KR101852153B1 - Method for preparing metal-liposome hybrid structure via a programming technique and metal-liposome hybrid structure prepared thereby - Google Patents
Method for preparing metal-liposome hybrid structure via a programming technique and metal-liposome hybrid structure prepared thereby Download PDFInfo
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- KR101852153B1 KR101852153B1 KR1020160027791A KR20160027791A KR101852153B1 KR 101852153 B1 KR101852153 B1 KR 101852153B1 KR 1020160027791 A KR1020160027791 A KR 1020160027791A KR 20160027791 A KR20160027791 A KR 20160027791A KR 101852153 B1 KR101852153 B1 KR 101852153B1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
- A61K49/0076—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form dispersion, suspension, e.g. particles in a liquid, colloid, emulsion
- A61K49/0084—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form dispersion, suspension, e.g. particles in a liquid, colloid, emulsion liposome, i.e. bilayered vesicular structure
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
- A61K49/1806—Suspensions, emulsions, colloids, dispersions
- A61K49/1812—Suspensions, emulsions, colloids, dispersions liposomes, polymersomes, e.g. immunoliposomes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/04—Metals or alloys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/02—Inorganic materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/02—Inorganic materials
- A61L31/022—Metals or alloys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
- A61L2300/626—Liposomes, micelles, vesicles
Abstract
A metal precursor or a reducing agent is provided to the outside of the liposome to diffuse the liposome into the liposome, and then metal particles are selectively synthesized inside the liposome, so that the liposome forms an outer skeleton of the metal particle To produce a metal-liposome complex structure. Accordingly, a metal-liposome complex structure having a constant size and shape can be produced with high yield.
Description
The present specification relates to a method for producing a metal-liposome complex structure using a programming technique and a metal-liposome complex structure thus produced.
The metal nanostructure has the effect of amplifying the electromagnetic field around the metal nanostructure by interacting with light of a specific wavelength incident from the outside and condensing the light. In particular, in the field of biomedicine, development of in vivo imaging, monitoring and treatment technologies using such metal nanostructures has been widely used in various fields such as catalysts, molecular detection, and solar energy condensing devices, .
However, conventionally prepared metal nanostructures are not easy to exist in the original state because they are not stable in a complex environment such as a living body in which a high concentration of electrolytes and numerous biomolecules exist in a living body in vivo application, It was difficult to maintain.
In addition, the delivery efficiency into the cells is greatly deteriorated, making it difficult to monitor the imaging of the target cell or the intracellular molecular reaction.
In order to solve such a problem, there has been reported a technique of forming a complex structure in which a substance such as a liposome is bonded to the outside of the metal nanostructure.
However, according to the research results of the present inventors, in the case of the previously reported techniques, a method of bonding liposomes to pre-fabricated metal nanoparticles is used, whereby the production of the complex structure is randomized and the reproducibility and the yield are greatly reduced. In addition, there is a problem that the size and shape of the manufactured composite structure are not uniform, so that the application is very limited.
In an exemplary embodiment of the present invention, in one aspect, there is provided a method for producing a metal-liposome complex structure capable of producing a metal-liposome complex structure having a constant size and shape at a high yield, and a method for producing a metal- .
In exemplary embodiments of the present invention, there is provided a method comprising: forming a programmed liposome pre-loaded with a reducing agent or a metal precursor; Providing a metal precursor or reducing agent outside the programmed liposome so that the metal precursor or reducing agent diffuses into the programmed liposome; And a metal-liposome complex structure in which metal particles are synthesized inside a liposome programmed from a reducing agent or a metal precursor supported inside a liposome programmed with a metal precursor or a reducing agent diffused into the programmed liposome, thereby forming the outer skeleton of the metal particle The method comprising the steps of: preparing a metal-liposome complex structure;
In an exemplary embodiment, the preparation method may further comprise organic molecules in the substance to be supported in the liposome. In addition, organic molecules may be further included in the substance transferred from the external environment.
In an exemplary embodiment, the programmed liposome forming step separates the programmed liposome after the reductant or metal precursor has been pre-loaded into the programmed liposome, and then programmed to adjust at least one of size or shape.
In an exemplary embodiment, the programmed liposome forming step comprises the steps of forming a liposome from a lipid membrane in a solution containing a reducing agent or a metal precursor to form a programmed liposome in which a reducing agent or a metal precursor is supported within the liposome; And separating and filtering the liposomes programmed to modulate one or more of the size or shape of the programmed liposomes from a solution comprising the programmed liposomes.
In an exemplary embodiment, the lipids that form the liposome may comprise neutral, negative charge, positive charge. In addition, the number of carbon atoms forming the skeleton may be 10 to 30.
In an exemplary embodiment, the size of the liposome may be 10 [mu] m or less, e.g., 30 nm to 100 nm, or 100 nm or more and 10 [mu] m or less.
In an exemplary embodiment, the liposome form may comprise spherical, rod-shaped, bundled.
In an exemplary embodiment, the metal precursor may be a precursor of metals consisting of, for example, Ag, Au, Cu, Pt, Al, Fe, Co, Ni, Ru, Rh and Pd.
In one exemplary embodiment, the reducing agent may be an organic reducing agent or an inorganic reducing agent and may include, for example, sodium citrate, hydroxyamine, ascorbic acid, sodium borohydride, can do.
In an exemplary embodiment, the organic molecule may include one or more selected from the group consisting of DNA, RNA, fluorescent substance, Raman molecule, nucleic acid, protein.
In exemplary embodiments of the present invention, there is also provided a metal-liposome complex structure, wherein the liposome forms an external skeleton, and metal particles and a reducing agent are present therein.
According to exemplary embodiments of the present invention, a liposome chemical reactor in which a reducing agent or a metal precursor is preliminarily impregnated is prepared instead of a method of previously preparing metal particles and bonding the liposome to the surface, By synthesizing the particles, the metal-liposome complex structure having a constant size and shape can be produced at a remarkably high yield, unlike the prior art.
The metal-liposome complex thus produced forms a metal skeleton of the metal particle at the same time as the metal particle production. The metal particle and the reducing agent used for reducing the metal precursor exist in the liposome at the same time, and a high concentration of electrolyte It can provide high stability and improved intracellular delivery efficiency even in a complex environment such as in vivo in which a large number of biomolecules are present. Such a metal-liposome complex structure can be utilized in various fields such as biomedical, catalytic, and energy fields.
1 is a schematic view showing a process for producing a metal-liposome complex structure in an embodiment of the present invention.
FIG. 2 is a transmission electron microscope image of a liposome carrying a reducing agent or a metal precursor according to an embodiment of the present invention. FIG.
FIG. 3 is a transmission electron micrograph of a metal-liposome complex nanostructure formed by synthesizing metal nanoparticles selectively only in a liposome in an embodiment of the present invention.
FIG. 4 is a graph showing the stability of a metal-liposome complex structure produced in a complex environment similar to a living body in an embodiment of the present invention. FIG.
FIG. 4A shows the results of comparing the stability of the metal nanoparticles and the metal-liposome complex structure prepared in the example of the present invention with the previously reported spherical metal nanoparticles and rod-shaped metal nanoparticles under various solution conditions. FIG. And the stability of the metal-liposome complex structure with time.
FIG. 5 is a graph showing the transfer efficiency of the produced metal-liposome complex structure to cells according to an embodiment of the present invention. FIG. 5 is a graph showing an image showing the amount of a structure delivered to a cell qualitatively and quantitatively 5a) and a graph (Fig. 5B).
FIG. 6 illustrates an application technique for intracellular molecule detection and imaging by applying the metal-liposome complex structure to a cell according to an embodiment of the present invention. FIG. 6A is a result of transferring the fabricated metal-liposome complex structure into cells and obtaining Raman signals of specific molecules present in the cells. FIG. 6B is a result of imaging cells based on the Raman signal of the obtained intracellular molecule.
As used herein, the programming technique refers to a technique in which a reducing agent, a metal precursor, and / or an organic molecule or the like is preliminarily supported in a liposome upon liposome formation.
As used herein, nanoparticles or nanostructured nanostructures are used in the conventional definition of the art and may mean, for example, a size of less than 1000 nm. When the metal-liposome complex structure of the present invention is used in vivo, the size of the metal-liposome complex structure may be 100 nm or less to be suitable for in vivo use.
Hereinafter, exemplary embodiments of the present invention will be described in detail.
Conventionally, in the case of a metal liposome complex structure, a method of previously preparing metal particles and bonding liposomes to the surface has been used. According to this conventional method, metal particles adhere to the outer wall of the liposome or metal particles are present between the lipid films of the liposome, and it is very difficult to obtain a form in which the metal particles are supported inside the liposome. Further, when the metal particles are positioned between the lipid membranes of liposomes, they are likely to cause damage to the complex. In addition, the prepared composite has both size and shape, and thus, there is a great restriction on practical application.
In contrast, the present inventors provide an innovative approach to fabricating metal-liposome complex structures using programming techniques.
As previously defined, the programming technique refers to the technique of pre-loading the liposome with a reducing agent or a metal releasing agent. When a reducing agent or a metal precursor is preliminarily supported or programmed to form a predetermined size or shape of a liposome as a chemical reactor and a metal precursor or a reducing agent is provided to the external environment of the liposome, a metal precursor or a reducing agent And diffuses into the liposome. By this diffusion phenomenon, the metal-liposome complex structure in which the metal nanoparticles are synthesized and the liposome becomes the external framework of the metal nanoparticles can be produced by selectively controlling the reduction reaction of the metal precursor within the liposome only. According to the method, unlike the conventional method, since a metal precursor or a reducing agent is loaded on a liposome through a programming technique in advance and then metal particles are formed through a diffusion reaction, the yield of the metal-liposome complex structure is improved Not only the metal is adhered to the lipid membrane of the liposome or the liposome outer wall but can be stably present in the liposome so that the damage of the complex can be prevented and the size and shape of the metal-liposome complex can be uniformly obtained .
In addition, when forming a programmed liposome, various organic molecules are also supported.
1 is a schematic view showing a process for producing a metal-liposome complex structure in an embodiment of the present invention.
As shown in Fig. 1, a lipid bilayer is formed on a glass substrate in a solution containing, for example, a reducing agent or a metal precursor and organic molecules, and a liposome is formed through hydration of the lipid membrane do. Accordingly, at the time of liposome formation, a reducing agent or a metal precursor and organic molecules can be carried in the liposome membrane (this is referred to as programming).
In a non-limiting example, the lipids that form the liposome include neutral, negative charge, positive charge. In addition, the number of carbon atoms forming the skeleton may be 10 to 30.
In a non-limiting example, the metal precursor may be a precursor of metals consisting of, for example, Ag, Au, Cu, Pt, Al, Fe, Co, Ni, Ru, Rh and Pd . This precursor is not limited for example, HAuCl 4, Au (C 5 H 8 O 2) 3, AgNO 3, H 2 PtCl 6, H 2
In a non-limiting example, the reducing agent may use an organic reducing agent or an inorganic reducing agent. In the case of an inorganic reducing agent, it is preferable to use an organic reducing agent since the reducing power is high but the organic molecule may be deformed.
In a non-limiting example, the reducing agent may include sodium citrate, hydroxyamine, ascorbic acid, sodium borohydride.
In a non-limiting example, the organic molecule may comprise one or more organic molecules selected from the group consisting of DNA, RNA, fluorescent materials, Raman molecules, nucleic acids, proteins.
Meanwhile, as described above, the reducing agent or the metal precursor and the liposomes on which the organic molecules are supported, that is, the programmed liposomes, are separated by centrifugation and can be adjusted to have a certain size or shape through filtration. In a non-limiting example, the liposome obtained as described above may have a size within the range of, for example, 10 占 퐉 or less, or 30 nm to 100 nm or 100 nm or more and 10 占 퐉 or less. When it is used in vivo, it is preferably 100 nm or less. On the other hand, when it is intended to be used in vitro, a microsize can be used.
Likewise, the size of the metal particles in the liposome may be, for example, 20 to 100 nm when used in vivo, or micro-sized when used ex vivo.
In a non-limiting example, liposome forms may include spherical, rod-shaped, bundled.
Through the above process, a solution containing a reducing agent or a metal precursor and organic molecules supported therein, that is, a programmed liposome having a certain size can be selectively secured.
Next, a metal precursor or a reducing agent is further introduced into the solution containing the reducing agent or the programmed liposome in which the metal precursor and the organic molecule are supported. Through this process, a metal precursor or a reducing agent is present in the programmed external environment of the liposome, so that the added metal precursor or reducing agent is transferred into the liposome programmed through the diffusion process.
The metal precursor or reducing agent diffused into the programmed liposome causes a reduction reaction through interaction with a reducing agent or a metal precursor previously supported in the liposome. Through this reduction reaction, metal particles are synthesized.
Through such a process, the synthesis reaction of the metal particles selectively proceeds only in the liposome. As a result, the metal-liposome complex structure in which the liposome forms the outer skeleton of the metal nanoparticles can be produced at the same time as the synthesis of the metal nanoparticles.
The metal-liposome complex structure thus obtained is structurally produced by the above-described production method and has the following distinctive features. That is, the obtained metal-liposome complex structure has the outer skeleton of the liposome, and the metal particles and the reducing agent are present therein. According to the conventional production method, since no reducing agent is used, a reducing agent can not exist in the liposome. On the other hand, according to exemplary embodiments of the present invention, there is a structural peculiarity in which a metal particle and a reducing agent used for reducing the metal precursor are present together in the liposome constituting the external skeleton.
Thus, the conventional method of the embodiments of the present invention, that is, a method of programming, that is, a method of synthesizing metal particles in the interior of the metal nanoparticle using a reducing agent or a liposome carrying a metal precursor Liposome complex structure can be adjusted to a certain size and shape and a metal-liposome complex structure having a constant size and shape can be prepared at a remarkably high yield as compared with the conventional method. have.
In addition, the metal-liposome complex structure according to the embodiments of the present invention can be used for the preparation of metal nanoparticles, and at the same time, the liposome forms an outer skeleton of the metal particles and the reducing agent to form complex skeletons such as a high concentration of electrolytes and numerous living biomolecules Can provide high stability in the environment and improved intracellular delivery efficiency.
Accordingly, the metal-liposome complex structure can be widely used in biomedical fields such as real-time monitoring at cell and molecular level, imaging and customized treatment, and other catalysts and energy fields using molecular detection and photo-thermal effect have.
Hereinafter, specific embodiments according to exemplary embodiments of the present invention will be described in more detail. It should be understood, however, that the invention is not limited to the embodiments described below, but that various embodiments of the invention may be practiced within the scope of the appended claims, It will be understood that the invention is intended to facilitate the practice of the invention to those skilled in the art.
Example
≪ Formation of a uniform size liposome carrying a reducing agent or a metal precursor and an organic molecule >
Lipids (eg, 1,2-disteraoyl-sn-glycero-3-phosphocholine (DSPC)) were dissolved in chloroform and the chloroform was completely evaporated using a rotary evaporator To form a lipid thin film. A reducing agent (eg, 300 mM trisodium citrate dehydrate) was dissolved in distilled water and added to the lipid film. Subsequently, the lipid was dissolved while maintaining the temperature at 55-60 ° C (the threshold temperature of the phospholipid), and then the reducing agent was passed through an extruder having various sizes of filters (30 nm, 50 nm, 100 nm and 200 nm) To prepare a liposome having a predetermined size.
The remainder was removed except the pellet which had settled through the centrifuge, and the liposome carrying the reducing agent was selectively secured through repeated washing and centrifugation through distilled water.
FIG. 2 is a transmission electron microscope image of a liposome carrying a reducing agent, according to an embodiment of the present invention. FIG. Figures 2a, 2b, 2c and 2d show liposomes having a constant size of 30, 50, 100 and 200 nm, respectively.
<Introduction of a metal precursor or a reducing agent to the external environment of the formed liposome>
Metal precursors (eg, HAuCl 4 3H 2 O, tetrachloroauric acid trihydrate) were dissolved in distilled water and the pH was controlled to control the ionization state of the metal precursor. When the ionized metal precursor solution and the reducing agent-supported liposome are mixed and reacted at room temperature, the neutralized metal precursor existing only at a specific pH passes through the liposome without destroying the phospholipid membrane. At this time, the diffusion takes place in mm seconds. For reference, the metal precursor can be more effectively transferred into the liposome due to the osmotic effect due to the difference between the salt concentration in the liposome and the external salt concentration.
FIG. 3 is a transmission electron micrograph of a metal-liposome complex nanostructure formed by synthesizing metal nanoparticles selectively only in a liposome in an embodiment of the present invention.
The transmission electron microscope image shows that the liposome forms an outer skeleton around the metal nanoparticles. 3A, 3B, 3C and 3D show metal-liposome complex structures having a constant size of 30, 50, 100 and 200 nm, respectively.
<Metal particle synthesis selectively through reduction reaction in liposome>
The metal precursor delivered to the inside of the liposome (or the reducing agent when the metal precursor is preliminarily supported) selectively reacts with the reducing agent (or metal precursor) supported only inside the liposome. Based on the 100 nm size liposome, the metal precursor delivered into the liposome will form metal particles within the liposome without damage to the phospholipid after 2 hours. When the reaction is performed after 12 hours, the inside of the liposome is completely filled with the metal particles, and naturally, the liposome forms a metal-liposome complex structure constituting the external framework.
FIG. 4 is a graph showing the stability of a metal-liposome complex structure fabricated in a complex environment similar to that in a living body according to an embodiment of the present invention. FIG.
Specifically, FIG. 4A shows the stability of the metal-liposome complex structure prepared according to the present invention and the reported spherical metal nanoparticles and rod-shaped metal nanoparticles under various solution conditions. As a result, It can be confirmed that the metal-liposome complex structure produced in the present invention exhibits high stability in various environments as compared with the previously reported metal nanoparticles.
FIG. 4B shows that the stability of the metal-liposome complex structure produced under various solution conditions is stable over time after one month as a result of showing stability over time.
FIG. 5 shows the efficiency of the produced metal-liposome complex structure into cells in an embodiment of the present invention.
5A and 5B are images and graphs showing qualitatively and quantitatively the amount of the structure transferred into the cell by measuring the scattering intensity, respectively. Compared with the previously reported spherical metal nanoparticles, the metal-liposome complex has a higher intracellular Transfer efficiency .
FIG. 6 illustrates an application technique for intracellular molecule detection and imaging by applying the metal-liposome complex structure to a cell according to an embodiment of the present invention.
Specifically, FIG. 6A is a result of transferring the produced metal-liposome complex into cells and obtaining Raman signals of specific molecules present in the cells. FIG. 6B is a result of imaging cells based on the Raman signal of the obtained intracellular molecule.
As can be seen from the results, the metal-liposome complex structure according to the exemplary embodiments of the present invention is a liposome that forms an outer skeleton and serves as a protective film, And the like. In addition, the size and shape can be kept constant by this, and the original function can be smoothly performed.
Claims (19)
The method comprising: providing a metal precursor HAuCl 4 3H 2 O outside the programmed liposome and adjust the pH of the neutralized state metal precursor to diffuse into the liposomes; And
(Au) particles are synthesized by reducing the metal precursor within the programmed liposome from the metal precursor diffused into the programmed liposome and the reducing agent supported inside the programmed liposome to form a liposome, Preparing a metal-liposome complex structure comprising the metal-liposome complex structure.
Wherein the programmed liposome forming step separates the programmed liposome after the reducing agent is pre-loaded, and then the programmed liposome is adjusted so that at least one of size or shape is controlled.
Wherein the programmed liposome forming step comprises: forming a liposome from a lipid membrane in a solution containing the reducing agent to form a programmed liposome in which the reducing agent is supported inside the liposome; And
Separating and filtering the liposomes programmed to adjust one or more of the size or shape of the programmed liposomes.
Wherein the liposome-forming lipid comprises neutral, negative charge or positive charge.
Wherein the liposome-forming lipid comprises 10 to 30 carbon atoms forming the skeleton.
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| KR1020160027791A KR101852153B1 (en) | 2016-03-08 | 2016-03-08 | Method for preparing metal-liposome hybrid structure via a programming technique and metal-liposome hybrid structure prepared thereby |
| PCT/KR2017/002485 WO2017155293A2 (en) | 2016-03-08 | 2017-03-08 | Method for producing metal-liposome complex structure using programming technique, and metal-liposome complex structure produced thereby |
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| DE19721601A1 (en) * | 1997-05-23 | 1998-11-26 | Hoechst Ag | Polybetain-stabilized, palladium-containing nanoparticles, a process for their production and catalysts made therefrom for the production of vinyl acetate |
| WO2003091159A1 (en) * | 2002-04-25 | 2003-11-06 | General Electric Company | Preparation of nanosized copper (i) compounds |
| KR101174470B1 (en) * | 2010-04-08 | 2012-08-16 | 한국세라믹기술원 | Magnetic silica-liposome nanospheres and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996014165A1 (en) * | 1994-11-04 | 1996-05-17 | The Government Of The United States Of America, Represented By The Secretary Of The Navy | Polymerized phospholipid membrane mediated synthesis of metal nanoparticles |
| JP2010235464A (en) * | 2009-03-30 | 2010-10-21 | Natl Inst Of Radiological Sciences | Therapeutic agent-containing liposome pursuing accumulation and release to target part of therapeutic agent, and method for producing the same |
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| Publication number | Publication date |
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| WO2017155293A3 (en) | 2018-08-02 |
| KR20170104847A (en) | 2017-09-18 |
| WO2017155293A2 (en) | 2017-09-14 |
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