CN113230412B - Mesoporous silica-lipid composite nano material and preparation method and application thereof - Google Patents
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Abstract
The invention discloses a mesoporous silica-lipid composite nano material and a preparation method and application thereof, wherein the mesoporous silica-lipid composite nano material is composed of amino mesoporous silica and lipid, and the mass ratio of the amino mesoporous silica to the lipid is (5-20) to (20-44). The invention provides a mesoporous silica-lipid composite nano material which is in a core-shell nano particle structure, wherein the particle size of dry particles under an electron microscope is about 20nm, and the hydrated particle size is about 32nm under a neutral condition; the hydrated particle size was reduced to about 17nm under acidic pH triggering. When the mesoporous silica-lipid composite nano material is intravenously injected into a tumor-bearing mouse body, the mesoporous silica-lipid composite nano material can be effectively accumulated to a tumor tissue, and then the particle size is reduced in an acidic environment of the tumor tissue, so that the deep penetration of the tumor tissue is realized. After the anti-cancer drug is loaded, the nano material can effectively kill tumor cells and obviously inhibit the growth of tumors.
Description
Technical Field
The invention belongs to the technical field of nano material preparation, and particularly relates to a mesoporous silica-lipid composite nano material as well as a preparation method and application thereof.
Background
The nano material is used for loading the chemotherapeutic drug, which is beneficial to reducing the whole body toxicity of the drug, improving the in vivo circulation of the drug and improving the therapeutic effect of the drug, and plays an important role in tumor therapy. The distribution of the nano material in the tumor tissue directly influences the treatment effect of the drug loaded on the nano material. The research of the Canadian cancer research center shows that the volatilization of the drug effect of the anti-tumor drug depends on the effective accumulation and deep penetration of the drug-loaded nano material in tumor tissues (nat. Rev. cancer2006,6: 583-592). In addition, multiple scientific researches at home and abroad show that the difficulty of the drug-loaded nano material to penetrate into the deep part of the tumor tissue is the main reason of tumor metastasis and recurrence (nat. Rev. cancer2006,6: 583. about. 592; nat. Rev. Mater.2017,2: 17024. about. 17042; adv. drug Deliver. Rev.2017,109: 119. about. 130). However, to achieve effective tumor accumulation and deep penetration, drug-loaded nanomaterials delivered from the intravenous site to the tumor cells must overcome a series of biological barriers. At present, effective nano-drug carriers designed for tumor therapy face the dilemma between effective tumor accumulation and deep tumor penetration. Studies have shown that the larger size of the nanocarriers favors the accumulation to tumor tissues through the EPR effect, but their diffusion resistance in the tumor stroma is large and it is difficult to penetrate to the deep tumor sites (nat. nanotechnol.2007,2: 751-. In contrast, the smaller size nanocarriers have greater tumor penetration and more uniform diffusion distribution in tumor tissues, but have lower tumor accumulation (nat. Rev. Clin. Oncol.2010,7: 653-664; nat. Nanotechnol.2009,5: 42-47; Small 2013,9: 1450-1466). Therefore, designing a nano-drug carrier with high tumor accumulation and deep tumor permeability is a very challenging task.
The mesoporous silica nanoparticles are very common nano drug carriers, and have the excellent characteristics of good biocompatibility, adjustable particle size, easy surface modification, large specific surface area, narrow pore size distribution and the like, so that the mesoporous silica nanoparticles are widely concerned and researched by researchers at home and abroad. In order to improve the accumulation and penetration of mesoporous silica nanoparticles in tumor tissues, some researchers at home and abroad aim to improve the surface properties of the mesoporous silica nanoparticles with larger sizes. For example, Weibo Cai team (ACSNano 2013,7:9027-9039) of the university of Wisconsin and Campylone courier team (adv. Mater.2014,26:6742-6748) of the department of science modify a targeting ligand on the surface of the large-size mesoporous silica nanoparticles, thereby effectively improving the tumor accumulation amount and promoting the deep penetration of the tumor. However, the ligand is easily captured and digested by endosomes, and the effectiveness is poor, so that the application of the method is limited. Some researchers have promoted the deep penetration of large-sized mesoporous silica nanoparticles in tumor tissues by digesting the tumor stroma (Nano Lett.2019,19: 997-1008; ACS Nano 2014,8: 9874-9883; chem. Mater.2018,30: 112-120). However, digesting the tumor stroma increases the risk of tumor growth and metastasis. In addition, some investigators have reduced interstitial fluid pressure in tumor stroma by restoring and normalizing tumor blood vessels to promote deep penetration of particles into tumor tissue (adv. drug delivery. rev.2018,136-137: 49-61). However, tumor vascular repair may damage the normal vascular system, increasing the risk of thrombosis and tumor metastasis. In addition, large-sized mesoporous silica nanoparticles are difficult to remove from the body due to their size limitation and poor biodegradability, and are likely to cause biotoxicity.
The mesoporous silica nano material as a drug carrier has some serious problems in the aspect of tumor treatment, which limits further application of the mesoporous silica nano material. Based on the structure, the development of a novel mesoporous silica-based nano drug carrier which integrates high-efficiency tumor accumulation, deep tumor permeability and renal clearance simultaneously has very important significance.
Disclosure of Invention
The invention aims to provide a mesoporous silica-lipid composite nano material capable of realizing effective tumor accumulation, deep tumor penetration and rapid in vivo removal, and a preparation method and application thereof.
The mesoporous silica-lipid composite nanomaterial consists of amino mesoporous silica and lipid, wherein the mass ratio of the amino mesoporous silica to the lipid is (5-20) to (20-44).
The lipid comprises soybean phospholipid, cholesterol and 9-carbon-chain spiropyran, wherein the mass ratio of the soybean phospholipid to the cholesterol to the 9-carbon-chain spiropyran is (15-40) to (3-8) to (0.5-1). The average particle size of the mesoporous silica-lipid composite nano material is 10-20 nm.
The preparation method of the mesoporous silica-lipid composite nano material comprises the following steps:
1) preparing an amino silicon dioxide nano material: dissolving CTAB in a mixed solution composed of deionized water and ammonia water, stirring until CTAB is dissolved, adding methyl orthosilicate and 3-aminopropyltriethoxysilane, and continuing stirring for reaction; after the reaction is finished, freeze drying to obtain the amino silicon dioxide nano material;
2) preparation of amino mesoporous silica nanomaterial: dispersing the amino silicon dioxide nano material in a mixed solvent consisting of ethanol and hydrochloric acid, stirring and reacting to remove CTAB, and obtaining the amino mesoporous silicon dioxide nano material;
3) preparation of lipid membrane: dissolving soybean phospholipid, cholesterol and 9-carbon chain spiropyran in ethanol, and removing the ethanol in vacuum to obtain a lipid membrane;
4) preparing a composite nano material: the amino mesoporous silica nano material suspension is used for hydrating lipid membranes to obtain the mesoporous silica-lipid composite nano material.
In the step 1), the volume ratio of the deionized water to the ammonia water is (200-400) to (0.031-1.254); the mass volume ratio of CTAB to the mixed solution is (1.67-3.35) to (200-402) g/mL; the mass ratio of CTAB, methyl orthosilicate and 3-aminopropyltriethoxysilane is (1.67-3.35): (1.31-2.61): (1.41-2.51); the stirring reaction temperature is 25-80 ℃, and the stirring reaction time is 2-30 h.
In the step 2), the volume ratio of the ethanol to the hydrochloric acid is (80-95) to (5-20); the mass volume ratio of the amino silicon dioxide nano material to the mixed solvent is (400-600): (100-140) mg/mL; the stirring reaction temperature is 60-80 ℃, and the stirring reaction time is 12-36 h.
In the step 3), the mass ratio of the soybean phospholipid to the cholesterol to the 9-carbon chain spiropyran is (15-40) to (3-8) to (0.5-1), and the mass volume ratio of the soybean phospholipid to the ethanol is (15-40): (2-10) mg/mL.
In the step 4), the concentration of the amino mesoporous silica nano material suspension is 1-4 mg/mL, and the mass ratio of the amino mesoporous silica nano material to the lipid membrane is (5-20): 20-44; the hydration temperature is 30-40 ℃, and the hydration time is 15 min-1 h.
The mesoporous silica-lipid composite nano material is applied to a nano drug carrier.
The principle of the invention is as follows: the invention provides a mesoporous silica-lipid composite nano material, which is characterized in that methyl orthosilicate and 3-aminopropyltriethoxysilane are added in the process of forming a micelle-like structure by CTAB self-assembly, and the methyl orthosilicate and the 3-aminopropyltriethoxysilane are hydrolyzed, polycondensed and deposited on the surface of the CTAB micelle to obtain the CTAB micelle structure with an amino silica layer coated on the surface. And then dispersing the CTAB micelle structure with the surface coated with the amino silica layer in a mixed solvent of ethanol and hydrochloric acid, and extracting and removing CTAB in an ion exchange manner to obtain the amino mesoporous silica nano material. Further, the amino mesoporous silica nanomaterial suspension is used to hydrate a lipid membrane prepared from soybean phospholipid, cholesterol and 9-carbon chain spiropyran to obtain the mesoporous silica-lipid composite nanomaterial.
Compared with the prior art, the invention has the beneficial technical effects that:
the invention provides a mesoporous silica-lipid composite nano material which is in a core-shell nano particle structure, wherein the particle size of dry particles under an electron microscope is about 20nm, and the hydrated particle size is about 33nm under a neutral condition; the hydrated particle size was reduced to about 17nm under acidic pH triggering. When the mesoporous silica-lipid composite nano material is injected into a tumor-bearing mouse body intravenously, the mesoporous silica-lipid composite nano material can be effectively accumulated to tumor tissues, and then the particle size is reduced in the acidic environment of the tumor tissues, so that the deep penetration of the tumor tissues is realized. After the anti-cancer drug is loaded, the nano material can effectively kill tumor cells and obviously inhibit the growth of tumors.
The preparation process of the mesoporous silica-lipid composite nanomaterial, provided by the invention, has the advantages of simplicity in operation, good repeatability, short preparation period, low cost and convenience for popularization of large-scale industrial production.
Drawings
Fig. 1 is a TEM picture of the mesoporous silica-lipid composite nanomaterial prepared in example 1.
Fig. 2 is a hydrated particle size of the mesoporous silica-lipid composite nanomaterial prepared in example 1 in a neutral aqueous solution.
Fig. 3 is a graph showing hydrated particle size changes of the mesoporous silica-lipid composite nanomaterial prepared in example 1 in solutions with different pH.
Fig. 4 is a graph showing tumor tissue accumulation of the mesoporous silica-lipid composite nanomaterial prepared in example 1 after intravenous injection into a tumor-bearing mouse.
Fig. 5 is a tumor permeation map of the mesoporous silica-lipid composite nanomaterial prepared in example 1 after intravenous injection into tumor-bearing mice.
Fig. 6 is a graph showing the excretion amount of the mesoporous silica-lipid composite nanomaterial prepared in example 1 after intravenous injection into a rat body, the excretion amount being discharged from the body via urine and feces.
Fig. 7 is a graph of ultraviolet absorption spectra of the mesoporous silica-lipid composite nanomaterial prepared in examples 1 and 5 and anticancer drug doxorubicin loaded thereon.
Fig. 8 is a graph showing the killing effect of the mesoporous silica-lipid composite nanomaterial prepared in example 5 on tumor cell cancer after loading the anticancer drug doxorubicin.
Fig. 9 is a graph showing the effect of the mesoporous silica-lipid composite nanomaterial prepared in example 5 on tumor growth inhibition after anticancer drug doxorubicin is loaded.
Detailed Description
The invention will be further elucidated with reference to the embodiments and the accompanying drawings.
Example 1
The preparation process of the mesoporous silica-lipid composite nanomaterial in the embodiment comprises the following steps:
dissolving 1.67g of CTAB in a mixed solvent of 200mL of deionized water and 31 mu L of ammonia water, stirring for 30min in a 30 ℃ water bath kettle to completely dissolve the CTAB, adding 1.28mL of methyl orthosilicate and 1.5mL of 3-aminopropyltriethoxysilane, and continuously stirring for 24h in the 30 ℃ water bath kettle; and (5) freeze-drying to obtain the amino silicon dioxide nano material. 500mg of amino silicon dioxide nano material is placed in 120mL of mixed solvent consisting of 90% ethanol and 10% hydrochloric acid, stirred, refluxed and stirred for 24h at 70 ℃, centrifuged to remove supernatant solution, washed with ethanol and deionized water for several times, and vacuum-dried to obtain the amino mesoporous silicon dioxide nano material. Dispersing 10mg of amino mesoporous silica nano material in 5mL of deionized water, then transferring the nano material into a lipid membrane prepared in advance by 17.7mg of soybean lecithin, 3.54mg of cholesterol and 0.5mg of 9-carbon-chain spiropyran (the preparation of the lipid membrane is obtained by adding the three components into 2mL of ethanol according to the mass and then vacuumizing the ethanol), and hydrating at 37 ℃ for 15min to obtain the mesoporous silica-lipid composite nano material.
The mesoporous silica-lipid composite nanomaterial in the present embodiment is composed of amino mesoporous silica and lipid, and the mass ratio of the amino mesoporous silica to the lipid is 10: 21.74.
The volume ratio of deionized water to ammonia water in this example was 200: 0.031.
The mass of CTAB, methyl orthosilicate, and 3-aminopropyltriethoxysilane in this example was 1.67:1.31: 1.41.
The stirring reaction temperature of the amino silicon dioxide nano material in the embodiment is 30 ℃, and the stirring time is 24 h.
The temperature of the hydration reaction of the mesoporous silica-lipid composite nanomaterial in this embodiment is 37 ℃, and the hydration time is 15 min.
Example 2
The preparation process of the mesoporous silica-lipid composite nanomaterial in the embodiment comprises the following steps:
dissolving 2g of CTAB in a mixed solvent of 200mL of deionized water and 63 mu L of ammonia water, placing the mixed solvent in a 40 ℃ water bath kettle, stirring for 30min to completely dissolve the CTAB, adding 1.5mL of methyl orthosilicate and 2mL of 3-aminopropyltriethoxysilane, and continuously stirring in the 40 ℃ water bath kettle for 16 h; and (5) freeze-drying to obtain the amino silicon dioxide nano material. 500mg of amino silicon dioxide nano material is placed in 120mL of mixed solvent consisting of 90% ethanol and 10% hydrochloric acid, stirred, refluxed and stirred for 24h at 70 ℃, centrifuged to remove supernatant solution, washed with ethanol and deionized water for several times, and vacuum-dried to obtain the amino mesoporous silicon dioxide nano material. Dispersing 10mg of amino mesoporous silica nano material in 5mL of deionized water, then transferring the nano material into a lipid membrane prepared in advance from 35.4mg of soybean lecithin, 7.08mg of cholesterol and 1mg of 9-carbon-chain spiropyran (the preparation of the lipid membrane is obtained by adding the three components into 10mL of ethanol according to the mass and then removing the ethanol in vacuum), and hydrating the nano material at 37 ℃ for 30min to obtain the mesoporous silica-lipid composite nano material.
The mesoporous silica-lipid composite nanomaterial in the embodiment is composed of amino mesoporous silica and lipid, wherein the mass ratio of the amino mesoporous silica to the lipid is 10: 43.48.
The volume ratio of deionized water to ammonia in this example was 200: 0.063.
The mass of CTAB, methyl orthosilicate and 3-aminopropyltriethoxysilane in this example was 2:1.542: 1.892.
The stirring reaction temperature of the amino silicon dioxide nano material in the embodiment is 40 ℃, and the stirring time is 16 h.
The temperature of the hydration reaction of the mesoporous silica-lipid composite nanomaterial in this embodiment is 37 ℃, and the hydration time is 30 min.
Example 3
The preparation process of the mesoporous silica-lipid composite nanomaterial in the embodiment comprises the following steps:
dissolving 2g of CTAB in a mixed solvent of 240mL of deionized water and 63 mu L of ammonia water, placing the mixed solvent in a water bath kettle at 25 ℃ and stirring for 30min to completely dissolve the CTAB, adding 2mL of methyl orthosilicate and 2.5mL of 3-aminopropyltriethoxysilane, and continuing stirring in the water bath kettle at 30 ℃ for 12 h; and (5) freeze-drying to obtain the amino silicon dioxide nano material. 500mg of amino silicon dioxide nano material is placed in 120mL of mixed solvent consisting of 90% ethanol and 10% hydrochloric acid, stirred, refluxed and stirred for 24h at 70 ℃, centrifuged to remove supernatant solution, washed with ethanol and deionized water for several times, and vacuum-dried to obtain the amino mesoporous silicon dioxide nano material. Dispersing 5mg of amino mesoporous silica nano material in 5mL of deionized water, then transferring the nano material into a lipid membrane prepared in advance by 17.7mg of soybean lecithin, 3.54mg of cholesterol and 0.5mg of 9-carbon-chain spiropyran (the lipid membrane is prepared by adding the three components into 5mL of ethanol according to the mass and then removing the ethanol in vacuum), and hydrating for 1h at 37 ℃ to obtain the mesoporous silica-lipid composite nano material.
The mesoporous silica-lipid composite nanomaterial in the embodiment is composed of amino mesoporous silica and lipid, wherein the mass ratio of the amino mesoporous silica to the lipid is 5: 21.74.
The volume ratio of deionized water to aqueous ammonia in this example was 240: 0.063.
The mass of CTAB, methyl orthosilicate and 3-aminopropyltriethoxysilane in this example was 2:2.046: 2.365.
The stirring reaction temperature of the amino silicon dioxide nano material in the embodiment is 30 ℃, and the stirring time is 12 h.
The temperature of the hydration reaction of the mesoporous silica-lipid composite nanomaterial in this embodiment is 30 ℃, and the hydration time is 1 h.
Example 4
The preparation process of the mesoporous silica-lipid composite nanomaterial in the embodiment comprises the following steps:
dissolving 3.54g of CTAB in a mixed solvent of 400mL of deionized water and 0.6mL of ammonia water, placing the mixed solvent in a water bath kettle at 25 ℃ and stirring for 30min to completely dissolve the CTAB, adding 2.5mL of methyl orthosilicate and 3mL of 3-aminopropyltriethoxysilane, and continuing stirring in the water bath kettle at 25 ℃ for 30 h; and (5) freeze-drying to obtain the amino silicon dioxide nano material. And (2) placing 500mg of amino silicon dioxide nano material in 120mL of mixed solvent consisting of 90% ethanol and 10% hydrochloric acid, stirring, refluxing and stirring for 24h at 70 ℃, centrifuging to remove supernatant solution, washing with ethanol and deionized water for several times, and drying in vacuum to obtain the amino mesoporous silicon dioxide nano material. Dispersing 20mg of amino mesoporous silica nano material into 5mL of deionized water, then transferring the nano material into a lipid membrane prepared in advance by 17.7mg of soybean lecithin, 3.54mg of cholesterol and 0.5mg of 9-carbon-chain spiropyran (the preparation of the lipid membrane is obtained by adding the three components into 5mL of ethanol according to the mass and then vacuumizing the ethanol), and hydrating at 40 ℃ for 40min to obtain the mesoporous silica-lipid composite nano material.
The mesoporous silica-lipid composite nanomaterial in the embodiment is composed of amino mesoporous silica and lipid, wherein the mass ratio of the amino mesoporous silica to the lipid is 20: 21.74.
The volume ratio of deionized water to ammonia in this example was 240: 0.6.
The mass of CTAB, methyl orthosilicate, and 3-aminopropyltriethoxysilane in this example was 3.54:2.55: 2.83.
The stirring reaction temperature of the amino silicon dioxide nano material in the embodiment is 25 ℃, and the stirring time is 30 h.
The temperature of the hydration reaction of the mesoporous silica-lipid composite nanomaterial in this embodiment is 40 ℃, and the hydration time is 40 min.
Example 5
Dispersing 10mg of amino mesoporous silica nano material in 5mL of deionized water containing 1mg of adriamycin, stirring the mixture at 25 ℃ in a dark place for 24 hours, transferring the mixture into a lipid membrane prepared in advance from 17.7mg of soybean phospholipid, 3.54mg of cholesterol and 0.5mg of 9-carbon-chain spiropyran (the lipid membrane is prepared by adding the three components into 2mL of ethanol according to the mass, then removing the ethanol in a vacuum manner), hydrating the mixture for 20 minutes at 37 ℃, and centrifuging the mixture to remove the supernatant, thereby obtaining the adriamycin-loaded mesoporous silica-lipid composite nano material.
The mass ratio of the amino mesoporous silica to the lipid to the doxorubicin in this example was 10:21.74: 1.
The volume ratio of deionized water to ammonia in this example was 240: 0.6.
The stirring reaction temperature of the amino silicon dioxide nano material in the embodiment is 25 ℃, and the stirring time is 24 h.
The temperature of the hydration reaction of the doxorubicin-loaded mesoporous silica-lipid composite nanomaterial in this example was 37 ℃, and the hydration time was 20 min.
Example 6 characterization and analysis
The shape, structural characterization and performance analysis of the mesoporous silica-lipid composite nanomaterial are as follows:
FIG. 1 is a TEM image of the mesoporous silica-lipid composite nanomaterial of example 1, and it can be seen from the TEM image that the composite nanomaterial is spherical in core-shell structure, uniform in particle size and about 20nm in particle size.
Fig. 2 is a hydrated particle size of the mesoporous silica-lipid composite nanomaterial prepared in example 1 in a neutral aqueous solution. The hydrated particle size was about 32 nm.
Fig. 3 is a graph showing variation of hydrated particle size of the mesoporous silica-lipid composite nanomaterial prepared in example 1 in solutions of different pH. As can be seen from fig. 3, the hydrated particle size of the mesoporous silica-lipid composite nanomaterial remains substantially unchanged at pH 7.4 within 24 hours, which is about 34 nm; under the conditions of pH 6.5 and pH 4.5, the hydrated particle size of the mesoporous silica-lipid composite nanomaterial was found to change significantly, and the hydrated particle size decreased from about 32nm to about 17nm after 4 h. The prepared mesoporous silica-lipid composite nano material has pH response size shrinkage performance.
Fig. 4 is a graph showing tumor tissue accumulation of the mesoporous silica-lipid composite nanomaterial prepared in example 1 after intravenous injection into a tumor-bearing mouse. As can be seen from fig. 4, after the mesoporous silica-lipid composite nanomaterial is injected into a tumor-bearing mouse via tail vein, the mesoporous silica-lipid composite nanomaterial can be rapidly accumulated in tumor tissues, and the accumulation amount increases with the time. The mesoporous silica-lipid composite nano material can be effectively accumulated in tumor tissues through an EPR effect.
Fig. 5 is a tumor permeation map of the mesoporous silica-lipid composite nanomaterial prepared in example 1 after intravenous injection into tumor-bearing mice. As can be seen from fig. 5, the mesoporous silica-lipid composite nanomaterial can overflow tumor blood vessels, diffuse to deep tumor sites, and uniformly distribute in tumor tissues. The mesoporous silica-lipid composite nano material has stronger tumor permeability.
Fig. 6 is a graph showing the excretion amount of the mesoporous silica-lipid composite nanomaterial prepared in example 1 after intravenous injection into a rat body, the excretion amount being discharged from the body via urine and feces. As can be seen from FIG. 6, about 49% of the particles were eliminated from the body by feces and urine 72 hours after the intravenous injection. The mesoporous silica-lipid composite nano material has good in-vivo clearance rate, so that the biological toxicity caused by particle retention can be effectively reduced.
Fig. 7 is a graph of an ultraviolet absorption spectrum of the mesoporous silica-lipid composite nanomaterial prepared in examples 1 and 5 and anticancer drug doxorubicin loaded thereon. As can be seen from fig. 7, the mesoporous silica-lipid composite nanomaterial can support a drug, indicating that it can be an effective drug carrier.
Fig. 8 is a graph showing the killing effect of the mesoporous silica-lipid composite nanomaterial prepared in example 5 on tumor cell cancer after loading the anticancer drug doxorubicin. As can be seen from fig. 8, the mesoporous silica-lipid composite nanomaterial loaded with anticancer drug doxorubicin can deliver the drug into tumor cells to exert a killing effect.
Fig. 9 is a graph showing the effect of the mesoporous silica-lipid composite nanomaterial prepared in example 5 on tumor growth inhibition after loading the anticancer drug doxorubicin. As can be seen from fig. 9, the mesoporous silica-lipid composite nanomaterial can deliver an anticancer drug to tumor tissues, and effectively inhibit tumor growth.
The above-mentioned embodiments only express the centralized implementation mode of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that various changes and modifications can be made by those skilled in the art without departing from the spirit of the invention, and these changes and modifications are all within the scope of the invention. Therefore, the protection scope of the present patent should be subject to the appended claims.
Claims (7)
1. A mesoporous silica-lipid composite nano material is characterized by comprising amino mesoporous silica and lipid, wherein the mass ratio of the amino mesoporous silica to the lipid is (5-20) to (20-44);
the lipid consists of soybean lecithin, cholesterol and 9-carbon-chain spiropyran, wherein the mass ratio of the soybean lecithin to the cholesterol to the 9-carbon-chain spiropyran is (15-40) to (3-8) to (0.5-1);
the average particle size of the mesoporous silica-lipid composite nano material is 10-20 nm.
2. A method for preparing the mesoporous silica-lipid composite nanomaterial according to claim 1, comprising the steps of:
1) preparing an amino silicon dioxide nano material: dissolving CTAB in a mixed solution composed of deionized water and ammonia water, stirring until CTAB is dissolved, adding methyl orthosilicate and 3-aminopropyltriethoxysilane, and continuing stirring for reaction; after the reaction is finished, freeze drying to obtain the amino silicon dioxide nano material;
2) preparation of amino mesoporous silica nanomaterial: dispersing the amino silicon dioxide nano material in a mixed solvent consisting of ethanol and hydrochloric acid, and stirring for reaction to remove CTAB, thereby obtaining the amino mesoporous silicon dioxide nano material;
3) preparation of lipid membrane: dissolving soybean phospholipid, cholesterol and 9-carbon chain spiropyran in ethanol, and removing the ethanol in vacuum to obtain a lipid membrane;
4) preparing a composite nano material: the amino mesoporous silica nano material suspension is used for hydrating lipid membranes to obtain the mesoporous silica-lipid composite nano material.
3. The method for preparing the mesoporous silica-lipid composite nanomaterial according to claim 2, wherein in the step 1), the volume ratio of deionized water to ammonia water is (200-400) to (0.031-1.254); the mass volume ratio of CTAB to the mixed solution is (1.67-3.35) to (200-402) g/mL; the mass ratio of CTAB, methyl orthosilicate and 3-aminopropyltriethoxysilane is (1.67-3.35): (1.31-2.61): (1.41-2.51); the stirring reaction temperature is 25-80 ℃, and the stirring reaction time is 2-30 h.
4. The preparation method of the mesoporous silica-lipid composite nanomaterial according to claim 2, wherein in the step 2), the volume ratio of ethanol to hydrochloric acid is (80-95) to (5-20), and the mass volume ratio of the amino silica nanomaterial to the mixed solvent is (400-600) to (100-140) mg/mL; the stirring reaction temperature is 60-80 ℃, and the stirring reaction time is 12-36 h.
5. The method for preparing the mesoporous silica-lipid composite nanomaterial according to claim 2, wherein in the step 3), the mass ratio of the soybean phospholipids to the cholesterol to the 9-carbon chain spiropyrans is (15-40) to (3-8) to (0.5-1), and the mass-to-volume ratio of the soybean phospholipids to the ethanol is (15-40): (2-10) mg/mL.
6. The method for preparing the mesoporous silica-lipid composite nanomaterial according to claim 2, wherein in the step 4), the concentration of the amino mesoporous silica nanomaterial suspension is 1-4 mg/mL, and the mass ratio of the amino mesoporous silica nanomaterial to the lipid membrane is (5-20): 20-44; the hydration temperature is 30-40 ℃, and the hydration time is 15 min-1 h.
7. The use of the mesoporous silica-lipid composite nanomaterial of claim 1 in the preparation of a nano-drug carrier.
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| US6756217B1 (en) * | 1998-05-29 | 2004-06-29 | Southern Illinois University | Glass composite materials containing alkoxosilane derivative having alterable charge, hydrophobic and hydrophilic groups |
| WO2016158327A1 (en) * | 2015-03-30 | 2016-10-06 | 国立大学法人 東京大学 | Compound for fixing lipid membrane-containing composition, base material modified by compound, method for patterning lipid membrane-containing composition on base material, and method for isolating lipid membrane-containing composition on base material |
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| WO2016158327A1 (en) * | 2015-03-30 | 2016-10-06 | 国立大学法人 東京大学 | Compound for fixing lipid membrane-containing composition, base material modified by compound, method for patterning lipid membrane-containing composition on base material, and method for isolating lipid membrane-containing composition on base material |
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