 mL centrifuge tube, which was covered with a tin foil with holes. The two bottles of liquid were placed in a sealed 40 °C vacuum oven. After incubation for 24 hours, the sample was collected by centrifugation at 9000 rpm for 10 min, washed with deionized water, and dried. The product was incubated in PBS at pH = 6.2 for 2 h, the sample was collected by centrifugation at 9000 rpm for 10 min, washed with deionized water, and dried to obtain Si-G@Ca.

[0046] Step four: Synthesis of Si-G@Ca-H: Si-G@Ca and halofuginone (HF) were dissolved in methanol solution with an equal mass ratio, the sample was collected by centrifugation at 9000 rpm for 10 min after overnight reaction, washed with deionized water, and dried to obtain Si-G@Ca-H.

Claims

1. A nanomaterial for a multi-stage rocket structure, characterized in that: The nanomaterial has a core of mesoporous silica, with gemcitabine encapsulated within the core. The outer layer of the core is coated with calcium carbonate to form an intermediate layer, which is loaded with styraxone. The outermost layer is connected to a target molecule, forming a core-shell structure. The nanomaterial has dual pH and GSH responsiveness. In a slightly acidic environment of pH=6.2-6.5, the outer layer of calcium carbonate disintegrates. In a 10mM GSH environment, the inner layer of mesoporous silica further disintegrates, which is a multi-stage rocket structure nanomaterial with mesoporous silica as the core.

2. The multi-stage rocket structure nanomaterial with mesoporous silicon as its core according to claim 1, characterized in that: The raw materials for preparing the nanomaterials include triethylamine, hexadecyltrimethylammonium bromide, sodium salicylate, tetraethyl orthosilicate, 1,2-bis(triethoxysilyl)ethane, ethanol, hydrochloric acid, methanol, calcium chloride, gemcitabine, styraxone, and targeting molecules.

3. A method for preparing a multi-stage rocket structure nanomaterial, applicable to the multi-stage rocket structure nanomaterial with mesoporous silicon as its core as described in any one of claims 1-2, characterized in that: Includes the following steps: Step 1: Synthesize mesoporous silica using the solvent template method; Step 2: After overnight stirring, gemcitabine is loaded and adsorbed into the mesoporous silica pores to obtain Si-G; Step 3: Obtain Si-G@Ca through gas diffusion and acid etching; Step 4: Loading halogenated ketone to obtain Si-G@Ca-H; Step 5: Connect the target molecules to obtain the final formulation, namely a multi-stage rocket structure nanomaterial with mesoporous silica as the core.

4. The method for preparing a multi-stage rocket structure nanomaterial according to claim 3, characterized in that: The solvent template method described in step one uses triethylamine as a weak base and surfactant. Through its tertiary amine group, it forms a hydrogen bond network with water, providing an alkaline microenvironment for the subsequent formation of hexadecyltrimethylammonium bromide micelles. Heating at 80°C can accelerate molecular motion and promote system homogenization.

5. The method for preparing a multi-stage rocket structure nanomaterial according to claim 4, characterized in that: In step one, cetyltrimethylammonium bromide and sodium salicylate need to be co-dissolved. Cetyltrimethylammonium bromide, as a cationic surfactant, forms rod-shaped micelles under alkaline conditions, which constitute the framework of the mesoporous template. Sodium salicylate, as a co-templating agent, regulates the micelles and stabilizes the mesoporous walls through electrostatic interaction with the cetyltrimethylammonium bromide cation. Stirring continuously at 80°C for 2 hours ensures that the micelles fully self-assemble.

6. The method for preparing a multi-stage rocket structure nanomaterial according to claim 3, characterized in that: In step one, tetraethyl orthosilicate and ethane are added. The two undergo a hydrolysis-condensation reaction under alkaline conditions and are continuously reacted at 80°C for 12 hours to ensure complete silanization, resulting in mesoporous silica.

7. The method for preparing a multi-stage rocket structure nanomaterial according to claim 3, characterized in that: In step one, the initially obtained mesoporous silica needs to be dispersed in a 2M HCl / methanol solution and refluxed and stirred at 75°C for 24 h to remove hexadecyltrimethylammonium bromide, and finally mesoporous silica is obtained.

8. An application of a nanomaterial for a multi-stage rocket structure according to any one of claims 1-2, characterized in that: The nanomaterials, through layer-by-layer encapsulation technology, are applied to enable the stepwise release of drugs in the tumor microenvironment, breaking through the dense matrix barrier of pancreatic cancer and improving drug delivery efficiency.

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