KR20110000297A - Hollow mesoporous silica capsule and method for preparing the same - Google Patents

Abstract

PURPOSE: A hollow mesoporous silica capsule and a producing method thereof are provided to easily carry enzymes, protein, drugs, and other biomasses and to maintain a relatively large space inside a hollow hole. CONSTITUTION: A hollow mesoporous silica capsule comprises a mesoporous silica side wall and more than one macro pores formed on the silica side wall. The average diameter of the capsule is 20nanometers~1micrometers. The average diameter of a macro pore is 1~500nanometers. A cancer cell specific binding peptide sequence or a vitamin compound is attached to the outside of the silica side wall using an organic functional group. The vitamins compound is folic acid.

Description

Hollow mesoporous silica capsule and method for preparing the same

The present invention relates to a hollow mesoporous silica capsule and a method for manufacturing the same, and more particularly, macroporous and high surface area characteristics, and easily carries enzymes, proteins, various drugs, and other biomaterials having a relatively large size in the hollow. It can be used as a carrier for enzymes and catalysts, or as a drug delivery system, and it is easy to introduce various proteins and vitamin compounds into mesoporous walls. Significantly improved the utilization. In addition, according to the method for manufacturing a hollow mesoporous silica capsule according to the present invention, it is possible to support various sizes of biomaterials that can penetrate into cells without a separate pretreatment process, which is required for synthesizing nanoparticles in a conventional capsule form. It is possible to mass-produce by reducing the synthesis time by simplifying the difficult conditions.

Mesoporous materials have been used as catalysts, adsorbents or carrier materials for a long time because of their high specific surface area over zeolites and the pore size of mesospheres. Recently, mesoporous materials have been applied in various fields to increase their importance and interest. It is a substance becoming. Specifically, mesoporous materials are used in biosensor fields such as drug delivery systems and biochemical reaction detection, in areas where the highest specific surface area of mesoporosity is required, such as selective separation and adsorption reactions of specific substances, fuel cells and energy related projects. The need is even more highlighted.

Among mesoporous materials, the capsule particles having a macroporous spherical or hollow structure having an empty center have special properties such as forming a particularly large surface area in the central portion and having a low density. In particular, such hollow mesoporous capsules have a high specific surface area in the form of capsules and have macroporosity in size, and thus have excellent adsorptive power. It has practical advantages such as protection. In addition, when various particles such as metals, metal oxides, quantum dots, and magnetic bodies are supported on the shell forming the capsule, it may be applied to a wider range of fields than conventional simple mesoporous materials. Therefore, encapsulated mesoporous materials are attracting more and more attention than conventional materials because of these advantages.

Conventionally, in synthesizing hollow mesoporous capsules, supercritical methods using an ultrasonic cavitation method for promoting crystal nucleation, chemical gelation or emulsion templating in a supercritical fluid, etc. Supercritical fluid methods and methods of using flexible or rigid molds have been developed. In general, the mold usage method is carried out by laminating various materials such as inorganic materials, polymers, metals, etc. in a layer-by-layer form around the material of the mold, and the thickness of the shell forming the capsule is determined in the process of synthesis. It is controlled by the concentration of the material to be coated or the time of the synthesis cycle to form the layer. However, there are disadvantages in that it takes a long time for the lamination and a complicated process, and a capsule-type material that forms an inorganic material as a shell can be synthesized by a colloidal polymer template, but the synthesis conditions are very difficult. .

On the other hand, it is known that it is very difficult for the base wall to retain mesoporous properties while maintaining a hollow capsule with an empty inside of the capsule. Typically, a method using a mold in which a surfactant is aggregated in a solvent has been used. Recently, emulsion synthesis has also been used, in which small droplets to be emulsified act as the molds of hollow capsules and columnar micelles act as the molds for mesoporous base walls. In general, these materials vary in the size of the emulsion formed into the template, so the resulting capsule-like material is synthesized in various sizes. In addition, in the case of using the manufactured hollow capsule as a drug delivery material, since the wall has mesoporosity, it is difficult to pass the drug to be delivered through the wall or to restrict the removal of the manufactured wall. However, there is a problem that it is difficult to contain the delivery material in the capsule inner space, and also difficult to control the delivery material release under a specific environment. Furthermore, since the materials used in the manufacture of molds are used in combination with high-toxic surfactants and polymer polymers in an appropriate ratio, they have a critical limitation in application in areas where cytotoxicity is important, such as biosensors or drug delivery. .

Therefore, the problem to be solved by the present invention is to have a macroporosity and high surface area characteristics, easy to support the material in the hollow, and to simplify the difficult conditions required for the synthesis of nanoparticles in the conventional capsule form without a separate pretreatment process synthesis time It is to provide a hollow mesoporous silica capsule capable of mass production through a single axis and a method of manufacturing the same.

In order to achieve the first object of the present invention,

Mesoporous silica base walls; And it provides a hollow mesoporous silica capsule comprising one or more macropores formed on the silica base wall.

According to one embodiment of the invention, the average diameter of the capsule may be 20nm to 1㎛.

According to another embodiment of the present invention, the average diameter of the macropores may be 1nm to 500nm.

According to another embodiment of the present invention, the cancer cell specific binding peptide sequence or vitamin compound may be attached to the outer surface of the silica base wall through an organic functional group.

According to another embodiment of the present invention, the cancer cell specific binding peptide sequence is Arg-Gly-Asp, and the vitamin compound may be folic acid.

In order to achieve the second object of the present invention,

(a) dissolving a surfactant having Formula 1 in a hydrophilic solvent;

R ₁ R ₂ R ₃ R ₄ NX

Wherein R ₁ , R ₂ and R ₃ are the same as or different from each other CH ₃ -or CH ₂ CH _3- , R ₄ is an alkyl group having 12 to 22 carbon atoms, and X is an anion.

(b) mixing and reacting a silica precursor with the solution prepared in step (a);

(c) cooling the reaction mixture and then filtering to recover the product;

(d) washing and drying the product; And

(e) it provides a method for producing a hollow mesoporous silica capsule comprising the step of firing the dried material.

According to an embodiment of the present invention, the steroid compound may be further added in the step (a).

According to another embodiment of the present invention, the silica precursor substituted with the organic functional group in step (b) may be further added.

According to another embodiment of the present invention, the silica precursor substituted with the organofunctional group is 3-aminopropyltrimethoxysilane, 3-cyanopropyltriethoxysilane, N-2- (aminoethyl) -3-amino Propyltrimethoxysilane, consisting of 3- [2- (2-aminoethylamino) ethylamino] propyltrimethoxysilane, ureidopropyltrimethoxysilane and 3-isocyanoetherpropyltriethoxysilane It may be one or more compounds selected from the group.

According to another embodiment of the present invention, the reaction temperature of step (b) may be 80 ℃ to 100 ℃.

According to another embodiment of the present invention, the mixing mole ratio of the surfactant and the hydrophilic solvent may be 1: 100 to 1: 20,000.

According to another embodiment of the present invention, the mixing molar ratio of the surfactant and the steroid compound may be 1: 0.05 to 1: 0.50.

According to another embodiment of the present invention, the hydrophilic solvent may be an aqueous solution containing distilled water or alcohol having 1 to 2 carbon atoms.

According to another embodiment of the present invention, the firing temperature of step (e) may be 300 ℃ to 800 ℃.

Hollow mesoporous silica capsules according to the present invention have macroporosity and high surface area characteristics, and can easily support enzymes, proteins, various drugs, and other biomaterials having a relatively large size in the hollow, so that the carriers of enzymes and catalysts, In addition, it is possible to exert optimal performance as a drug delivery system, and it is easy to introduce various proteins and vitamin compounds into mesoporous walls, thereby greatly improving the utilization in the field of drug delivery system or biosensor. In addition, according to the method for manufacturing a hollow mesoporous silica capsule according to the present invention, it is possible to support various sizes of biomaterials that can penetrate into cells without a separate pretreatment process, which is required for synthesizing nanoparticles in a conventional capsule form. It is possible to mass-produce by reducing the synthesis time by simplifying the difficult conditions.

Hereinafter, the present invention will be described in more detail.

The first object of the present invention is a mesoporous silica base wall; And hollow mesoporous silica capsules comprising one or more macropores formed on the silica base wall.

1 shows a transmission electron microscope photograph of one hollow mesoporous silica capsule particle according to the present invention. As can be seen from FIG. 1, the capsule includes a hollow capsule including an inner space surrounded by a silica base wall. It can be seen that the wall is composed of mesoporous pores which have a shape, in particular while maintaining a spherical shape.

2 shows a scanning electron micrograph and a transmission electron micrograph of a plurality of hollow mesoporous silica particles prepared according to an embodiment of the present invention, and a schematic diagram of one particle is shown. As can be seen from Figure 2, the hollow mesoporous silica capsule according to the present invention, unlike conventional mesoporous capsules, includes one or more macropores formed on the mesoporous base wall in addition to the general mesoporous base wall. The presence of such macropores in the capsule according to the present invention is a structure adopted to effectively overcome the problem of passage of the delivery material, which is a representative limitation of the conventional mesoporous capsules in the field of drug delivery, in the present invention through such macropores Since the drug to be delivered can be effectively carried in the capsule, it is possible to solve the problem of the mesoporous capsule according to the prior art.

On the other hand, the average diameter of the hollow mesoporous capsule according to the present invention can be variously changed depending on the type and content of the material to be delivered, but is not limited thereto, it may have a value in the range of 20nm to 1㎛. If the average diameter is less than 20nm, there is a problem that the capsule according to the present invention is not suitable for supporting various delivery materials to be delivered, that is, enzymes, proteins, various drugs, and other biomaterials having a relatively large size. Even if it exceeds the size of the capsule is too large to limit the various biological applications, such as intracellular mass transfer is not preferred because there is a problem.

The average diameter of the macropores formed in the hollow mesoporous capsule according to the present invention may have a suitable size for the carrying of the nanoparticles and the passage of the transfer material, but is not limited thereto, and may be 1 nm to 500 nm. When the average pore size of the macropores is less than 1 nm, there is a problem in that it is not easy to pass the material through the macropores from the outside of the capsule to the inside of the capsule, and when it exceeds 50 nm, the material contained in the capsule is easily recapsulated through the macropores. It is not preferable because there is a problem that is emitted to the outside.

On the other hand, the outer surface of the silica base wall forming the hollow mesoporous capsule according to the present invention, that is, the surface facing toward the outside of the capsule, an organic functional group for attaching a peptide sequence or vitamin compound or the like specifically binding to specific cancer cells, etc. It can also be attached using a chemical reaction. The peptide sequence may include, but is not limited to, an Arg-Gly-Asp peptide sequence that binds strongly to α _ν β ₃ integrin and the like, which are overexpressed in specific cancer cells, and the vitamin compounds may recognize specific cancer cells. Folic acid, which may be mentioned.

The second object of the present invention,

(a) dissolving a surfactant having Formula 1 in a hydrophilic solvent;

[Formula 1]

R ₁ R ₂ R ₃ R ₄ NX

Wherein R ₁ , R ₂ and R ₃ are the same as or different from each other CH ₃ -or CH ₂ CH _3- , R ₄ is an alkyl group having 12 to 22 carbon atoms, and X is an anion.

(b) mixing and reacting a silica precursor with the solution prepared in step (a);

(c) cooling the reaction mixture and then filtering to recover the product;

(d) washing and drying the product; And

(e) is achieved by a process for the preparation of hollow mesoporous silica capsules comprising calcining the dry matter.

The method for producing hollow mesoporous silica capsules according to the present invention is synthesized by dissolving a cationic surfactant in a hydrophilic solvent and then adding a silica precursor under predetermined temperature conditions. After the sol-gel reaction is performed by applying heat for a predetermined time, the solid substance precipitated in the solution is filtered, washed sufficiently with distilled water, and then dried, and the dried product is heated in air to remove the organic substances contained therein. Phosphorus hollow mesoporous silica capsules can be obtained.

The surfactant used in the hollow mesoporous silica capsule according to the present invention is a cationic surfactant, which is represented by the following formula (1);

[Formula 1]

R ₁ R ₂ R ₃ R ₄ NX

Wherein R ₁ , R ₂ and R ₃ are the same as or different from each other CH ₃ -or CH ₂ CH _3- , R ₄ is an alkyl group having 12 to 22 carbon atoms, and X is an anion.

Specific examples of the cationic surfactants include dodecyltrimethylammonium hydroxide, tetradecyltrimethylammonium hydroxide, hexadecyltrimethyl ammonium hydroxide, and octadecyltrimethylammonium hydroxide, and octadecyltrimethylammonium hydroxide. Docosyltrimethylammonium hydroxide, icosyltrimethylammonium hydroxide, hexadecyltrimethylammonium hydroxide, and the like. In addition, X may be various anions such as Cl ⁻ , Br ⁻ , OH ⁻ and the like as a counterion of the surfactant. On the other hand, the mixing molar ratio of the surfactant and the hydrophilic solvent may be 1: 100 to 1: 20,000, if the surfactant is added in an excessively small amount out of the molar ratio range it is difficult to form mesopores in the capsule base wall In addition, when added in excess, there is a problem that the base wall of the silica material is formed too thin, which is not preferable.

In the method according to the present invention, the surfactant is used dissolved in a hydrophilic solvent, the hydrophilic solvent is an example of distilled water or an aqueous solution containing an alcohol having 1 to 2 carbon atoms, such as ethanol, methanol and the like.

Preferably, the steroid compound may be further added to the surfactant solution, and the added steroid compound plays a role in inducing the formation of a capsule form in the reaction, and the amount of the steroid compound is added to the surfactant and the steroid compound. The mixing mole ratio of can be adjusted to 1: 0.05 to 1: 0.50. When the steroid compound is added in an excessively small amount outside the molar ratio range, there is a problem in that non-capsule-type particles filled inside, that is, general particles having no hollow, are formed, and in the case of being added in excess, the pore-forming action of the surfactant It is not preferable because there is a problem that disturbs.

Next, the silica precursor is mixed and reacted with the surfactant solution. As the silica precursor, various silica precursors such as tetraethoxysilane may be used, and the reaction temperature may be 80 ° C to 100 ° C. If the reaction temperature is less than 80 ℃, there is a problem that the condensation reaction for the formation of silica is not completed, if the reaction temperature is higher than 100 ℃ because the reaction is carried out in a hydrophilic solvent, the actual temperature of the solution does not rise any more and does not overheat It is not preferable because there is a problem that will cause a reaction. Therefore, when the reaction is to be carried out at a temperature exceeding 100 ℃ must be carried out a hydrothermal reaction using a high pressure reactor.

Meanwhile, according to a preferred embodiment of the present invention, in addition to the silica precursor, a silica precursor substituted with an organic functional group may be further added. As a result, the cancer cell specific binding peptide sequence or vitamin may be added to the outer surface of the silica base wall as a result. It is possible to form an organic functional group for attaching the same kind of compound. Examples of the silica precursor substituted with the organic functional group include, but are not limited to, 3-aminopropyltrimethoxysilane, 3-cyanopropyltriethoxysilane, N-2- (aminoethyl) -3-aminopropyltri Methoxysilane, 3- [2- (2-aminoethylamino) ethylamino] propyltrimethoxysilane, ureidopropyltrimethoxysilane, and 3-isocyanoeitopropyltriethoxysilane One or more compounds may be used.

The reaction mixture is then cooled and filtered to recover the product, the product obtained is washed and dried, and finally the dried product is calcined to produce a hollow mesoporous silica capsule according to the present invention. In the final firing step, the firing temperature is preferably 300 ° C to 800 ° C. When the firing temperature is less than 300 ° C, there is a problem in that the removal of the organic template is not completely performed. It is not preferable because it may collapse.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the scope of the present invention should not be construed as being limited by the following Examples.

Example 1 Preparation of Hollow Mesoporous Silica Capsules According to the Present Invention

1.0 g of cetyltrimethylammonium bromide, 3.5 mL of 2.0 M NaOH, 400 g of distilled water, and 0.25 g of cholesterol were stirred at 80 ° C. at a constant speed of 750 rpm for 40 minutes to mix well. 5 mL of tetraethoxysilane (TEOS) was rapidly added to the stirred solution while maintaining the stirring state, followed by further stirring at 80 ° C. and 750 rpm for 2 hours. The obtained solid substance was filtered under reduced pressure using a filter, and then washed with excess water. The washed material was dried in an 80 ° C. oven for 24 hours, and the obtained solid was heated in a furnace to 550 ° C. at a constant rate of 100 ° C./20 min, and then further heated for 5 hours to remove organics. Hollow mesoporous silica capsules were prepared.

Example 2 Preparation of Hollow Mesoporous Silica Capsules According to the Present Invention

1.0 g of cetyltrimethylammonium bromide, 3.5 mL of 2.0 M NaOH, 400 g of distilled water, and 0.25 g of cholesterol were stirred at 80 ° C. at a constant speed of 750 rpm for 40 minutes to mix well. 5 mL of tetraethoxysilane (TEOS) and 0.47 mL of 3-aminopropyltrimethoxysilane (APTMS) were rapidly added to the stirred solution while maintaining the stirring state, followed by further stirring at 80 ° C. and 750 rpm for 2 hours. . The obtained solid substance was filtered under reduced pressure using a filter, and then washed with excess water. The washed material was dried in an 80 ° C. oven for 24 hours and a mixture of 1.0 g of solid product obtained, 1.0 mL of concentrated hydrochloric acid and 100 mL of methanol was stirred at 60 ° C. at 750 rpm for 6 hours to remove the cationic template. The obtained solid product was filtered under reduced pressure again using a filter, and then washed with excess water. The hollow mesoporous silica capsules according to the invention were prepared by drying the washed material in an 80 ° C. oven for 24 hours.

Example 3 Preparation of Hollow Mesoporous Silica Capsules According to the Present Invention

1.0 g of cetyltrimethylammonium bromide, 3.5 mL of 2.0 M NaOH, 400 g of distilled water, and 0.25 g of cholesterol were stirred at 80 ° C. at a constant speed of 750 rpm for 40 minutes to mix well. 5 mL of tetraethoxysilane (TEOS) and 0.67 mL of cyanopropyltriethoxysilane (CPTES) were rapidly added to the stirred solution while maintaining the stirring state, followed by further stirring at 80 ° C. and 750 rpm for 2 hours. It was. The obtained solid substance was filtered under reduced pressure using a filter, and then washed with excess water. The washed material is dried in an 80 ° C. oven for 24 hours, and a mixture of 1.0 g of solid product and 120 mL of concentrated sulfuric acid is 750 rpm at 95 ° C. for 24 hours for cationic template removal and conversion of cyano functional groups to carboxylic acid functional groups. Stirred. The obtained solid product was filtered under reduced pressure again using a filter, and then washed with excess water. The hollow mesoporous silica capsules according to the invention were prepared by drying the washed material in an 80 ° C. oven for 24 hours.

Experimental Example 1. Intracellular delivery experiment of hollow mesoporous silica capsules according to the present invention

As a kind of polyaminocarboxylic acid, 1 mg of Fura-2 having the following Formula 2 and having the property of binding to intracellular calcium was dissolved in 1.0 mL of pH 7.4 PBS buffer. 3 mg of the hollow mesoporous silica capsule prepared in Example 1 was added to the buffer solution, and stirred for 30 minutes using a stirring device. After centrifugation at 13,000 rpm for 10 minutes, the supernatant was carefully decanted and the solid material obtained was dried in air. Delivery experiments into HeLa cells were performed by dispersing the dried solid material as described above again in 0.5 mL of pH 7.4 PBS buffer.

Experimental Example 2 Intracellular Delivery Experiment of Hollow Mesoporous Silica Capsules According to the Present Invention

Intracellular delivery experiments were performed by the same method as Experimental Example 1, except that the mesoporous silica capsules prepared in Example 2 were used.

FIG. 3 shows a schematic diagram of a drug delivery system in which Fura-2 is loaded into a hollow mesoporous silica capsule prepared in Examples 1 and 2 and delivered into cells. Fura-2 is a compound whose fluorescence varies depending on the concentration of intracellular calcium ions and is widely used as a sensor material for measuring the concentration of intracellular calcium ions. It is known that the negative charge of is very difficult to pass through the hermetic cell membrane. Therefore, Fura-2 is widely used in drug delivery systems as a representative example of a compound that is difficult to penetrate cell membranes.

4 is a fluorescence image observed through a fluorescence microscope after supporting the Fura-2 in the hollow mesoporous silica capsule prepared in Example 1, and transferred it into HeLa cells. Intracellular nuclei were stained with Hoechst Dye. Specifically, in FIG. 4, three photographs labeled 'None' located at the top are photographs observed when Fura-2 is supplied to a cell sample without using a mesoporous silica capsule, and labeled as 'Fura2-565C'. The six photographs in the middle and the six photographs at the bottom are photographs observed when the Fura-2 was loaded using a mesoporous silica capsule according to the present invention and then supplied to a cell sample (six intermediate photographs). And the bottom six pictures are pictures of different areas of the same sample). In addition, the five pictures in the left column labeled 'Fura2-565C' are taken under the wavelength for Fura-2 observation, and the five pictures in the middle column labeled 'Hoechst' are taken under the wavelength for Hoechst observation. The five photos in the right column, labeled 'Merged', are the overlapping photos of the left and middle rows, respectively.

From FIG. 4, it can be seen that the silica capsule (marked as Aggregated particles in the figure) in which the particles are largely aggregated does not penetrate into the cells at all, and the silica capsule in such a state is separated and used only by the supernatant by centrifugation. Simply removable The fluorescence of Fura2-565C shown in FIG. 4 shows that the mesoporous silica capsules according to the present invention have excellent efficacy as drug delivery materials.

FIG. 5 is a fluorescence image observed through a fluorescence microscope after supporting Fura-2 in a mesoporous silica capsule in which the base wall surface is modified with an amino functional group according to Example 2, and transferred into HeLa cells. In this case, a separate staining process was not performed for the intracellular nucleus. Specifically, the two left columns are photographs obtained under the wavelength for Fura-2 observation, and the two right columns are photographs obtained by observing the same region of the same sample under an optical microscope, and the fluorescence part is the cells. These are pictures confirming that. In addition, the upper two photographs are photographs obtained when only Fura-2 was supplied to the cell sample without using mesoporous silica capsules, and the two photographs located at the bottom designated as 'LSJ005B-Fura2' are walled according to the present invention. The photographs were observed when Fura-2 was loaded on a surface using a mesoporous silica capsule modified with an amino functional group and then supplied to a cell sample.

5, when only Fura-2 was supplied to the cell sample, it could be seen that Fura-2 did not penetrate into the cell and thus no fluorescence image appeared. In addition, the fact that the capsules prepared according to Example 2 changes the zeta potential of the capsules by amino functional groups, which facilitates the passage of cell membranes, and thus has better drug delivery efficacy than the capsules prepared according to Example 1 It can be seen.

FIG. 6 is a fluorescence image observed through multiphoton confocal fluorescence microscopy for the experiment under the same conditions as in FIG. 5 (Z-stack: 1 μm). Confocal fluorescence microscopy can be used to observe the cut plane located at a certain distance after obtaining an image from the outside of the cell, Figure 6 is a series of images measured while giving a constant height change (1 ㎛) inside the cell, It can be clearly seen that the mesoporous silica capsule material delivered from 6 is present inside the cell and not outside the cell.

1 is a transmission electron microscope photograph of one hollow mesoporous silica capsule particle according to the present invention.

FIG. 2 is a schematic diagram of a scanning electron micrograph, a transmission electron micrograph, and one particle of a plurality of hollow mesoporous silica particles prepared according to an embodiment of the present invention.

FIG. 3 is a schematic diagram of a drug delivery system in which Fura-2 is loaded into a hollow mesoporous silica capsule prepared in Examples 1 and 2 and delivered into cells. FIG.

FIG. 4 is a fluorescence image photograph of Fura-2 loaded in a hollow mesoporous silica capsule prepared according to Example 1 and transferred to HeLa cells, followed by fluorescence microscopy.

FIG. 5 is a fluorescence image photograph of Fura-2 loaded on a mesoporous silica capsule in which the base wall surface is modified with an amino functional group, and transferred to HeLa cells, followed by fluorescence microscopy.

FIG. 6 is a fluorescence image photograph of data of an experiment under the same conditions as in FIG. 5 observed through a multiphoton confocal fluorescence microscope. FIG.

Claims (14)

Mesoporous silica base walls; And one or more macropores formed on the silica base wall. The hollow mesoporous silica capsule according to claim 1, wherein the capsule has an average diameter of 20 nm to 1 μm. The hollow mesoporous silica capsule according to claim 1, wherein the average diameter of the macropores is 1 nm to 500 nm. The hollow mesoporous silica capsule of claim 1, wherein a cancer cell specific binding peptide sequence or a vitamin compound is attached to an outer surface of the silica base wall through an organic functional group. The hollow mesoporous silica capsule according to claim 4, wherein the cancer cell specific binding peptide sequence is Arg-Gly-Asp, and the vitamin compound is folic acid. (a) dissolving a surfactant having Formula 1 in a hydrophilic solvent; [Formula 1] R ₁ R ₂ R ₃ R ₄ NX Wherein R ₁ , R ₂ and R ₃ are the same as or different from each other CH ₃ -or CH ₂ CH _3- , R ₄ is an alkyl group having 12 to 22 carbon atoms, and X is an anion. (b) mixing and reacting a silica precursor with the solution prepared in step (a); (c) cooling the reaction mixture and then filtering to recover the product; (d) washing and drying the product; And (e) The method of producing a hollow mesoporous silica capsule comprising the step of firing the dried material. The method of claim 6, wherein the method further comprises adding a steroid compound in the step (a). The method of claim 6, wherein the method further comprises adding a silica precursor substituted with an organic functional group in the step (b). The silica precursor substituted with the organofunctional group is 3-aminopropyltrimethoxysilane, 3-cyanopropyltriethoxysilane, N-2- (aminoethyl) -3-aminopropyl trimethoxy. One or more selected from the group consisting of silane, 3- [2- (2-aminoethylamino) ethylamino] propyltrimethoxysilane, ureidopropyltrimethoxysilane, and 3-isocyanoeitopropyltriethoxysilane Method for producing a hollow mesoporous silica capsule, characterized in that the compound. The method of claim 6, wherein the reaction temperature of the step (b) is 80 ℃ to 100 ℃ manufacturing method of hollow mesoporous silica capsules. The method of claim 6, wherein the mixing molar ratio of the surfactant and the hydrophilic solvent is 1: 100 to 1: 20,000. The method according to claim 7, wherein the mixing molar ratio of the surfactant and the steroid compound is 1: 0.05 to 1: 0.50. The method of claim 6, wherein the hydrophilic solvent is a hollow mesoporous silica capsule manufacturing method characterized in that the aqueous solution containing distilled water or an alcohol having 1 to 2 carbon atoms. The method of claim 6, wherein the firing temperature of the step (e) is 300 ℃ to 800 ℃ characterized in that the manufacturing method of hollow mesoporous silica capsules.

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