WO2015141876A1 - Graphene oxide nanocomposite exhibiting excellent photothermal effect and manufacturing method therefor - Google Patents

Graphene oxide nanocomposite exhibiting excellent photothermal effect and manufacturing method therefor Download PDF

Info

Publication number
WO2015141876A1
WO2015141876A1 PCT/KR2014/002350 KR2014002350W WO2015141876A1 WO 2015141876 A1 WO2015141876 A1 WO 2015141876A1 KR 2014002350 W KR2014002350 W KR 2014002350W WO 2015141876 A1 WO2015141876 A1 WO 2015141876A1
Authority
WO
WIPO (PCT)
Prior art keywords
graphene oxide
group
nanoparticles
nanocomposite
photothermal
Prior art date
Application number
PCT/KR2014/002350
Other languages
French (fr)
Korean (ko)
Inventor
장의순
윤금희
김보미
조아라
심규동
김다정
한효원
Original Assignee
금오공과대학교 산학협력단
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 금오공과대학교 산학협력단 filed Critical 금오공과대학교 산학협력단
Publication of WO2015141876A1 publication Critical patent/WO2015141876A1/en

Links

Images

Classifications

    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
    • H01F1/00—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties
    • H01F1/0036—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties showing low dimensional magnetism, i.e. spin rearrangements due to a restriction of dimensions, e.g. showing giant magnetoresistivity
    • H01F1/0045—Zero dimensional, e.g. nanoparticles, soft nanoparticles for medical/biological use
    • H01F1/0063—Zero dimensional, e.g. nanoparticles, soft nanoparticles for medical/biological use in a non-magnetic matrix, e.g. granular solids

Definitions

  • the present invention relates to a graphene oxide nanocomposite having excellent light-heating effect and a method of manufacturing the same, and more particularly, the nanocomposite exhibits improved light-heating effect and at the same time has excellent heat conduction effect, and has a high heat release effect.
  • the present invention relates to a graphene oxide nanocomposite having excellent light-heating effect and a method of preparing the same, having a light transmittance, amplifying a light-heating effect, significantly reducing the separation of the nanocomposite, and increasing the separation / collection of the nanocomposite.
  • Graphene has received a lot of attention in science and engineering. This is due to the electrical, optical, thermal and mechanical properties of graphene and their associated carbon nanostructures. Such graphene has been difficult to produce, but has been synthesized through mechanical exfoliation, redox methods, epitaxy growth, and vapor phase deposition. These methods enable the realization of graphene-based materials through the application of nanotechnology, and graphene manufacturing methods such as Korean Patent Application No. 2010-0117206 have been diversified.
  • Graphite has a layered structure in which the graphene layers are stacked in the z-axis direction, and graphite oxide also has a layered structure.
  • the sp 2 network partially breaks into sp 3 bonds, and various oxygen functional groups are bonded through covalent bonds to the top and edge portions of the nanographene.
  • Lerf's model is generally accepted. In general, it is known that a hydroxyl group and an epoxy group exist on the top surface and a carboxyl group and a ketone group exist at the end.
  • the various functional groups as described above serve to disperse the graphene oxide in water and to enable chemical modification.
  • graphene oxide is widely used as a support for nanomaterials due to the large number of functional groups and large areas.
  • Metal nanoparticles mean metal particles having a particle size of 1 to 1000 nm, and have a large specific surface area and a quantum confinement effect in which the energy required for electron transition is changed according to the size of the material. Because of this, they exhibit completely different optical, electrical and magnetic properties than bulk materials. In particular, some metal nanoparticles exhibit photothermal properties, and the photothermal effect refers to an effect of absorbing light and releasing heat. The photothermal effect is known to vary depending on the type, shape and size of the metal nanoparticles, and also depends on the wavelength and intensity of the laser irradiated to the metal nanoparticles.
  • the composite in order to obtain a desired photothermal effect, the composite was made by agglomerating the metal nanoparticles, but in this case, the irradiated light is hardly transmitted to the inside of the composite to prepare for the content of the metal nanoparticles. Sufficient photothermal effect could not be obtained.
  • the aggregated complex is easy to be separated into individual nanoparticles, and the manufacturing process is complicated and expensive, such as encapsulating the composite with a separate material in order to prevent this, and the capsule layer is configured to transfer heat generated inside the capsule to the outside. There was a side effect that prevented the release of heat rather than delivering it.
  • the metal particles expressing the photothermal effect or the composites aggregated thereof have a long manufacturing time and high cost, but they cannot be reused and discarded due to difficulty in separating and collecting them after use.
  • the present invention has been made to solve the above problems, the first problem to be solved by the present invention is to maximize the manifestation of the photothermal effect and at the same time easy to emit the heat generated, and to have a high light transmittance Graphene oxide nanocomposites and methods for producing the same can be further amplified, the separation of nanocomposites is significantly lowered, and the separation / collection of nanocomposites is increased, thereby facilitating reuse and reducing the manufacturing and purchasing costs. To provide.
  • the second problem to be solved by the present invention is to provide a nanocomposite for cancer cell diagnosis and treatment by applying a remarkably excellent photothermal effect, heat release properties and separation / collection of the nanocomposite.
  • the support comprising a graphene oxide (GO) nanosheet; It is included covalently bonded on the graphene oxide nanosheets, the first nanoparticles having a magnetic; And a second nanoparticle covalently bonded to at least one of the graphene oxide (GO) and the first nanoparticle and expressing a photothermal effect.
  • the graphene oxide nanocomposite having excellent photothermal effect is provided.
  • the nanosheet may be a single layer of graphene oxide.
  • the first nanoparticles include a core layer comprising a magnetic material; And a surface of the silica shell layer surrounding the core layer and including any one or more functional groups selected from the group consisting of a thiol group, an amine group, and a carboxyl group.
  • the magnetic material is cobalt (Co), manganese (Mn), iron (Fe), nickel (Ni), gadolinium (Gd), germanium (Ge), aluminum (Al), Molybdenum (Mo), at least one metal material selected from the group consisting of MM ' 2 O 4 and M x O y ; And cobalt-copper (CoCu), cobalt-platinum (CoPt), iron-platinum (FePt), cobalt-samarium (CoSm), nickel-iron (NiFe), and nickel-iron-cobalt (NiFeCo).
  • One or more metal alloys may include any one or more.
  • M or M ' is Co, Mn, Fe, Ni, Gd, Ge, Al, Mo, 0 ⁇ x ⁇ 3, 0 ⁇ y ⁇ 5.
  • the second nanoparticles may be surface-modified photothermal metal nanoparticles including any one or more functional groups selected from the group consisting of a silane group, an amine group and a carboxyl group.
  • the second nanoparticle shape may be rod-shaped.
  • the photothermal metal nanoparticles may include any one or more selected from the group consisting of gold, silver, palladium, platinum, copper and aluminum.
  • the nanocomposite includes a support including a single layer of graphene oxide nanosheets; A first nano-containing core layer comprising a magnetic material containing triiron tetraoxide (Fe 3 O 4 ) and a silica shell layer surrounding the core layer and surface-modified with an amine group and covalently included on the graphene oxide nanosheets. particle; And photothermal metal particles including gold nanorods having an aspect ratio of 3 to 4 whose surface is modified by a silane group, and are covalently bonded to any one or more of the graphene oxide nanosheets and the first nanoparticles. It may include a second nanoparticle.
  • a first nano-containing core layer comprising a magnetic material containing triiron tetraoxide (Fe 3 O 4 ) and a silica shell layer surrounding the core layer and surface-modified with an amine group and covalently included on the graphene oxide nanosheets. particle
  • photothermal metal particles including gold nanorods having an aspect ratio of 3 to 4
  • the nanocomposite may satisfy the following conditions (1) to (3) when irradiating a laser having a wavelength of 780 nm and an intensity of 2 mW / cm 2 .
  • the temperature increased after 100 seconds of laser irradiation is 6 ° C or higher than before laser irradiation
  • the temperature increased after 300 seconds of laser irradiation is 20 ° C or higher than before laser irradiation
  • the laser irradiation 900 After an elapse of time the increased temperature is above 38 ° C compared to before laser irradiation.
  • the present invention (1) preparing a first composite by injecting graphene oxide nanosheets into a solution containing the first nanoparticles having a magnetic; And (2) preparing a second complex by adding the first complex to a solution containing second nanoparticles expressing a photothermal effect, thereby providing a graphene oxide nanocomposite having excellent photothermal effects.
  • the step (1) is one or more functional groups selected from the group consisting of a thiol group, an amine group and a carboxyl group contained on the surface of the silica shell layer of the first nanoparticles on the graphene oxide nanosheets
  • Covalent bonds may be formed between any one or more functional groups selected from the group consisting of thiol groups, amine groups and carboxyl groups.
  • step (2) comprises at least one functional group selected from the group consisting of a thiol group, an amine group and a carboxyl group included in the silica shell layer of the first nanoparticles included in the first composite; And one or more functional groups selected from the group consisting of a thiol group, an amine group, and a carboxyl group included in the graphene oxide nanosheets; Covalent bonds may be formed between any one or more of the functional groups and any one or more functional groups selected from the group consisting of silane groups, amine groups and carboxyl groups on the surface of the photothermal metal nanoparticles.
  • the present invention to solve the above-described second problem, provides a graphene oxide nanocomposite for cancer cell diagnostics comprising a nanocomposite according to the present invention.
  • the present invention also provides a graphene oxide nanocomposite for treating cancer cells, including the nanocomposite according to the present invention.
  • graphene oxide nanosheets refers to a graphene oxide having a thickness of nano units obtained by exfoliating graphite by physical and chemical methods.
  • photothermal metal nanoparticles refers to metal nanoparticles having photothermal characteristics, that is, heat generation depending on light absorption.
  • the nanocomposite of the present invention exhibits an improved photothermal effect and at the same time has excellent thermal conductivity, has an excellent effect of releasing heat, and has a high light transmittance, thereby further amplifying the photothermal effect, and the separation of the nanocomposite is significantly reduced.
  • the durability is excellent, and the separation / collection of the nanocomposites is increased, and thus the reuse is easy, thereby reducing the manufacturing / purchasing cost and it is beneficial in terms of preventing environmental pollution according to resource recycling.
  • FIG. 1 is a schematic diagram of a nanocomposite according to an embodiment of the present invention.
  • Figure 2 is a schematic cross-sectional view of the first nanoparticles according to an embodiment of the present invention.
  • Figure 3 is a schematic diagram of the first nanoparticles covalently bonded on the graphene oxide nanosheets according to an embodiment of the present invention.
  • Figure 4 is a schematic diagram of the second nanoparticles according to an embodiment of the present invention.
  • TEM 5 is a scanning electron microscope (TEM) photograph of graphene oxide included in one preferred embodiment of the present invention.
  • TEM 6 is a scanning electron microscope (TEM) photograph of triiron tetraoxide (a) and the first nanoparticle (b) including the same, included in a preferred embodiment of the present invention.
  • TEM 7 is a scanning electron microscope (TEM) photograph of the second nanoparticles including the gold nanorods included in the preferred embodiment of the present invention.
  • TEM 8 is a scanning electron microscope (TEM) photograph of a composite including only graphene oxide and first nanoparticles according to a comparative example of the present invention.
  • TEM 9 is a scanning electron microscope (TEM) photograph of the graphene oxide nanocomposite according to an embodiment of the present invention.
  • FIG. 11 is a graph showing the temperature per hour when irradiating near infrared laser having a wavelength of 780 nm and an intensity of 2 mW / cm 2.
  • FIG. 12 is a schematic diagram showing a manufacturing process of graphene oxide nanocomposite according to an embodiment of the present invention.
  • the composite of the metal nanoparticles exhibiting the photothermal effect is formed by agglomeration of the metal nanoparticles to obtain the desired photothermal effect, but in this case, the irradiated light is hardly transmitted to the inside of the composite to obtain sufficient photothermal effect.
  • the agglomerated composites could not be easily separated into individual nanoparticles, and a protective film for preventing them had a problem of complicated manufacturing process, high cost, and heat emission.
  • a support comprising a graphene oxide (GO) nanosheets; Covalently bonded to the graphene oxide nanosheets and include magnetic first nanoparticles; And a second nanoparticle covalently bonded to at least one or more of the graphene oxide (GO) and the first nanoparticle, and expressing a photothermal effect.
  • GO graphene oxide
  • a second nanoparticle covalently bonded to at least one or more of the graphene oxide (GO) and the first nanoparticle, and expressing a photothermal effect.
  • Figure 1 is a schematic diagram of a nanocomposite according to an embodiment of the present invention, the graphene oxide nanocomposite is magnetically covalently bonded on the support (1) comprising a graphene oxide (GO) nanosheet
  • the first nanoparticle 2 and the graphene oxide nanosheet 1 and / or the second nanoparticle 3 expressing a photothermal effect covalently bonded with the first nanoparticle 2 may be included.
  • the support 1 including the graphene oxide (GO) nanosheets will be described.
  • the graphene oxide nanosheets serve as a supporter capable of chemically bonding with the first nanoparticles 2 and the second nanoparticles 3, which will be described below, while simultaneously transferring and dissipating heat generated from the second nanoparticles to the outside. And it can express the effect of amplifying the photothermal effect.
  • graphene oxide includes a functional group such as a hydroxyl group, an epoxy group, an carboxyl group, and a ketone group at the surface or the end thereof, and the functional group may be described later.
  • the first nanoparticles (2) and the second nanoparticles (3) may act as a linker capable of chemically bonding to the graphene oxide nanosheets.
  • graphene oxide has a high thermal conductivity of up to 5,000 W / mK is very advantageous compared to the support of other materials in the transfer and release of heat generated.
  • graphene oxide itself has a certain level of photothermal effect, and as a result of expressing light transmittance of up to 97.7%, the reflectance is low when irradiating light such as a laser to further amplify the photothermal effect of the nanocomposite. There is this.
  • reduced graphene oxide (RGO) nanosheets may be undesirable to achieve the object of the present invention.
  • various functional groups such as those described above are reduced, further due to the absence of functional groups capable of chemically bonding with the first nanoparticles 2 and / or the second nanoparticles 3. There may be a problem that makes the bonding of the strong support and the nanoparticles difficult.
  • the nanosheet may preferably be a single layer of graphene oxide, because it is advantageous in the transfer of heat generated as compared to the multilayer case. Specifically, since the graphene oxide of the multi layer includes air between layers, the thermal conductivity may be reduced, and thus, it is preferable to use a single layer of graphene oxide nanosheets to increase heat transfer or release efficiency.
  • the thickness of the graphene oxide nanosheets of such a single layer may be about 0.5 to 3nm, preferably 0.8 to 1.5nm.
  • the area of the graphene oxide nanosheets that may be included in the nanocomposite according to the present invention is an area sufficient to include the first nanoparticles 2 and the second nanoparticles 3, which will be described below, on the nanosheets. If it is, it does not specifically limit, Preferably it may be 0.1-1 micrometer ⁇ 2> .
  • the graphene oxide (GO) nanosheets included in the present invention may be graphene oxide (GO) prepared by a conventional publicly known method, and thus, in the present invention, a method for preparing graphene oxide (GO) It does not specifically limit about.
  • the graphene oxide nanosheets may be manufactured from graphite plaques according to a known modified Hummers method, and the exfoliation process may be performed through ultrasonic irradiation on the prepared graphene oxide nanosheets. Can be prepared.
  • the prepared solution can be filtered using a cellulose acetate membrane having a pore diameter of about 300 to 600 nm, and the filtered solid material is further purified and washed, and then a few drops of 10-12 wt% aqueous hydrochloric acid solution is added.
  • Graphite oxide nanosheets can be prepared by centrifugation and vacuum drying the final product. This specific manufacturing method is one example of manufacturing the graphene oxide nanosheets included in the present invention, but is not limited thereto. Specifically, Figure 5 shows a scanning electron micrograph of the graphene oxide nanosheets prepared by the above method.
  • the first nanoparticles 2 according to the present invention include particles having magnetic properties, they can be easily separated and collected by using a magnetic field even after using the nanocomposites, which is very advantageous in terms of recycling and cost reduction of the nanocomposites.
  • the first nanoparticles 2 includes a core layer including a magnetic material; And a surface of the silica shell layer surrounding the core layer and including any one or more functional groups selected from the group consisting of a silane group, an amine group, and a carboxyl group.
  • FIG. 2 is a schematic cross-sectional view of the first nanoparticles 2 according to an exemplary embodiment of the present invention, in which the first nanoparticles 2 have a silica shell layer surrounding the core layer 2a containing a magnetic material ( As a core shell structure including 2b), an amine group 2c may be included as the surface of the silica shell layer 2b is modified.
  • the diameter of the first nanoparticles 2 is not particularly limited in the present invention, but may be 1 to 100 nm, preferably 1 to 20 nm, except for the amine group 2c.
  • Magnetic nanoparticles may include silica as a shell layer in terms of ease of surface modification, but are not limited thereto, and metals such as silver, gold, and platinum or zinc oxide (ZnO), aluminum oxide (Al 2 O 3 ), and dioxide
  • the shell layer which consists of oxides, such as titanium, can be included.
  • the core layer 2a including the magnetic material may be made of nanoparticles, and may include any magnetic material without limitation.
  • the magnetic material is cobalt (Co), manganese (Mn), iron (Fe), nickel (Ni), gadolinium (Gd), germanium (Ge), aluminum (Al), molybdenum (Mo), MM ' 2 Any one or more metal materials selected from the group consisting of O 4 and M x O y may be used.
  • M or M ' is Co, Mn, Fe, Ni, Gd, Ge, Al, Mo.
  • the magnetic material is made of cobalt-copper (CoCu), cobalt-platinum (CoPt), iron-platinum (FePt), cobalt-samarium (CoSm), nickel-iron (NiFe) and nickel-iron-cobalt (NiFeCo) Any one or more magnetic alloys selected from the group may be used, or two or more of the above-described metal materials and magnetic alloys may be used in combination.
  • the specific shape of the magnetic material is not particularly limited, and may be a sphere, a rod, a star shape, or the like.
  • the magnetic material may be in a form in which one particle and / or several particles are aggregated.
  • the diameter of the magnetic material is not particularly limited, but may be preferably 1 to 100 nm in consideration of ease of manufacture, expression of desired physical properties, and the like. In the case of the diameter, when the shape of the magnetic material is not spherical, it means the maximum distance from one point of the outer surface of the magnetic material to the other point of the outer surface.
  • silica shell layer 2b surrounding the core layer 2a containing the magnetic material will be described.
  • the core layer 2a including the magnetic material described above has a problem that it is difficult to disperse in water and not easy to modify the surface, so that the core layer 2a cannot be easily bonded to the support 1 included in the present invention. Accordingly, the core layer 2a containing the magnetic material is coated with silica to be included as a shell layer so as to be dispersed in water well and to facilitate surface modification, thereby inducing the first nanoparticles around the graphene oxide nanosheets. There is an advantage of increasing the probability of the bonding between the functional groups present on the pin oxide nanosheets and the functional groups on the surface of the first nanoparticles.
  • the thickness of the silica shell layer 2b is not particularly limited as long as it can express sufficient water dispersibility.
  • the thickness of the silica shell layer 2b may be formed to a thickness of 1 to 50 nm, and a specific method of forming the silica shell layer 2b may include the present invention.
  • a well-known technique can be used,
  • a silica shell layer can be formed by a microemulsion method.
  • the magnetic material nanoparticles, the dispersion solvent and ammonia water may be mixed in a volume ratio of 1: 200 to 400: 0.1 to 0.3, and the organic solvent is 10 to 100 parts by weight based on 100 parts by weight of the magnetic material nanoparticles, and silica.
  • the silica shell layer may be prepared by mixing the precursor at 0.01 to 1 part by weight.
  • Specific examples of the silica precursor may be tetramethyl orthosilicate, tetraethyl orthosilicate, tetrabutyl orthosilicate, sodium silicate, sodium metasilicate, or the like, or a mixture of two or more thereof.
  • the method is just one example, and is not limited to this manufacturing method.
  • the surface of the silica shell layer 2b surrounding the core layer 2a including the magnetic material may be modified to include one or more functional groups selected from the group consisting of a thiol group, an amine group and a carboxyl group.
  • a functional group capable of covalently bonding with such a functional group should be included in the graphene oxide.
  • the graphene oxide nanosheet including an amine group is If desired, in the case of a silica shell layer containing a thiol group, a graphene oxide nanosheet including a thiol group may be required, and more specifically, a nanosheet having a thiol group introduced therein may include 2-naphthalene thiol containing a thiol group ( 2-naphthalenethiol), 1,4-benzene dithiol (1,4-benzene dithiol), etc.
  • the amine group 2c may react with the carboxyl group, which is one of the functional groups included on the graphene oxide nanosheet, to form an amide bond, thereby realizing excellent binding force between the first nanoparticle 2 and the support 1. have.
  • Figure 3 is a schematic diagram of the first nanoparticles (2) covalently bonded on the graphene oxide nanosheets 1 according to a preferred embodiment of the present invention, the carboxyl group included in the graphene oxide nanosheets 1 It can be seen that the amide bond is formed in the amine period contained in the surface of the nanoparticles (2).
  • the method of modifying the surface of the silica shell layer 2b with at least one of a thiol group, an amine group and a carboxyl group may use a known method, and firstly, N- (3-acryloxy-2- as a precursor for providing an amine group.
  • carboxyl group may be introduced through a silane compound containing a carboxyl group, and as a non-limiting example, carboxyethylsilanetriol sodium salt, triethoxysilylpropylmaleamic acid or Trimethoxysilylpropylethylene diamine triacetic acid sodium salt (N- (trimethoxysilylpropyl) ethylene diamine triacetic acid trisodium salt) etc. can be used 1 type or in combination of 2 or more types.
  • the thiol group may be provided through a precursor including a thiol-silane group, preferably 3-mercaptopropyltrimethoxysilane, 3-mercaptopropyltriethoxysilane (3- mercaptopropylethoxysilane), 11-mercaptoundecyltrimethoxysilane, mercaptomethylmethyldiethoxysilane, bis [3- (triethoxyl) propyl] -disulfide (Bis [3- (trietoxysilyl) ) Propyl] -disulfide or the like can be used alone or in combination of two or more.
  • a thiol-silane group preferably 3-mercaptopropyltrimethoxysilane, 3-mercaptopropyltriethoxysilane (3- mercaptopropylethoxysilane), 11-mercaptoundecyltrimethoxysilane, mercaptomethylmethyldiethoxy
  • FIG. 6 is a first nanoparticle including ferric tetraoxide nanoparticles (FIG. 6A) and a silica shell layer surrounding the nanoparticles as magnetic material nanoparticles, which are core parts included in a preferred embodiment of the present invention (FIG. 6B). Scanning electron micrographs of shows that the shell layer was formed at a predetermined thickness in the core portion.
  • Figure 4 is a schematic diagram of the second nanoparticles (3) according to an embodiment of the present invention
  • the second nanoparticles (3) includes a photothermal metal (3a) exhibiting a photothermal effect, 3a) may be modified with a silane group 3b, and the photothermal metal 3a may include an organic compound 3c.
  • the second nanoparticles 3 are bonded to the graphene oxide nanosheets as shown in FIG. 1 (in the case of 3 in FIG. 1) or simultaneously bonded to the graphene oxide nanosheets and the first nanoparticles 2 (FIG. 1) may be combined with the first nanoparticle 2 (Q in FIG. 1).
  • the photothermal metal 3a may include any one or more selected from the group consisting of gold, silver, palladium, platinum, copper, and aluminum, and gold may be preferably used in view of photothermal effects.
  • the shape of the photothermal metal 3a is not particularly limited in the present invention, and may be a spherical shape, a rod shape, a star shape, or the like, and preferably may be rod-shaped in terms of light heat effect and ease of manufacture.
  • the diameter of the photothermal metal is not particularly limited in the present invention, and the diameter in the spherical shape and the aspect ratio in the rod shape are related to the wavelength of the laser irradiated to the photothermal metal, thereby to use the nanocomposite according to the present invention.
  • the diameter or aspect ratio of the photothermal metal may be changed.
  • the light-heat metal is gold and the rod type having an aspect ratio of 3 to 4
  • the light-heat effect may be excellent at a wavelength of 780 nm of near infrared rays, and the light-heat effect may be lowered at other wavelengths.
  • Figure 7 can be confirmed the rod-type gold nanorods by scanning electron micrograph of the gold nanorods contained in the second nanoparticles included in the preferred embodiment according to the present invention.
  • the photothermal metal 3a included in the second nanoparticle 3 may include any one or more functional groups selected from the group consisting of a silane group 3b, an amine group, and a carboxyl group.
  • a covalent bond is formed with a functional group such as a hydroxy group, a carboxyl group, and / or a silica shell layer included in the graphene oxide nanosheets and / or an amine group included in the shell layer. You can.
  • the silane group included in the photothermal metal may covalently bond with the hydroxy group and / or carboxyl group included in the graphene oxide nanosheet, and the amine group included in the photothermal metal may form an amide bond with the carboxyl group included in the graphene oxide nanosheet.
  • the carboxyl group included in the photothermal metal may have an amide bond with the amine group included in the graphene oxide nanosheet into which the amine group is introduced.
  • the method of introducing the amine group into the graphene oxide nanosheets may use a known conventional technique and a conventional amine compound used at this time.
  • the silane group included in the photothermal metal may be covalently bonded to the silica shell layer of the first nanoparticles
  • the amine group included in the photothermal metal may have an amide group and a carboxyl group introduced into the silica shell layer of the first nanoparticle
  • the carboxyl group included in the photothermal metal may have an amide bond with the amine group introduced into the silica shell layer of the first nanoparticle.
  • the silane group may be introduced to the surface of the photothermal metal 3a through a precursor including a silane group, and the precursor may be used without limitation in the case of a precursor used when functionalizing a surface of a metal into a silane group.
  • the thiol group of the precursor may be combined with the photothermal metal, through which the photothermal metal surface may be modified with a silane group.
  • a compound containing a thiol group and an amine group is preferable.
  • 2-amino-mercapto-1,3,4-cidazole (2-Amino-5 -mercapto-1,3,4-thiadiazole, Thiaguanine, Cysteine, Penicillamine, 4-Amino-2-mercaptobutyric acid , Cysteamine, etc. may be used alone or in combination of two or more selected from the group consisting of, through which the amine group may be introduced into the photothermal metal.
  • a compound containing a carboxyl group and a thiol group is preferable, and a mercaptoundecanoic acid, 3-mercaptopropionic acid, 3-mercaptopyruvic acid (3 -mercaptopyruvic acid), 2-mercaptoacetate, cysteine, penicillamine, 4-amino-2-mercaptobutyric acid It can be used alone or in combination of two or more, through which a carboxyl group can be introduced into the photothermal metal.
  • the mixing ratio is not particularly limited in the present invention.
  • the second nanoparticle 3 may include an organic compound 3c.
  • the organic compound 3c prevents the aggregation of photothermal metals in a solvent, increases dispersibility, increases the accessibility of the second nanoparticles to the graphene oxide nanosheets, and plays a role of securing stability in an aqueous solvent.
  • the organic compound 3c may be an organic compound including a functional group having excellent bonding force with the photothermal metal 3a, preferably an organic compound including a thiol group, and specifically, a molecular weight including a thiol group is 500 to 50,000.
  • Phosphorus methoxy polyethylene glycol-thiol mPEG-SH
  • oleyl amine oleylamine
  • polyethylene imine polyethylene imine
  • the organic compound 3c may be added to the photothermal metal 3a in a sufficient amount, and the mixing ratio in manufacturing is not particularly limited in the present invention.
  • the content in the nanocomposite of the support (1), the first nanoparticle (2), and the second nanoparticle (3) including the graphene oxide nanosheets described above is not particularly limited in the present invention, and is separated from the magnetic field.
  • the diameter, volume of the nanocomposite is increased in certain applications, such as using the nanocomposite in a living body
  • the size of the diameter or volume of the nanocomposite according to the present invention is not particularly limited in the present invention, may be designed in consideration of the intended use, the degree of effect required expression.
  • the graphene oxide nanocomposite as described above is a support comprising a single layer of graphene oxide nanosheets;
  • a first nano-containing core layer comprising a magnetic material containing triiron tetraoxide (Fe 3 O 4 ) and a silica shell layer surrounding the core layer and surface-modified with an amine group and covalently included on the graphene oxide nanosheets. particle;
  • photothermal metal particles including gold nanorods having an aspect ratio of 3 to 4 whose surface is modified by a silane group, and are covalently bonded to any one or more of the graphene oxide nanosheets and the first nanoparticles.
  • the second nanoparticles may be included, and thus may express an excellent synergistic effect in the photothermal effect as described below, and may further improve the separation / collection of the graphene oxide nanocomposites.
  • the graphene oxide nanocomposite according to the present invention exhibits excellent photothermal effects due to the synergy between the graphene oxide nanosheets and the second nanoparticles included in the nanocomposite, with a wavelength of 780 nm and a near infrared ray having an intensity of 2 mW / cm 2 .
  • NIR near infrared ray
  • the temperature increased after 100 seconds of laser irradiation is 6 ° C or higher than before laser irradiation
  • the temperature increased after 300 seconds of laser irradiation is 20 ° C or higher than before laser irradiation
  • the laser irradiation 900 After an elapse of time the increased temperature is above 38 ° C compared to before laser irradiation.
  • Figure 11 is a graph showing the temperature increase per hour when the laser irradiation to the nanocomposite according to an embodiment of the present invention, even if only graphene oxide nanosheets are present as the laser irradiation time increases the temperature increases It can be seen that the oxide nanosheets themselves have a photothermal effect.
  • the graphene oxide nanosheets contain the first nanoparticles (first nanoparticles / graphene oxide of Figure 11) compared with the case that contains only the graphene oxide nanosheets, the temperature increase with time is almost the same. It can be seen that the first nanoparticles containing magnetic particles other than the photothermal metal do not affect the photothermal effect.
  • the gold nanorods (second nanoparticles) when irradiating a laser with a large temperature change over time it can be seen that there is a photothermal effect on the gold nanocomposite according to the present invention (first nanoparticles / 2 nanoparticles / graphene oxide) when the laser is irradiated with gold nanorods alone can be seen to be superior in the photothermal effect.
  • the nanocomposite according to the present invention exhibits a synergistic effect that exceeds the sum of the effects of the respective structures, that is, graphene oxide nanosheets and gold nanorods, in light-heating effect, and the synergistic effect is remarkable as the laser irradiation time increases. It can be seen from Figure 11 that the increase.
  • the nanocomposite according to the present invention comprises the steps of (1) preparing a first composite by injecting graphene oxide nanosheets into a solution containing the first nanoparticles having a magnetic; And (2) preparing the second complex by adding the complex to a solution containing the second nanoparticles expressing the photothermal effect.
  • FIG. 12 is a schematic diagram of a manufacturing process according to an embodiment of the present invention.
  • a graphene oxide nanosheet is added to a solution including first nanoparticles having magnetic properties in step (1). It comprises the step of preparing.
  • the first composite may be prepared by mixing 10 to 100 parts by weight of a solution containing the first nanoparticles having magnetic properties with respect to 100 parts by weight of graphene oxide nanosheets and stirring at 20 to 30 ° C. for 10 to 24 hours.
  • the coupling agent, the coupling aid may further comprise 10 to 100 parts by weight based on 100 parts by weight of the graphene oxide nanosheets. If the solution containing the first nanoparticles is included in less than 10 parts by weight, the content of the first nanoparticles bound to the graphene oxide nanosheets is too small to exert the desired magnetism, thus the separation / collection of the nanocomposites is difficult. There may be a problem that may be difficult, and when the amount exceeds 100 parts by weight, the amount of the first nanoparticles that are not bound and increases may be inefficient.
  • the solvent of the solution containing the first nanoparticles may be an organic solvent such as water, ethanol
  • the solvent is a solvent that can disperse the first nanoparticles well without physical and chemical effects on the first nanoparticles
  • the first nanoparticles may be included in the solvent in consideration of the content of the first nanoparticles to be included in the nanocomposite, the content may vary depending on the purpose is not particularly limited in the present invention.
  • the coupling agent may use EDC (1-ethyl-3- (3-dimethylamini-propyl) carbodiimide) and the like when using water as a solvent, NHS (N-hydroxysuccinimide), NHSS (N- hydroxysulfosuccinimide) and the like, but is not limited thereto.
  • the coupling agent serves to form an amide bond (-CONH-) with the carboxyl group and the amine group
  • the coupling aid serves to increase the efficiency when forming the amide bond.
  • the step (1) is an amide between any one or more functional groups selected from the group consisting of a thiol group, an amine group and a carboxyl group contained on the surface of the silica shell layer of the first nanoparticle, and a hydroxyl group and / or carboxyl group included in the graphene oxide nanosheet.
  • Covalent bonds such as bonds may be formed, and thus, the first nanoparticles included in the first complex may express a strong chemical bonding force so that they are not easily separated from the graphene oxide nanosheets.
  • the magnetic first nanoparticle is a core shell structure including a silica shell layer surrounding a magnetic material, and the surface of the silica shell layer may include any one or more functional groups selected from the group consisting of a thiol group, an amine group, and a carboxyl group. have.
  • the graphene oxide nanosheets may be a single layer graphene oxide nanosheets for the expression of excellent effects. Detailed description of the first nanoparticles and the graphene oxide nanosheets, a method of preparing the same, and a description of functional groups capable of covalent bonding are the same as described above, and will be omitted below.
  • step (2) the step of preparing a second complex by adding the first complex to a solution containing the second nanoparticles expressing the photothermal effect.
  • the first complex may be in a dispersed state in an organic solvent, such as ethanol, preferably through step (1), to prepare a second complex by mixing a solution including second nanoparticles in a solution including the first complex. can do.
  • organic solvent such as ethanol
  • the step (2) is preferably 10 to 100 parts by weight of the second nanoparticles with respect to 100 parts by weight of the first complex, if it can be mixed as described above the concentration of the solution containing the first complex, The concentration of the solution containing the second nanoparticles can be changed. If the second nanoparticles are added in less than 10 parts by weight, the content of the second nanoparticles including the photothermal metals contained in the nanocomposite to be manufactured may be insufficient and thus may not be sufficient to express a desired photothermal effect, and 100 parts by weight. When included in excess, the amount of the second nanoparticles that are not bonded to the first composite and the unbound state may increase, resulting in an inefficient process.
  • Step (2) may be prepared a second composite through agitation for 10 to 24 hours at 20 ⁇ 30 °C but is not limited thereto.
  • the second nanoparticles may be photothermal metal nanoparticles surface-modified with one or more functional groups selected from the group consisting of a silane group, an amine group, and a carboxyl group, and the detailed description thereof is the same as described above, and a known conventional technique may be used. As can be, will be omitted below.
  • Step (2) may be any one or more functional groups selected from the group consisting of a silane group, an amine group and a carboxyl group included in the silica shell layer of the first nanoparticles included in the first composite; And a functional group of any one or more of a hydroxyl group and a carboxyl group included in the graphene oxide nanosheets. Strong chemical bonding force to prevent the second nanoparticles from being easily separated from the first complex by forming a covalent bond between any one or more of the functional groups and any one or more functional groups selected from the group consisting of silane groups, amine groups and carboxyl groups on the surface of the photothermal metal nanoparticles Can be expressed.
  • the present invention includes a graphene oxide nanocomposite for cancer cell diagnostics comprising a nanocomposite according to the present invention.
  • the cancer cell diagnostic complex includes a receptor and / or a ligand capable of binding to a target cancer cell, in particular, a metastatic cancer cell present in the blood, in addition to the nanocomposite according to the present invention, after the nanocomposite binds to the desired metastatic cancer cell by magnetic force.
  • Cancer cells can be diagnosed by separating / collecting cancer cells, or by identifying markers such as specific fluorescent substances on nanocomposites to diagnose cancer cells.
  • the diagnosis of cancer cells may be performed by collecting blood, and the presence or absence of cancer cells may be confirmed by forming a magnetic field in the collected blood or developing fluorescent materials through known methods.
  • Receptors and / or ligands that can be included in the cancer cell diagnostic complex according to the present invention can be used ligands or receptors that are commonly used for cancer cell cleaning, the present invention is not particularly limited to this, the receptor and / or ligands in the complex
  • the binding method may be a known conventional method, and the content contained in the composite is not limited in the present invention.
  • the present invention includes a graphene oxide nanocomposite for treating cancer cells comprising a nanocomposite according to the present invention.
  • the therapeutic complex of cancer cells in addition to the nanocomposite according to the present invention, includes a receptor and / or a ligand capable of binding to target cancer cells, in particular, metastatic cancer cells present in the blood, so that the nanocomposite binds to the desired metastatic cancer cells and is then subjected to magnetic force.
  • target cancer cells in particular, metastatic cancer cells present in the blood
  • the nanocomposite binds to the desired metastatic cancer cells and is then subjected to magnetic force.
  • the first nanoparticles included in the nanocomposite according to the present invention include a magnetic nanomaterial, and since the magnetic nanomaterial has a property of generating heat by high frequency, the heating effect is increased when the high frequency is simultaneously applied with a laser. It can maximize the destruction and removal of cancer cells as a substance.
  • the cancer cell treatment complex is harmless to the living body, has no pain, and kills cells indiscriminately without distinguishing cancer cells or normal cells by separating / removing only specific cells, compared to conventional methods of cancer therapy. Can be more efficient than
  • Receptors and / or ligands that may be included in the complex for treating cancer cells according to the present invention may be used ligands or receptors commonly used for cancer cell cleaning, and the present invention is not particularly limited thereto, and the receptor and / or ligand may be complexed.
  • the binding method may be a known conventional method, and the content of the composite is not limited in the present invention.
  • the graphene oxide nanocomposite for diagnosis or treatment of cancer cells according to the present invention may be injected into a blood vessel through an injection at the time of clinical administration, and the injection composition is ethyl oleate in addition to the graphene oxide nanocomposite for diagnosis or treatment of cancer cells according to the present invention.
  • injectable esters such as physiological saline, and the like, and carbohydrates such as glucose, sucrose or dextran, antioxidants such as ascorbic acid or glutathione, chelating to increase stability It may further comprise chelating agents, low molecular weight proteins or other stabilizers.
  • the effective amount of the graphene oxide nanocomposite for diagnosing or treating cancer cells in the injection composition is preferably 1 to 50%, and an injection containing 1 to 100 ml may be administered in the effective amount at the time of diagnosing or treating cancer.
  • injections containing a graphene oxide nanocomposite for cancer cell treatment according to the present invention as an active ingredient may be administered to the subject in a single dose, multiple doses at intervals of 5 to 24 hours in divided doses).
  • the injection dose containing the graphene oxide nanocomposite as an active ingredient for treating cancer cells according to the present invention is determined in consideration of various factors such as age and health condition of the administered subject, an effective dose is determined in this field.
  • One of ordinary skill can determine the appropriate effective dosage.
  • the dialysis of the blood by a conventional method and during dialysis, by continuously forming a magnetic field of 0.1 to 10 Tesla magnetic field strength on the dialysis and cancer cell therapy graphene oxide nanocomposites
  • the combined cancer cells can be cloned and the cancer cells can be destroyed by irradiating the cloned cancer cells with a laser having a wavelength of 700 to 1000 nm to remove metastatic cancer present in the blood.
  • the solids were then separated using a cellulose acetate membrane having a pore diameter of about 450 nm, and the separated solids were purified and washed with distilled water, followed by several drops of 10 wt% aqueous hydrochloric acid solution at 15000 rpm. Centrifugation was carried out for 30 minutes and the final product was vacuum dried for 12 hours to prepare a single layer of graphite oxide nanosheets.
  • TEOS 165 mM tetraethylorthosilicate
  • acetone 5 ml was added to terminate the reaction, and the first nanoparticle was prepared by removing the excess organic solvent by centrifugation at 15,000 rpm for 30 minutes.
  • the first nanoparticles were added to 99.9% by weight of ethanol as a dispersion solvent, and 3-aminopropyltriethoxysilane (APTS, Sigma-Aldrich) was loaded with 100 parts of the first nanoparticles. 10 parts by weight of the parts were added and stirred at room temperature for 6 hours. Thereafter, the prepared nanoparticles were washed in distilled water to prepare surface-modified first nanoparticles.
  • APTS 3-aminopropyltriethoxysilane
  • a gold nanorod growth solution 50 ml of 1 mM of HAuCl 4 ⁇ 4H 2 O (hydrogentetrachloroaurate (III) tetrahydrate) was mixed with 50 ml of 0.2 M CTAB aqueous solution, and then 4 mM ammonium nitrate was dissolved in 1.2 ml of aqueous solution and 7.9 mM ascorbic acid. 0.7 ml of an aqueous bixane solution was mixed by magnetic steering.
  • the prepared seed solution was aged at room temperature for 30 minutes before use, and then 60 ⁇ l of the seed solution was added to 100 ml of the growth solution with stirring. Then, stirring was continued until the color of the solution turned dark red, and then the final product was washed twice with distilled water to remove the CTAB solution after the color was changed to prepare a gold nanorod having an aspect ratio of 4. It was.
  • the prepared gold nanorods were added to about 0.01 g of mPEG-SH (MW 1,000, Laysan Bio) for polyethylene glycolation, and then the polyethylene glycolated gold nanorods were dispersed in 99.9 wt% ethanol.
  • the first nanoparticles of the core shell structure is a structure in which the triiron tetraoxide of Figure 6 (a) is included as a core portion and silica surrounds the core portion.
  • FIG. 9 the composite including the composite of FIG. 8 and the second nanoparticle of FIG. 7 was prepared.
  • UV-Vis absorption spectrum was measured for Preparation Example 1 (a), Comparative Example 1 (b), Preparation Example 3 (c), and Example 1 (d) and shown in FIG. 10. .
  • Example 1 (d) spectrum in FIG. 10, an absorption peak of graphene oxide as Preparation Example 1 (a) at about 250 nm and an absorption peak of second nanoparticles as Preparation Example 3 (c) at about 800 nm are shown. By showing all of the nanocomposite of Example 1 (d) it can be seen that the graphene oxide, including the second nanoparticles.
  • the graphene oxide of Preparation Example 1, the first nanoparticles / graphene oxide composite of Comparative Example 1, the second nanoparticles of Preparation Example 3 and the second nanoparticles / first nano of Example 1 10 parts by weight of the particle / graphene oxide composite was added to 100 parts by weight of distilled water, and then irradiated with a near infrared laser having a wavelength of 780 nm and an intensity of 2 mW / cm 2. At this time, distilled water was used as a control.
  • the second nanoparticles / first nanoparticles / graphene oxide composite according to the present invention have a remarkably excellent light-heating effect compared to the case of the second nanoparticles, and according to the present invention at an increased temperature for each laser irradiation time.
  • the graphene oxide and the second nanoparticles are increased in the photothermal effect through the increase in the temperature of the second nanoparticle / first nanoparticle / graphene oxide composite is greater than the increase temperature and the graphene oxide increase temperature of the second nanoparticle. It can be confirmed that the effect is expressed. This synergistic effect can be confirmed that the longer the laser irradiation time is more remarkable.

Abstract

The present invention relates to a graphene oxide nanocomposite exhibiting an excellent photothermal effect and a manufacturing method therefor, and more specifically, to a graphene oxide nanocomposite exhibiting an excellent photothermal effect and a manufacturing method therefor, wherein the nanocomposite manifests an improved photothermal effect and simultaneously realizes excellent thermal conductivity, thus having an outstanding effect of emitting the heat being generated, and has high light transmittance, thus amplifying the photothermal effect, and the separation of the nanocomposite markedly decreases, and the separation/collection properties of the nanocomposite increase, thus facilitating the reuse of the nanocomposite.

Description

광열효과가 우수한 그래핀 옥사이드 나노복합체 및 그 제조방법Graphene Oxide Nanocomposites with Excellent Photothermal Effects and Manufacturing Method Thereof
본 발명은 광열효과가 우수한 그래핀 옥사이드 나노복합체 및 그 제조방법에 관한 것으로, 보다 상세하게는 나노복합체가 향상된 광열효과를 발현하는 동시에 우수한 열전도도를 구현함에 따라 발생하는 열의 방출효과가 뛰어나고, 높은 광투과도를 가져 광열효과를 증폭시키며, 나노복합체의 분리가 현저히 저하되고, 나노복합체의 분리/수집성이 증가하여 재사용이 용이한 광열효과가 우수한 그래핀 옥사이드 나노복합체 및 그 제조방법에 관한 것이다.The present invention relates to a graphene oxide nanocomposite having excellent light-heating effect and a method of manufacturing the same, and more particularly, the nanocomposite exhibits improved light-heating effect and at the same time has excellent heat conduction effect, and has a high heat release effect. The present invention relates to a graphene oxide nanocomposite having excellent light-heating effect and a method of preparing the same, having a light transmittance, amplifying a light-heating effect, significantly reducing the separation of the nanocomposite, and increasing the separation / collection of the nanocomposite.
그래핀은 과학과 공학적인 부분에서 많은 주목을 받고 있다. 이는 그래핀의 전기적, 광학적, 열적, 기계적 특징과 그와 관련된 탄소 나노 구조체 덕분이다. 이러한 그래핀은 생산에 어려움이 있어 왔지만, 기계적 박리, 산화환원 방법, 에피택시적 성장 및 증기상 증착 등을 통해 합성되고 있다. 이러한 방법들은 그래핀에 기반한 물질의 실현을 나노 기술의 응용을 통해 가능하게 하고 있으며, 이러한 방법 관련하여 대한민국 특허출원 제2010-0117206호 등 그래핀 제조방법이 다양화 되고 있다.Graphene has received a lot of attention in science and engineering. This is due to the electrical, optical, thermal and mechanical properties of graphene and their associated carbon nanostructures. Such graphene has been difficult to produce, but has been synthesized through mechanical exfoliation, redox methods, epitaxy growth, and vapor phase deposition. These methods enable the realization of graphene-based materials through the application of nanotechnology, and graphene manufacturing methods such as Korean Patent Application No. 2010-0117206 have been diversified.
흑연은 상기 그래핀 층들이 z축 방향으로 쌓여있는 층상구조를 가지고 있고 그래파이트 옥사이드 역시 층상구조를 가지고 있다. 하지만 강력한 산화 반응 중 sp2 네트워크가 부분적으로 깨지면서 sp3결합으로 바뀌고 다양한 산소 작용기들이 나노 그래핀의 윗면(basalplane)과 끝(edge) 부분에 공유 결합을 통해 결합된다. 150년이 넘는 역사에도 불구하고 그래파이트 옥사이드의 정확한 화학 구조가 규명되지 못하고 여러 가지 모델들이 제안되어 왔었지만 최근 들어서는 Lerf's model이 일반적으로 받아들여지고 있다. 일반적으로 윗면에는 히드록시기(hydroxyl group)와 에폭시기(epoxy group)가 존재하고 끝부분에는 카르복실기 (carboxyl group)와 케톤기(ketone group)가 존재한다고 알려져 있다.Graphite has a layered structure in which the graphene layers are stacked in the z-axis direction, and graphite oxide also has a layered structure. However, during the strong oxidation reaction, the sp 2 network partially breaks into sp 3 bonds, and various oxygen functional groups are bonded through covalent bonds to the top and edge portions of the nanographene. Despite more than 150 years of history, the exact chemical structure of graphite oxide has not been established and several models have been proposed, but recently Lerf's model is generally accepted. In general, it is known that a hydroxyl group and an epoxy group exist on the top surface and a carboxyl group and a ketone group exist at the end.
상기와 같은 여러 작용기들은 그래핀 옥사이드를 물에 잘 분산시키며 화학적 변형을 가능하게 만들어주는 역할을 한다. 이러한 예로 많은 작용기와 넓은 면적으로 인해 그래핀 옥사이드는 나노 물질의 지지체로 많이 사용되고 있다.The various functional groups as described above serve to disperse the graphene oxide in water and to enable chemical modification. For example, graphene oxide is widely used as a support for nanomaterials due to the large number of functional groups and large areas.
한편, 금속 나노입자란 입자의 크기가 1 내지 1000 nm 에 해당하는 금속 미립자를 의미하며, 전자전이에 필요한 에너지가 물질의 크기에 따라 변화되는 양자크기제한현상(quantum confinement effect) 및 넓은 비표면적으로 인하여 벌크 상태의 물질과는 전혀 다른 광학적, 전기적, 자기적 특성을 나타낸다. 특히, 일부 금속 나노입자는 광열 특성을 나타내는데, 광열효과란 빛을 흡수하여 열을 방출하는 효과를 말한다. 상기 광열효과는 금속 나노입자의 종류, 형상, 크기 등에 따라 달라지고, 금속 나노입자에 조사되는 레이저의 파장 및 세기에 따라서도 달라진다고 알려져 있다. Metal nanoparticles mean metal particles having a particle size of 1 to 1000 nm, and have a large specific surface area and a quantum confinement effect in which the energy required for electron transition is changed according to the size of the material. Because of this, they exhibit completely different optical, electrical and magnetic properties than bulk materials. In particular, some metal nanoparticles exhibit photothermal properties, and the photothermal effect refers to an effect of absorbing light and releasing heat. The photothermal effect is known to vary depending on the type, shape and size of the metal nanoparticles, and also depends on the wavelength and intensity of the laser irradiated to the metal nanoparticles.
최근에는 이러한 광열효과를 이용하여 특정 화학반응의 촉매로 사용되거나 바이러스, 미생물, 암세포 등의 치료제나 환경 오염물질의 제거 등에 응용됨에 따라 광열효과를 가지는 금속 나노입자는 여러 기술분야에 다양하게 활용되고 있다. Recently, as the photothermal effect is used as a catalyst of a specific chemical reaction or applied to the treatment of viruses, microorganisms, cancer cells, etc. or to remove environmental pollutants, metal nanoparticles having a photothermal effect are widely used in various technical fields. have.
그러나 종래에 광열효과를 나타내는 금속 나노입자를 이용하는 경우 목적하는 광열효과를 수득하기 위해서 금속 나노입자를 응집시켜 복합체를 만들었으나 이 경우 조사되는 빛이 복합체 내부까지 투과되기 어려워 금속 나노입자의 함량에 대비해 충분한 광열효과를 수득할 수 없었다.However, in the case of using the metal nanoparticles exhibiting the photothermal effect, in order to obtain a desired photothermal effect, the composite was made by agglomerating the metal nanoparticles, but in this case, the irradiated light is hardly transmitted to the inside of the composite to prepare for the content of the metal nanoparticles. Sufficient photothermal effect could not be obtained.
또한, 응집된 복합체는 개개의 나노입자로 분리되기 쉬워 이를 막기 위해 별도의 물질로 복합체를 캡슐화하는 등 제조공정이 복잡하고 많은 비용이 소요되었으며, 상기 캡슐층은 캡슐 내부에서 발생하는 열을 외부로 전달시키기 보다는 오히려 열의 방출을 막는 부작용이 있었다.In addition, the aggregated complex is easy to be separated into individual nanoparticles, and the manufacturing process is complicated and expensive, such as encapsulating the composite with a separate material in order to prevent this, and the capsule layer is configured to transfer heat generated inside the capsule to the outside. There was a side effect that prevented the release of heat rather than delivering it.
나아가, 광열효과를 발현하는 금속 입자나 이를 응집시킨 복합체 등은 제조시간 길고, 소요비용이 높은데 반하여 사용한 후 이를 다시 분리, 수집하기 어려움에 따라 재사용되지 못하고 버려질 수밖에 없는 문제점이 있었다.Furthermore, the metal particles expressing the photothermal effect or the composites aggregated thereof have a long manufacturing time and high cost, but they cannot be reused and discarded due to difficulty in separating and collecting them after use.
본 발명은 상술한 문제점을 해결하기 위해 안출된 것으로, 본 발명이 해결하고자 하는 첫 번째 과제는 광열효과의 발현을 극대화시키는 동시에 발생하는 열을 외부로 방출되기 용이하며, 높은 광투과도를 가지게 하여 광열효과를 보다 증폭시킬 수 있고, 나노복합체의 분리가 현저히 저하되며, 나노복합체의 분리/수집성이 증가함으로써 재사용이 용이해 제조, 구입비용을 절감할 수 있는 그래핀 옥사이드 나노복합체 및 그 제조방법을 제공하는 것이다.The present invention has been made to solve the above problems, the first problem to be solved by the present invention is to maximize the manifestation of the photothermal effect and at the same time easy to emit the heat generated, and to have a high light transmittance Graphene oxide nanocomposites and methods for producing the same can be further amplified, the separation of nanocomposites is significantly lowered, and the separation / collection of nanocomposites is increased, thereby facilitating reuse and reducing the manufacturing and purchasing costs. To provide.
본 발명이 해결하고자 하는 두 번째 과제는 현저히 우수한 광열효과와 열방출성 및 나노복합체의 분리/수집성을 응용하여 암세포 진단용 및 치료용 나노복합체를 제공하는 것이다.The second problem to be solved by the present invention is to provide a nanocomposite for cancer cell diagnosis and treatment by applying a remarkably excellent photothermal effect, heat release properties and separation / collection of the nanocomposite.
상술한 첫 번째 과제를 해결하기 위해 본 발명은, 그래핀 옥사이드(GO) 나노시트를 포함하는 지지체; 상기 그래핀 옥사이드 나노시트상에 공유결합되어 포함되며, 자성을 띠는 제1 나노입자; 및 상기 그래핀옥사이드(GO) 및 제1 나노입자 중 적어도 하나 이상에 공유결합되어 포함되며, 광열효과를 발현하는 제2 나노입자;를 포함하는 광열효과가 우수한 그래핀 옥사이드 나노복합체를 제공한다.The present invention to solve the first problem described above, the support comprising a graphene oxide (GO) nanosheet; It is included covalently bonded on the graphene oxide nanosheets, the first nanoparticles having a magnetic; And a second nanoparticle covalently bonded to at least one of the graphene oxide (GO) and the first nanoparticle and expressing a photothermal effect. The graphene oxide nanocomposite having excellent photothermal effect is provided.
본 발명의 바람직한 일실시예에 따르면, 상기 나노시트는 단층의 그래핀 옥사이드일 수 있다.According to a preferred embodiment of the present invention, the nanosheet may be a single layer of graphene oxide.
본 발명의 바람직한 또 다른 일실시예에 따르면, 상기 제1 나노입자는 자성물질을 포함하는 코어층; 및 상기 코어층을 둘러싸고, 싸이올기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기를 포함하여 표면 개질된 실리카 쉘층;을 포함할 수 있다.According to another preferred embodiment of the present invention, the first nanoparticles include a core layer comprising a magnetic material; And a surface of the silica shell layer surrounding the core layer and including any one or more functional groups selected from the group consisting of a thiol group, an amine group, and a carboxyl group.
본 발명의 바람직한 다른 일실시예에 따르면, 상기 자성물질은 코발트(Co), 망간(Mn), 철(Fe), 니켈(Ni), 가돌리늄(Gd), 게르마늄(Ge), 알루미늄(Al), 몰리브덴(Mo), MM’2O4및 MxOy로 이루어진 군에서 선택된 어느 하나 이상의 금속물질; 및 코발트-구리(CoCu), 코발트-백금(CoPt), 철-백금(FePt), 코발트-사마륨(CoSm), 니켈-철(NiFe) 및 니켈-철-코발트(NiFeCo)로 이루어진 군에서 선택된 어느 하나 이상의 금속합금;중 어느 하나 이상을 포함할 수 있다.According to another preferred embodiment of the present invention, the magnetic material is cobalt (Co), manganese (Mn), iron (Fe), nickel (Ni), gadolinium (Gd), germanium (Ge), aluminum (Al), Molybdenum (Mo), at least one metal material selected from the group consisting of MM ' 2 O 4 and M x O y ; And cobalt-copper (CoCu), cobalt-platinum (CoPt), iron-platinum (FePt), cobalt-samarium (CoSm), nickel-iron (NiFe), and nickel-iron-cobalt (NiFeCo). One or more metal alloys; may include any one or more.
이때, 상기 M또는 M’은 Co, Mn, Fe, Ni, Gd, Ge, Al, Mo이며, 0<x≤3, 0<y≤5이다.In this case, M or M 'is Co, Mn, Fe, Ni, Gd, Ge, Al, Mo, 0 <x ≤ 3, 0 <y ≤ 5.
본 발명의 바람직한 또 다른 일실시예에 따르면, 상기 제2 나노입자는 실란기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기를 포함하여 표면개질된 광열 금속 나노입자일 수 있다.According to another preferred embodiment of the present invention, the second nanoparticles may be surface-modified photothermal metal nanoparticles including any one or more functional groups selected from the group consisting of a silane group, an amine group and a carboxyl group.
본 발명의 바람직한 다른 일실시예에 따르면, 상기 제2 나노입자 형상은 로드(rod)형일 수 있다.According to another preferred embodiment of the present invention, the second nanoparticle shape may be rod-shaped.
본 발명의 바람직한 또 다른 일실시예에 따르면, 상기 광열 금속 나노입자는 금, 은, 팔라듐, 백금, 구리 및 알루미늄 이루어진 군에서 선택된 어느 하나 이상을 포함할 수 있다.According to another preferred embodiment of the present invention, the photothermal metal nanoparticles may include any one or more selected from the group consisting of gold, silver, palladium, platinum, copper and aluminum.
본 발명의 바람직한 다른 일실시예에 따르면, 상기 나노복합체는 단층의 그래핀 옥사이드 나노시트를 포함하는 지지체; 사산화삼철(Fe3O4)을 포함하는 자성물질을 포함하는 코어층 및 상기 코어층을 둘러싸고 아민기로 표면개질된 실리카 쉘층을 포함하고 상기 그래핀 옥사이드 나노시트상에 공유결합하여 포함되는 제1 나노입자; 및 표면이 실란기로 개질된 종횡비(aspect ratio)가 3 ~ 4인 금나노로드를 포함하는 광열금속입자를 포함하고, 상기 그래핀 옥사이드 나노시트 및 제1 나노입자 중 어느 하나 이상과 공유결합하여 포함되는 제2 나노입자;를 포함할 수 있다.According to another preferred embodiment of the present invention, the nanocomposite includes a support including a single layer of graphene oxide nanosheets; A first nano-containing core layer comprising a magnetic material containing triiron tetraoxide (Fe 3 O 4 ) and a silica shell layer surrounding the core layer and surface-modified with an amine group and covalently included on the graphene oxide nanosheets. particle; And photothermal metal particles including gold nanorods having an aspect ratio of 3 to 4 whose surface is modified by a silane group, and are covalently bonded to any one or more of the graphene oxide nanosheets and the first nanoparticles. It may include a second nanoparticle.
본 발명의 바람직한 또 다른 실시예에 따르면, 상기 나노복합체는 파장이 780nm이고, 세기가 2mW/cm2인 레이저를 조사시 하기의 조건 (1) 내지 (3)을 만족할 수 있다.According to another preferred embodiment of the present invention, the nanocomposite may satisfy the following conditions (1) to (3) when irradiating a laser having a wavelength of 780 nm and an intensity of 2 mW / cm 2 .
(1) 레이저 조사 100초 경과 후 증가된 온도가 레이저 조사 전에 비해 6℃ 이상이고, (2) 레이저 조사 300초 경과 후 증가된 온도가 레이저 조사 전에 비해 20℃ 이상이며, (3) 레이져 조사 900 초 경과 후 증가된 온도가 레이저 조사 전에 비해 38℃ 이상임.(1) The temperature increased after 100 seconds of laser irradiation is 6 ° C or higher than before laser irradiation, (2) The temperature increased after 300 seconds of laser irradiation is 20 ° C or higher than before laser irradiation, and (3) The laser irradiation 900 After an elapse of time the increased temperature is above 38 ° C compared to before laser irradiation.
또한, 상술한 첫 번째 과제를 해결하기 위해 본 발명은, (1) 자성을 띠는 제1 나노입자를 포함하는 용액에 그래핀 옥사이드 나노시트를 투입하여 제1 복합체를 제조하는 단계; 및 (2) 상기 제1 복합체를 광열효과를 발현하는 제2 나노입자가 포함된 용액에 투입하여 제2 복합체를 제조하는 단계;를 포함하는 광열효과가 우수한 그래핀 옥사이드 나노복합체 제조방법을 제공한다.In addition, in order to solve the first problem described above, the present invention, (1) preparing a first composite by injecting graphene oxide nanosheets into a solution containing the first nanoparticles having a magnetic; And (2) preparing a second complex by adding the first complex to a solution containing second nanoparticles expressing a photothermal effect, thereby providing a graphene oxide nanocomposite having excellent photothermal effects. .
본 발명의 바람직한 일실시예에 따르면, 상기 (1) 단계는 제1 나노입자의 실리카 쉘층 표면에 포함된 싸이올기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기와 그래핀 옥사이드 나노시트에 포함된 싸이올기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기 간에 공유결합을 형성시킬 수 있다.According to a preferred embodiment of the present invention, the step (1) is one or more functional groups selected from the group consisting of a thiol group, an amine group and a carboxyl group contained on the surface of the silica shell layer of the first nanoparticles on the graphene oxide nanosheets Covalent bonds may be formed between any one or more functional groups selected from the group consisting of thiol groups, amine groups and carboxyl groups.
본 발명의 바람직한 다른 일실시예에 따르면, 상기 (2) 단계는 제1 복합체에 포함된 제1 나노입자의 실리카 쉘층에 포함된 싸이올기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기; 및 그래핀 옥사이드 나노시트에 포함된 싸이올기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기; 중 어느 하나 이상의 작용기와 광열 금속 나노입자 표면의 실란기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기 간에 공유결합을 형성시킬 수 있다.According to another preferred embodiment of the present invention, step (2) comprises at least one functional group selected from the group consisting of a thiol group, an amine group and a carboxyl group included in the silica shell layer of the first nanoparticles included in the first composite; And one or more functional groups selected from the group consisting of a thiol group, an amine group, and a carboxyl group included in the graphene oxide nanosheets; Covalent bonds may be formed between any one or more of the functional groups and any one or more functional groups selected from the group consisting of silane groups, amine groups and carboxyl groups on the surface of the photothermal metal nanoparticles.
한편, 상술한 두 번째 과제를 해결하기 위해 본 발명은, 본 발명에 따른 나노복합체를 포함하는 암세포 진단용 그래핀 옥사이드 나노복합체를 제공한다.On the other hand, the present invention to solve the above-described second problem, provides a graphene oxide nanocomposite for cancer cell diagnostics comprising a nanocomposite according to the present invention.
또한, 상술한 두 번째 과제를 해결하기 위해 본 발명은, 본 발명에 따른 나노복합체를 포함하는 암세포 치료용 그래핀 옥사이드 나노복합체를 제공한다.The present invention also provides a graphene oxide nanocomposite for treating cancer cells, including the nanocomposite according to the present invention.
이하, 본 발명에서 사용된 용어에 대해 설명한다.Hereinafter, terms used in the present invention will be described.
본 발명에서 사용되는 “그래핀 옥사이드 나노시트”란 그래파이트를 물리적, 화학적인 방법으로 박리화 시킨 나노단위의 두께를 가지는 판상의 그래핀 옥사이드를 의미한다.As used herein, the term “graphene oxide nanosheets” refers to a graphene oxide having a thickness of nano units obtained by exfoliating graphite by physical and chemical methods.
본 발명에서 사용되는 “광열 금속 나노입자” 란 광열 특성, 즉 광 흡수에 따라 열을 발생하는 특성을 지닌 금속 나노입자를 의미한다.As used herein, the term “photothermal metal nanoparticles” refers to metal nanoparticles having photothermal characteristics, that is, heat generation depending on light absorption.
본 발명의 나노복합체는 향상된 광열효과를 발현하는 동시에 우수한 열전도도를 구현함에 따라 발생하는 열의 방출효과가 뛰어나고, 높은 광투과도를 가져 광열효과를 보다 더 증폭시킬 수 있으며, 나노복합체의 분리가 현저히 저하됨에 따라 내구성이 우수하고, 나노복합체의 분리/수집성이 증가하여 재사용이 용이함에 따라 제조/구입비용을 절감할 수 있고 자원재활용에 따라 환경오염 방지 측면에서 유익하다.The nanocomposite of the present invention exhibits an improved photothermal effect and at the same time has excellent thermal conductivity, has an excellent effect of releasing heat, and has a high light transmittance, thereby further amplifying the photothermal effect, and the separation of the nanocomposite is significantly reduced. As a result, the durability is excellent, and the separation / collection of the nanocomposites is increased, and thus the reuse is easy, thereby reducing the manufacturing / purchasing cost and it is beneficial in terms of preventing environmental pollution according to resource recycling.
도 1은 본 발명의 바람직한 일실시예에 따른 나노복합체의 모식도이다.1 is a schematic diagram of a nanocomposite according to an embodiment of the present invention.
도 2는 본 발명의 바람직한 일실시예에 따른 제1 나노입자의 단면 모식도이다.Figure 2 is a schematic cross-sectional view of the first nanoparticles according to an embodiment of the present invention.
도 3은 본 발명의 바람직한 일실시예에 따른 그래핀 옥사이드 나노시트상에 공유결합된 제1 나노입자의 모식도이다.Figure 3 is a schematic diagram of the first nanoparticles covalently bonded on the graphene oxide nanosheets according to an embodiment of the present invention.
도 4는 본 발명의 바람직한 일실시예에 따른 제2 나노입자의 모식도이다.Figure 4 is a schematic diagram of the second nanoparticles according to an embodiment of the present invention.
도 5는 본 발명의 바람직한 일실시예에 포함되는 그래핀 옥사이드의 주사전자현미경(TEM) 사진이다.5 is a scanning electron microscope (TEM) photograph of graphene oxide included in one preferred embodiment of the present invention.
도 6은 본 발명의 바람직한 일실시예에 포함되는 사산화삼철(a) 및 이를 포함하는 제1 나노입자(b)의 주사전자현미경(TEM) 사진이다.6 is a scanning electron microscope (TEM) photograph of triiron tetraoxide (a) and the first nanoparticle (b) including the same, included in a preferred embodiment of the present invention.
도 7은 본 발명의 바람직한 일실시예에 포함되는 금 나노로드를 포함하는 제2 나노입자의 주사전자현미경(TEM) 사진이다.7 is a scanning electron microscope (TEM) photograph of the second nanoparticles including the gold nanorods included in the preferred embodiment of the present invention.
도 8은 본 발명의 비교예에 따른 그래핀옥사이드와 제1 나노입자만을 포함하는 복합체의 주사전자현미경(TEM) 사진이다.8 is a scanning electron microscope (TEM) photograph of a composite including only graphene oxide and first nanoparticles according to a comparative example of the present invention.
도 9는 본 발명의 바람직한 일실시예에 따른 그래핀옥사이드 나노복합체의 주사전자현미경(TEM) 사진이다.9 is a scanning electron microscope (TEM) photograph of the graphene oxide nanocomposite according to an embodiment of the present invention.
도 10은 자외선-가시광선 흡광도 스펙트럼을 나타낸다.10 shows ultraviolet-visible absorbance spectrum.
도 11은 파장이 780nm, 세기가 2mW/㎠인 근적외선 레이저 조사시 시간당 온도를 나타낸 그래프이다.FIG. 11 is a graph showing the temperature per hour when irradiating near infrared laser having a wavelength of 780 nm and an intensity of 2 mW / cm 2.
도 12는 본 발명의 바람직한 일실시예에 따른 그래핀 옥사이드 나노복합체의 제조공정을 나타낸 모식도이다.12 is a schematic diagram showing a manufacturing process of graphene oxide nanocomposite according to an embodiment of the present invention.
이하, 본 발명을 보다 상세하게 설명한다.Hereinafter, the present invention will be described in more detail.
상술한 바와 같이 종래에 광열효과를 나타내는 금속 나노입자이 복합체는 목적하는 광열효과를 수득하기 위해서 금속 나노입자를 응집시켜 복합체를 만들었으나 이 경우 조사되는 빛이 복합체 내부까지 투과되기 어려워 충분한 광열효과를 수득할 수 없었고, 응집된 복합체는 개개의 나노입자로 분리되기 쉬운 문제점이 있었으며, 이를 방지하기 위한 보호막은 제조공정의 복잡화, 많은 비용의 소요 및 열의 방출을 막는 문제점이 있었다. 또한, 복합체를 한번 사용한 후 이를 다시 분리, 수집하기 어려워 재사용되지 못하고 일회성으로 사용되는 문제점이 있었다.As described above, the composite of the metal nanoparticles exhibiting the photothermal effect is formed by agglomeration of the metal nanoparticles to obtain the desired photothermal effect, but in this case, the irradiated light is hardly transmitted to the inside of the composite to obtain sufficient photothermal effect. The agglomerated composites could not be easily separated into individual nanoparticles, and a protective film for preventing them had a problem of complicated manufacturing process, high cost, and heat emission. In addition, once the complex is used, it is difficult to separate and collect it again, so that it cannot be reused and has been used as a one-time problem.
이에 본 발명에서는 그래핀 옥사이드(GO) 나노시트를 포함하는 지지체; 상기 그래핀 옥사이드 나노시트에 공유결합되어 포함되며, 자성을 띠는 제1 나노입자; 및 상기 그래핀옥사이드(GO) 및 제1 나노입자 중 적어도 하나 이상에 공유결합되어 포함되며, 광열효과를 발현하는 제2 나노입자;를 포함하는 광열효과가 우수한 그래핀 옥사이드 나노복합체를 제공함으로써 상술한 문제의 해결을 모색하였다. 이를 통해 향상된 광열효과를 발현하는 동시에 우수한 열전도도를 구현함에 따라 발생하는 열의 방출효과가 뛰어나고, 높은 광투과도를 가져 광열효과를 보다 더 증폭시킬 수 있고, 나노복합체의 분리가 현저히 저하됨에 따라 내구성이 우수하며, 나노복합체의 분리/수집성이 증가하여 재사용이 용이함에 따라 제조/구입비용을 절감할 수 있고 자원재활용에 따라 환경오염 방지 측면에서 기여할 수 있다. In the present invention, a support comprising a graphene oxide (GO) nanosheets; Covalently bonded to the graphene oxide nanosheets and include magnetic first nanoparticles; And a second nanoparticle covalently bonded to at least one or more of the graphene oxide (GO) and the first nanoparticle, and expressing a photothermal effect. I sought to solve a problem. This results in an improved photothermal effect and excellent heat conduction effect, and excellent light emission effect, high light transmittance, which can further amplify the photothermal effect, and the durability of the nanocomposite is significantly reduced. It is excellent and can increase the separation / collection of the nanocomposite to facilitate the reuse, can reduce the manufacturing / purchase cost and contribute to the prevention of environmental pollution according to the resource recycling.
구체적으로 도 1은 본 발명의 바람직한 일실시예에 따른 나노복합체의 모식도로써, 그래핀 옥사이드 나노복합체는 그래핀 옥사이드(GO) 나노시트를 포함하는 지지체(1)상에 공유결합된 자성을 띠는 제1 나노입자(2)와 그래핀 옥사이드 나노시트(1) 및/또는 제1 나노입자(2)와 공유결합된 광열효과를 발현하는 제2 나노입자(3)를 포함할 수 있다. Specifically, Figure 1 is a schematic diagram of a nanocomposite according to an embodiment of the present invention, the graphene oxide nanocomposite is magnetically covalently bonded on the support (1) comprising a graphene oxide (GO) nanosheet The first nanoparticle 2 and the graphene oxide nanosheet 1 and / or the second nanoparticle 3 expressing a photothermal effect covalently bonded with the first nanoparticle 2 may be included.
먼저, 그래핀 옥사이드(GO) 나노시트를 포함하는 지지체(1)에 대해 설명한다.First, the support 1 including the graphene oxide (GO) nanosheets will be described.
그래핀 옥사이드 나노시트는 하기에 설명할 제1 나노입자(2) 및 제2 나노입자(3)와 화학적 결합이 가능한 지지체 기능을 담당하는 동시에 제2 나노입자에서 발생하는 열을 전달 및 외부로 방출시키며, 광열효과를 증폭시키는 효과를 발현할 수 있다. The graphene oxide nanosheets serve as a supporter capable of chemically bonding with the first nanoparticles 2 and the second nanoparticles 3, which will be described below, while simultaneously transferring and dissipating heat generated from the second nanoparticles to the outside. And it can express the effect of amplifying the photothermal effect.
구체적으로, 그래핀 옥사이드는 히드록시기(hydroxyl group), 에폭시기(epoxy group), 카르복실기 (carboxyl group) 및 케톤기(ketone group)기와 같은 작용기를 표면이나 끝부분에 포함하고 있으며, 이러한 작용기는 후술할 제1 나노입자(2)와 제2 나노입자(3)를 그래핀 옥사이드 나노시트에 화학적으로 결합시킬 수 있는 링커역할을 할 수 있다. 또한, 그래핀 옥사이드는 최대 5,000W/mK에 달하는 높은 열전도도를 가지고 있어 발생하는 열을 전달 및 외부로 방출시키는데 있어 다른 소재의 지지체에 비해 매우 유리하다. 나아가, 그래핀 옥사이드 자체도 일정 수준의 광열효과가 있으며, 최대 97.7%에 달하는 광투과도를 발현함에 따라 레이저 등의 빛을 조사시에 반사율이 낮아 나노복합체의 광열효과를 보다 더 증폭시킬 수 있는 이점이 있다. Specifically, graphene oxide includes a functional group such as a hydroxyl group, an epoxy group, an carboxyl group, and a ketone group at the surface or the end thereof, and the functional group may be described later. The first nanoparticles (2) and the second nanoparticles (3) may act as a linker capable of chemically bonding to the graphene oxide nanosheets. In addition, graphene oxide has a high thermal conductivity of up to 5,000 W / mK is very advantageous compared to the support of other materials in the transfer and release of heat generated. Furthermore, graphene oxide itself has a certain level of photothermal effect, and as a result of expressing light transmittance of up to 97.7%, the reflectance is low when irradiating light such as a laser to further amplify the photothermal effect of the nanocomposite. There is this.
한편, 본 발명의 목적을 달성하기 위해 환원된 그래핀 옥사이드(RGO) 나노시트는 바람직하지 않을 수 있다. 환원된 그래핀 옥사이드 나노시트의 경우 상술한 것과 같은 각종 작용기가 환원됨에 따라 제1 나노입자(2) 및/또는 제2 나노입자(3)와 화학적으로 결합시킬 수 있는 작용기의 부재로 인해 보다 더 강력한 지지체와 나노입자의 결합을 어렵게 하는 문제점이 있을 수 있다. On the other hand, reduced graphene oxide (RGO) nanosheets may be undesirable to achieve the object of the present invention. In the case of the reduced graphene oxide nanosheets, various functional groups such as those described above are reduced, further due to the absence of functional groups capable of chemically bonding with the first nanoparticles 2 and / or the second nanoparticles 3. There may be a problem that makes the bonding of the strong support and the nanoparticles difficult.
본 발명의 바람직한 일실시예에 따르면, 상기 나노시트는 바람직하게는 단층의 그래핀 옥사이드일 수 있는데, 이는 발생하는 열의 전달에 있어 다층인 경우에 비해 유리하기 때문이다. 구체적으로 다층의 그래핀 옥사이드는 층간에 공기를 포함하고 있어 열전도도를 저하시킬 수 있으므로 열의 전달이나 방출효율을 높이기 위해 단층의 그래핀 옥사이드 나노시트를 사용함이 바람직하다. 이러한 단층의 그래핀 옥사이드 나노시트의 두께는 약 0.5 ~ 3nm일 수 있으며, 바람직하게는 0.8 ~ 1.5nm일 수 있다. According to a preferred embodiment of the present invention, the nanosheet may preferably be a single layer of graphene oxide, because it is advantageous in the transfer of heat generated as compared to the multilayer case. Specifically, since the graphene oxide of the multi layer includes air between layers, the thermal conductivity may be reduced, and thus, it is preferable to use a single layer of graphene oxide nanosheets to increase heat transfer or release efficiency. The thickness of the graphene oxide nanosheets of such a single layer may be about 0.5 to 3nm, preferably 0.8 to 1.5nm.
본 발명에 따른 나노복합체에 포함될 수 있는 그래핀 옥사이드 나노시트의 면적은 하기에 설명할 제1 나노입자(2) 및 제2 나노입자(3)를 충분히 나노시트 상에 포함시킬 수 있을 정도의 면적이라면 특별히 한정하지 않으며, 바람직하게는 0.1 ~ 1 ㎛2일수있다. The area of the graphene oxide nanosheets that may be included in the nanocomposite according to the present invention is an area sufficient to include the first nanoparticles 2 and the second nanoparticles 3, which will be described below, on the nanosheets. If it is, it does not specifically limit, Preferably it may be 0.1-1 micrometer <2> .
한편, 본 발명에 포함되는 그래핀 옥사이드(GO) 나노시트는 통상적인 공지관용의 방법에 의해 제조되는 그래핀 옥사이드(GO)일 수 있으며, 이에 본 발명에서는 그래핀 옥사이드(GO)의 제조방법에 대해 특별히 한정하지 않는다. 다만 바람직하게는 공지의 변형 훔머법(modified Hummers method)에 따라 그래파이트 플래이크로부터 그래핀 옥사이드 나노시트를 제조할 수 있으며, 제조된 그래핀 옥사이드 나노시트에 대해 초음파 조사 등을 통해 박리 공정을 실시함으로써 제조될 수 있다.Meanwhile, the graphene oxide (GO) nanosheets included in the present invention may be graphene oxide (GO) prepared by a conventional publicly known method, and thus, in the present invention, a method for preparing graphene oxide (GO) It does not specifically limit about. However, preferably, the graphene oxide nanosheets may be manufactured from graphite plaques according to a known modified Hummers method, and the exfoliation process may be performed through ultrasonic irradiation on the prepared graphene oxide nanosheets. Can be prepared.
그래핀 옥사이드(GO) 나노시트의 제조방법을 보다 구체적으로 살펴보면, 그래파이트 플래이크 100 중량부에 대해 5,000 ~ 20,000 중량부의 90% 이상의 황산수용액 및 85% 이상의 인산수용액 혼합용액(혼합비율이 농축황산과 인산수용액이 8 ~ 9.5 : 1 부피비)을 혼합한 후, 30 ~ 40℃에서 2 ~ 3시간 천천히 교반하면서 과망간산칼륨을 그래파이트 플래이크 100 중량부에 대해 400 ~ 600 중량부 투입할 수 있다. 이후 혼합용액을 3 ~ 4℃로 냉각시킨 후 30중량% 과산화수소 수용액이 0.5 ~ 2ml 첨가된 증류수 300 ~ 500mL를 투입하여 6 ~ 7℃에서 200~ 500rpm으로 교반하면서 과량의 과망간산칼륨 제거과정을 거칠 수 있다. 고형물의 분리를 위해 이후 기공공경이 약 300 ~ 600nm인 셀룰로오스 아세테이트 막을 사용하여 제조된 용액을 필터링할 수 있으며, 걸러진 고형물질을 더 정제, 세척한 후 10 ~ 12중량% 염산수용액을 몇 방울 떨어뜨려 원심분리하고 최종 제조물을 진공건조 시켜 그래파이트 옥사이드 나노시트를 제조할 수 있다. 이러한 구체적인 제조방법은 본 발명에 포함되는 그래핀 옥사이드 나노시트의 일제조예이며, 이에 한정되는 것은 아니다. 구체적으로 도 5는 상기의 제조방법으로 제조된 그래핀 옥사이드 나노시트의 주사전자현미경 사진을 나타낸다.Looking at the production method of the graphene oxide (GO) nanosheets in more detail, 5,000 ~ 20,000 parts by weight of 90% or more sulfuric acid solution and 85% or more aqueous solution of phosphoric acid solution (mixed ratio of concentrated sulfuric acid and After mixing the aqueous solution of phosphate 8 ~ 9.5: 1 by volume), 400 to 600 parts by weight of potassium permanganate can be added to 100 parts by weight of graphite plaque while slowly stirring for 2 to 3 hours at 30 to 40 ℃. After cooling the mixed solution to 3 ~ 4 ℃ and added 300 ~ 500mL of 30% by weight aqueous hydrogen peroxide solution 0.5 ~ 2ml of distilled water and stirred at 200 ~ 500rpm at 6 ~ 7 ℃ to remove excess potassium permanganate have. For the separation of solids, the prepared solution can be filtered using a cellulose acetate membrane having a pore diameter of about 300 to 600 nm, and the filtered solid material is further purified and washed, and then a few drops of 10-12 wt% aqueous hydrochloric acid solution is added. Graphite oxide nanosheets can be prepared by centrifugation and vacuum drying the final product. This specific manufacturing method is one example of manufacturing the graphene oxide nanosheets included in the present invention, but is not limited thereto. Specifically, Figure 5 shows a scanning electron micrograph of the graphene oxide nanosheets prepared by the above method.
다음으로 지지체(1)에 포함된 그래핀 옥사이드 나노시트상에 공유결합되며, 자성을 띠는 제1 나노입자(2)에 대해 설명한다.Next, the first nanoparticle 2 covalently bonded on the graphene oxide nanosheets included in the support 1 and having magnetic properties will be described.
종래의 광열효과를 이용하는 복합체들은 제조과정이 복잡하고, 광열효과를 발현하고, 효과가 뛰어난 금속이 대체로 금, 은, 백금 등의 유가금속인 바 제조비용이 높은데 반하여 크기가 나노사이즈로 매우 작아 한번 사용 후 이를 분리, 수집하기 어렵고, 높은 제조비용 및/또는 구입비용을 다시 소비해야 되는 문제점이 있었다. Conventional composites using photothermal effect are complicated manufacturing process, express photothermal effect, and excellent metals are valuable metals such as gold, silver, platinum, etc. It is difficult to separate and collect it after use, and there is a problem in that a high manufacturing cost and / or purchase cost must be consumed again.
그러나 본 발명에 따른 제1 나노입자(2)는 자성을 가지는 입자를 포함함으로써, 나노복합체의 사용 후에도 자기장을 이용하여 쉽게 분리, 수집될 수 있어 나노복합체의 재활용 및 비용절감 측면에서 매우 유리하다. However, since the first nanoparticles 2 according to the present invention include particles having magnetic properties, they can be easily separated and collected by using a magnetic field even after using the nanocomposites, which is very advantageous in terms of recycling and cost reduction of the nanocomposites.
본 발명의 바람직한 일실시예에 따르면, 제1 나노입자(2)는 자성물질을 포함하는 코어층; 및 상기 코어층을 둘러싸고, 실란기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기를 포함하여 표면 개질된 실리카 쉘층;을 포함할 수 있다. 구체적으로 도 2는 본 발명의 바람직한 일실시예에 따른 제1 나노입자(2)의 단면 모식도로써, 제1 나노입자(2)는 자성물질을 포함하는 코어층(2a)을 둘러싸고 있는 실리카 쉘층(2b)을 포함하는 코어쉘 구조로써, 실리카 쉘층(2b)의 표면이 개질됨에 따라 아민기(2c)를 포함할 수 있다. 이러한 제1 나노입자(2)의 직경은 본 발명에서 특별히 한정하지 않으나, 아민기(2c)를 제외하고 1 ~ 100nm일 수 있고, 바람직하게는 1 ~ 20 nm일 수 있다. 자성 나노입자는 표면개질의 용이성 측면에서 실리카를 쉘층으로 포함할 수 있으나, 이에 한정되는 것은 아니며, 은, 금, 백금 등의 금속 또는 산화아연(ZnO), 산화알루미늄(Al2O3)및 이산화티탄 등의 산화물 등으로 이루어진 쉘층을 포함할 수 있다.According to one preferred embodiment of the present invention, the first nanoparticles 2 includes a core layer including a magnetic material; And a surface of the silica shell layer surrounding the core layer and including any one or more functional groups selected from the group consisting of a silane group, an amine group, and a carboxyl group. Specifically, FIG. 2 is a schematic cross-sectional view of the first nanoparticles 2 according to an exemplary embodiment of the present invention, in which the first nanoparticles 2 have a silica shell layer surrounding the core layer 2a containing a magnetic material ( As a core shell structure including 2b), an amine group 2c may be included as the surface of the silica shell layer 2b is modified. The diameter of the first nanoparticles 2 is not particularly limited in the present invention, but may be 1 to 100 nm, preferably 1 to 20 nm, except for the amine group 2c. Magnetic nanoparticles may include silica as a shell layer in terms of ease of surface modification, but are not limited thereto, and metals such as silver, gold, and platinum or zinc oxide (ZnO), aluminum oxide (Al 2 O 3 ), and dioxide The shell layer which consists of oxides, such as titanium, can be included.
먼저, 상기 자성물질을 포함하는 코어층(2a)은 나노입자로 제조될 수 있고, 자성을 띠는 물질인 경우 제한 없이 포함할 수 있다. 바람직하게는 상기 자성 물질은 코발트(Co), 망간(Mn), 철(Fe), 니켈(Ni), 가돌리늄(Gd), 게르마늄(Ge), 알루미늄(Al), 몰리브덴(Mo), MM’2O4및 MxOy로 이루어진 군에서 선택된 어느 하나 이상의 금속물질을 사용할 수 있다. 이때, 상기 M 또는 M’은 Co, Mn, Fe, Ni, Gd, Ge, Al, Mo이다. 또한 상기 자성물질은 코발트-구리(CoCu), 코발트-백금(CoPt), 철-백금(FePt), 코발트-사마륨(CoSm), 니켈-철(NiFe) 및 니켈-철-코발트(NiFeCo)로 이루어진 군에서 선택된 어느 하나 이상의 자성합금을 사용할 수 있고, 또는 상술한 금속물질, 자성합금들을 2종 이상 병용하여 사용할 수도 있다. First, the core layer 2a including the magnetic material may be made of nanoparticles, and may include any magnetic material without limitation. Preferably, the magnetic material is cobalt (Co), manganese (Mn), iron (Fe), nickel (Ni), gadolinium (Gd), germanium (Ge), aluminum (Al), molybdenum (Mo), MM ' 2 Any one or more metal materials selected from the group consisting of O 4 and M x O y may be used. In this case, M or M 'is Co, Mn, Fe, Ni, Gd, Ge, Al, Mo. In addition, the magnetic material is made of cobalt-copper (CoCu), cobalt-platinum (CoPt), iron-platinum (FePt), cobalt-samarium (CoSm), nickel-iron (NiFe) and nickel-iron-cobalt (NiFeCo) Any one or more magnetic alloys selected from the group may be used, or two or more of the above-described metal materials and magnetic alloys may be used in combination.
상기 자성물질의 구체적인 형상은 특별히 한정하는 것은 아니며, 구, 막대, 성상형 등 일 수 있다. 또한, 상기 자성물질은 1개의 입자 및/또는 여러 입자가 응집된 형태일 수도 있다. 상기 자성물질의 직경은 특별히 한정되는 것은 아니나 제조의 용이성, 목적하는 물성발현 등을 고려하여 바람직하게는 1 ~ 100nm일 수 있다. 상기 직경의 경우 자성물질의 형상이 구형이 아닌 경우 자성물질 외표면의 한 점에서 외표면의 다른 한 점까지의 거리 중 최대 거리를 의미한다.The specific shape of the magnetic material is not particularly limited, and may be a sphere, a rod, a star shape, or the like. In addition, the magnetic material may be in a form in which one particle and / or several particles are aggregated. The diameter of the magnetic material is not particularly limited, but may be preferably 1 to 100 nm in consideration of ease of manufacture, expression of desired physical properties, and the like. In the case of the diameter, when the shape of the magnetic material is not spherical, it means the maximum distance from one point of the outer surface of the magnetic material to the other point of the outer surface.
다음으로, 상기 자성물질을 포함하는 코어층(2a)을 둘러싸는 실리카 쉘층(2b)에 대해 설명한다. Next, the silica shell layer 2b surrounding the core layer 2a containing the magnetic material will be described.
상술한 자성물질을 포함하는 코어층(2a)들은 물에 분산이 어렵고 표면을 개질시키는 것이 용이하지 않아 본 발명에 포함되는 지지체(1)에 쉽게 결합시킬 수 없는 문제점이 있다. 이에 따라 자성물질을 포함하는 코어층(2a)을 실리카로 코팅하여 쉘층으로 포함시킴으로써 물에 분산이 잘되게 하고, 표면개질을 용이하게 함으로써, 제1 나노입자를 그래핀 옥사이드 나노시트 주변으로 유도하여 그래핀 옥사이드 나노시트상에 존재하는 작용기와 제1 나노입자 표면의 작용기 간에 결합이 발생할 확률을 높이는 이점이 있다.The core layer 2a including the magnetic material described above has a problem that it is difficult to disperse in water and not easy to modify the surface, so that the core layer 2a cannot be easily bonded to the support 1 included in the present invention. Accordingly, the core layer 2a containing the magnetic material is coated with silica to be included as a shell layer so as to be dispersed in water well and to facilitate surface modification, thereby inducing the first nanoparticles around the graphene oxide nanosheets. There is an advantage of increasing the probability of the bonding between the functional groups present on the pin oxide nanosheets and the functional groups on the surface of the first nanoparticles.
상기 실리카 쉘층(2b)의 두께는 충분한 수분산성을 발현할 수 있을 정도이면 특별히 한정되지 않으나, 바람직하게는 1 ~ 50nm 두께로 형성될 수 있으며, 실리카 쉘층(2b)을 형성시키는 구체적인 방법은 본 발명에서는 특별히 한정하지 않으며, 공지관용의 기술을 사용할 수 있고, 바람직하게는 마이크로에멀젼법에 의해 실리카 쉘층을 형성시킬 수 있다. The thickness of the silica shell layer 2b is not particularly limited as long as it can express sufficient water dispersibility. Preferably, the thickness of the silica shell layer 2b may be formed to a thickness of 1 to 50 nm, and a specific method of forming the silica shell layer 2b may include the present invention. In particular, a well-known technique can be used, Preferably, a silica shell layer can be formed by a microemulsion method.
구체적으로 자성물질 나노입자를 사이클로헥산, 헵탄, 옥탄, 데칸 등의 분산용매에 분산시킨 후 20 ~ 40중량%의 암모니아수를 투입하고, 옥탄올, Triton-X100등의 유기용매, 실리카전구체를 투입하여 실리카 쉘층을 형성시킬 수 있다. 더 구체적으로 상기 자성물질 나노입자, 분산용매 및 암모니아수는 1 : 200 ~ 400 : 0.1 ~ 0.3 부피비로 혼합할 수 있고, 자성물질 나노입자 100 중량부에 대해 상기 유기용매를 10 ~ 100 중량부, 실리카 전구체를 0.01 ~ 1 중량부로 혼합하여 실리카 쉘층을 제조할 수 있다. 상기 실리카 전구체의 구체적인 예로는 테트라메틸오르소실리케이트, 테트라에틸오르소실리케이트, 테트라부틸오르소실리케이트, 소디움실리케이트, 소디움메타실리케이트 등을 단독 또는 2종 이상 혼합하여 사용할 수 있다. 다만 상기 방법은 일예시이며, 이러한 제조방법에 제한되는 것은 아니다. Specifically, after dispersing the magnetic nanoparticles in a dispersion solvent such as cyclohexane, heptane, octane, and decane, 20 to 40% by weight of ammonia is added thereto, and an organic solvent such as octanol and Triton-X100 and a silica precursor are added thereto. The silica shell layer can be formed. More specifically, the magnetic material nanoparticles, the dispersion solvent and ammonia water may be mixed in a volume ratio of 1: 200 to 400: 0.1 to 0.3, and the organic solvent is 10 to 100 parts by weight based on 100 parts by weight of the magnetic material nanoparticles, and silica. The silica shell layer may be prepared by mixing the precursor at 0.01 to 1 part by weight. Specific examples of the silica precursor may be tetramethyl orthosilicate, tetraethyl orthosilicate, tetrabutyl orthosilicate, sodium silicate, sodium metasilicate, or the like, or a mixture of two or more thereof. However, the method is just one example, and is not limited to this manufacturing method.
다음으로, 자성물질을 포함하는 코어층(2a)을 둘러싸는 실리카 쉘층(2b)의 표면은 싸이올기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기를 포함하여 개질될 수 있다. 다만, 싸이올기 또는 카르복실기를 포함할 경우 이러한 작용기와 공유결합할 수 있는 작용기가 그래핀 옥사이드에 포함되어 있어야 되고, 이러한 예로, 카르복실기를 포함하는 실리카 쉘층일 경우 아민기를 포함하는 그래핀 옥사이드 나노시트가 요구되며, 싸이올기를 포함하는 실리카 쉘층일 경우 싸이올기를 포함하는 그래핀 옥사이드 나노시트가 요구될 수 있고, 더 구체적으로 싸이올기를 도입된 나노시트는 싸이올기가 포함된 2-나프탈렌싸이올(2-naphthalenethiol), 1,4-벤젠 디싸이올(1,4-benzene dithiol) 등을 공지의 방법을 통해 그래핀 옥사이드 나노시트에 처리해야 되는 별도의 공정을 거쳐야 하므로, 별도로 공정을 거치지 않고도 공유결합을 시킬 수 있는 아민기를 실리카 쉘층에 포함하는 것이 보다 바람직하다. 구체적으로 아민기(2c)는 그래핀 옥사이드 나노시트상에 포함된 작용기중 의 하나인 카르복실기와 반응하여 아미드 결합을 형성시킴으로써 제1 나노입자(2)와 지지체(1) 간에 우수한 결합력을 구현시킬 수 있다. 구체적으로 도 3은 본 발명의 바람직한 일실시예에 따른 그래핀 옥사이드 나노시트(1)상에 공유결합된 제1 나노입자(2)의 모식도로써, 그래핀 옥사이드 나노시트에 포함된 카르복실기와 제1 나노입자(2) 표면에 포함된 아민기간에 아미드 결합이 형성된 것을 확인할 수 있다.Next, the surface of the silica shell layer 2b surrounding the core layer 2a including the magnetic material may be modified to include one or more functional groups selected from the group consisting of a thiol group, an amine group and a carboxyl group. However, in the case of containing a thiol group or a carboxyl group, a functional group capable of covalently bonding with such a functional group should be included in the graphene oxide. For example, in the case of a silica shell layer containing a carboxyl group, the graphene oxide nanosheet including an amine group is If desired, in the case of a silica shell layer containing a thiol group, a graphene oxide nanosheet including a thiol group may be required, and more specifically, a nanosheet having a thiol group introduced therein may include 2-naphthalene thiol containing a thiol group ( 2-naphthalenethiol), 1,4-benzene dithiol (1,4-benzene dithiol), etc. must be processed in a separate process to be treated to the graphene oxide nanosheets by a known method, sharing without a separate process It is more preferable to include an amine group which can be bonded in a silica shell layer. Specifically, the amine group 2c may react with the carboxyl group, which is one of the functional groups included on the graphene oxide nanosheet, to form an amide bond, thereby realizing excellent binding force between the first nanoparticle 2 and the support 1. have. Specifically, Figure 3 is a schematic diagram of the first nanoparticles (2) covalently bonded on the graphene oxide nanosheets 1 according to a preferred embodiment of the present invention, the carboxyl group included in the graphene oxide nanosheets 1 It can be seen that the amide bond is formed in the amine period contained in the surface of the nanoparticles (2).
실리카 쉘층(2b)의 표면을 싸이올기, 아민기 및 카르복실기 중 어느 하나 이상으로 개질시키는 방법은 공지된 방법을 사용할 수 있으며, 먼저, 아민기를 제공하는 전구체로 N-(3-아크릴옥시-2-하이드록시프로필)-3-아미노프로필트리에톡시실란, N-(3-아크릴옥시-2-하이드록시프로필)-3-아미노프로필트리메톡시실란, N-(3-아크릴옥시-2-하이드록시프로필)-3-아미노프로필트리프로폭시실란, N-(2-아미노에틸-3-아미노프로필)-트리메톡시실란, N-(2-아미노에틸-3-아미노프로필)-트리에톡시실란, 3-아미노프로필트리메톡시실란 및 3-아미노프로필트리에톡시실란 등으로 이루어진 군에서 선택된 어느 하나를 단독 또는 2종이상 병용하여 사용할 수 있다. The method of modifying the surface of the silica shell layer 2b with at least one of a thiol group, an amine group and a carboxyl group may use a known method, and firstly, N- (3-acryloxy-2- as a precursor for providing an amine group. Hydroxypropyl) -3-aminopropyltriethoxysilane, N- (3-acryloxy-2-hydroxypropyl) -3-aminopropyltrimethoxysilane, N- (3-acryloxy-2-hydroxy Propyl) -3-aminopropyltripropoxysilane, N- (2-aminoethyl-3-aminopropyl) -trimethoxysilane, N- (2-aminoethyl-3-aminopropyl) -triethoxysilane, Any one selected from the group consisting of 3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane and the like can be used alone or in combination of two or more thereof.
또한, 카르복실기는 카르복실기를 포함하는 실란 화합물을 통해 도입시킬 수 있으며, 이에 대한 비제한적인 예로써, 카르복시에틸실란트리올 소듐염(carboxyethylsilanetriol sodium salt), 트리에톡시실릴프로필말레암산(triethoxysilylpropylmaleamic acid) 또는 트리메톡시실릴프로필에틸렌 디아민 트리아세트산 소듐염(N-(trimethoxysilylpropyl)ethylene diamine triacetic acid trisodium salt) 등을 1종 또는 2종이상 병용하여 사용할 수 있다. In addition, the carboxyl group may be introduced through a silane compound containing a carboxyl group, and as a non-limiting example, carboxyethylsilanetriol sodium salt, triethoxysilylpropylmaleamic acid or Trimethoxysilylpropylethylene diamine triacetic acid sodium salt (N- (trimethoxysilylpropyl) ethylene diamine triacetic acid trisodium salt) etc. can be used 1 type or in combination of 2 or more types.
또한, 싸이올기는 싸이올-실란기를 포함하는 전구체를 통해 제공될 수 있으며, 바람직하게는 3-머캅토프로필트리메톡시실란(3-mercaptopropylmethoxysilane), 3-머캅토프로필트리에톡시실란(3-mercaptopropylethoxysilane), 11-머캅토운데실트리메톡시실란 (11-mercaptoundecyltrimethoxysilane), 머캅토메틸메틸디에톡시실란 (Mercaptomethylmethyldiethoxysilane), 비스[3-(트리에톡실)프로필]-디설파이드 (Bis[3-(trietoxysilyl)프로필]-디설파이드 등으로 이루어진 군에서 선택된 어느 하나 이상을 단독 또는 2종 이상 병용하여 사용할 수 있다.In addition, the thiol group may be provided through a precursor including a thiol-silane group, preferably 3-mercaptopropyltrimethoxysilane, 3-mercaptopropyltriethoxysilane (3- mercaptopropylethoxysilane), 11-mercaptoundecyltrimethoxysilane, mercaptomethylmethyldiethoxysilane, bis [3- (triethoxyl) propyl] -disulfide (Bis [3- (trietoxysilyl) ) Propyl] -disulfide or the like can be used alone or in combination of two or more.
구체적으로 도 6은 본 발명의 바람직한 일실시예에 포함되는 코어부인 자성물질 나노입자로 사산화삼철 나노입자(도 6a)와 상기 나노입자를 둘러싸고 있는 실리카 쉘층을 포함하는 제1 나노입자(도 6b)의 주사전자현미경 사진으로 코어부에 일정두께로 쉘층이 형성되었음을 확인할 수 있다.Specifically, FIG. 6 is a first nanoparticle including ferric tetraoxide nanoparticles (FIG. 6A) and a silica shell layer surrounding the nanoparticles as magnetic material nanoparticles, which are core parts included in a preferred embodiment of the present invention (FIG. 6B). Scanning electron micrographs of shows that the shell layer was formed at a predetermined thickness in the core portion.
다음으로, 그래핀 옥사이드 나노시트 및/또는 제1 나노입자(2)와 공유결합되어 복합체에 포함되는 제2 나노입자(3)에 대해 설명한다.Next, the second nanoparticles 3 covalently bonded to the graphene oxide nanosheets and / or the first nanoparticles 2 and included in the composite will be described.
구체적으로 도 4는 본 발명의 바람직한 일실시예에 따른 제2 나노입자(3)의 모식도로써, 제2 나노입자(3)는 광열효과를 발휘하는 광열금속(3a)을 포함하며, 광열금속(3a)은 실란기(3b)로 표면이 개질될 수 있으며, 광열금속(3a)은 유기화합물(3c)을 포함할 수 있다. Specifically, Figure 4 is a schematic diagram of the second nanoparticles (3) according to an embodiment of the present invention, the second nanoparticles (3) includes a photothermal metal (3a) exhibiting a photothermal effect, 3a) may be modified with a silane group 3b, and the photothermal metal 3a may include an organic compound 3c.
상기와 같은 제2 나노입자(3)는 도 1에서와 같이 그래핀 옥사이드 나노시트에 결합(도 1의 3 경우임)하거나 그래핀 옥사이드 나노시트와 제1 나노입자(2)에 동시에 결합(도 1의 P)하거나 제1 나노입자(2)와 결합(도 1의 Q)할 수 있다. As described above, the second nanoparticles 3 are bonded to the graphene oxide nanosheets as shown in FIG. 1 (in the case of 3 in FIG. 1) or simultaneously bonded to the graphene oxide nanosheets and the first nanoparticles 2 (FIG. 1) may be combined with the first nanoparticle 2 (Q in FIG. 1).
먼저, 광열금속(3a)은 금, 은, 팔라듐, 백금, 구리 및 알루미늄으로 이루어진 군에서 선택된 어느 하나 이상을 포함할 수 있으며, 바람직하게는 광열효과 측면에서 금을 사용할 수 있다. 상기 광열금속(3a)의 형상은 본 발명에서는 특별히 한정하지는 않으며, 구형, 로드형, 성상형 등일 수 있고, 바람직하게는 광열효과 및 제조용이성 측면에서 로드형일 수 있다. 광열금속의 직경은 본 발명에서 특별히 한정하지 않으며, 구형일 때의 직경, 로드형일 때의 종횡비(aspect ratio)는 광열금속에 조사되는 레이져의 파장과 관계가 있어 본 발명에 따른 나노복합체를 사용하려는 용도 등에 따라 레이져 파장을 달리할 경우 상기 광열금속의 직경이나 종횡비를 달리 변경하여 사용할 수 있다. 예를 들어, 광열금속이 금이고, 종횡비가 3 ~ 4인 로드형인 경우 근적외선의 파장 780nm에서 우수한 광열효과를 발현하고, 다른 파장대에서는 광열효과가 저하될 수 있다. 구체적으로 도 7은 본 발명에 따른 바람직한 일시예에 포함되는 제2 나노입자에 포함되는 금 나노로드의 주사전자현미경 사진으로 로드형의 금나노로드를 확인할 수 있다.First, the photothermal metal 3a may include any one or more selected from the group consisting of gold, silver, palladium, platinum, copper, and aluminum, and gold may be preferably used in view of photothermal effects. The shape of the photothermal metal 3a is not particularly limited in the present invention, and may be a spherical shape, a rod shape, a star shape, or the like, and preferably may be rod-shaped in terms of light heat effect and ease of manufacture. The diameter of the photothermal metal is not particularly limited in the present invention, and the diameter in the spherical shape and the aspect ratio in the rod shape are related to the wavelength of the laser irradiated to the photothermal metal, thereby to use the nanocomposite according to the present invention. When the laser wavelength is changed according to the use, the diameter or aspect ratio of the photothermal metal may be changed. For example, when the light-heat metal is gold and the rod type having an aspect ratio of 3 to 4, the light-heat effect may be excellent at a wavelength of 780 nm of near infrared rays, and the light-heat effect may be lowered at other wavelengths. Specifically, Figure 7 can be confirmed the rod-type gold nanorods by scanning electron micrograph of the gold nanorods contained in the second nanoparticles included in the preferred embodiment according to the present invention.
다음으로, 제2 나노입자(3)에 포함된 광열금속(3a)은 실란기(3b), 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기를 포함하여 표면이 개질 될 수 있는데, 상기와 같은 작용기로 표면을 개질시킴으로써 그래핀 옥사이드 나노시트에 포함된 히드록시기, 카르복실기 및/또는 제1 나노입자(2)에 포함된 실리카 쉘층 및/또는 쉘층에 포함된 아민기 등의 작용기와 공유결합을 형성시킬 수 있다. 구체적으로 광열금속에 포함된 실란기는 그래핀 옥사이드 나노시트에 포함된 히드록시기 및/또는 카르복시기와 공유결합을 할 수 있으며, 광열금속에 포함된 아민기는 그래핀 옥사이드 나노시트에 포함된 카르복실기와 아미드 결합을 할 수 있으며, 광열금속에 포함된 카르복실기는 아민기가 도입된 그래핀 옥사이드 나노시트에 포함된 아민기와 아미드 결합을 할 수 있다. 이때, 아민기를 그래핀 옥사이드 나노시트에 도입시키는 방법은 공지 관용의 기술 및 이때 사용하는 통상적인 아민화합물을 사용할 수 있다. Next, the photothermal metal 3a included in the second nanoparticle 3 may include any one or more functional groups selected from the group consisting of a silane group 3b, an amine group, and a carboxyl group. By modifying the surface with the same functional group, a covalent bond is formed with a functional group such as a hydroxy group, a carboxyl group, and / or a silica shell layer included in the graphene oxide nanosheets and / or an amine group included in the shell layer. You can. Specifically, the silane group included in the photothermal metal may covalently bond with the hydroxy group and / or carboxyl group included in the graphene oxide nanosheet, and the amine group included in the photothermal metal may form an amide bond with the carboxyl group included in the graphene oxide nanosheet. The carboxyl group included in the photothermal metal may have an amide bond with the amine group included in the graphene oxide nanosheet into which the amine group is introduced. In this case, the method of introducing the amine group into the graphene oxide nanosheets may use a known conventional technique and a conventional amine compound used at this time.
또한, 광열금속에 포함된 실란기는 제1 나노입자의 실리카 쉘층과 공유결합을 할 수 있으며, 광열금속에 포함된 아민기는 제1 나노입자의 실리카 쉘층에 도입된 카르복실기와 아미드 결합을 할 수 있으며, 광열금속에 포함된 카르복실기는 제1 나노입자의 실리카 쉘층에 도입된 아민기와 아미드 결합을 할 수 있다. In addition, the silane group included in the photothermal metal may be covalently bonded to the silica shell layer of the first nanoparticles, the amine group included in the photothermal metal may have an amide group and a carboxyl group introduced into the silica shell layer of the first nanoparticle, The carboxyl group included in the photothermal metal may have an amide bond with the amine group introduced into the silica shell layer of the first nanoparticle.
상기 실란기는 실란기를 포함하는 전구체를 통해 광열금속(3a) 표면에 도입될 수 있는데, 상기 전구체는 통상적으로 금속의 표면을 실란기로 기능화 시에 사용되는 전구체의 경우 제한없이 사용될 수 있으며, 바람직하게는 싸이올-실란기를 포함하는3-머캅토프로필트리메톡시실란(3-mercaptopropylmethoxysilane), ~3-머캅토프로필트리에톡시실란(3-mercaptopropylethoxysilane), 11-머캅토운데실트리메톡시실란 (11-mercaptoundecyltrimethoxysilane), 머캅토메틸메틸디에톡시실란 (Mercaptomethylmethyldiethoxysilane), 비스[3-(트리에톡실)프로필]-디설파이드 (Bis[3-(trietoxysilyl)프로필]-디설파이드 등으로 이루어진 군에서 선택된 어느 하나 이상을 포함하여 사용할 수 있다. 이때, 상기 전구체의 싸이올기가 광열금속과 결합할 수 있으며, 이를 통해 광열금속 표면이 실란기로 개질될 수 있다. The silane group may be introduced to the surface of the photothermal metal 3a through a precursor including a silane group, and the precursor may be used without limitation in the case of a precursor used when functionalizing a surface of a metal into a silane group. 3-mercaptopropyltrimethoxysilane, 3-mercaptopropylethoxysilane, 11-mercaptodecyltrimethoxysilane containing a thiol-silane group (11 at least one selected from the group consisting of -mercaptoundecyltrimethoxysilane, mercaptomethylmethyldiethoxysilane, bis [3- (triethoxysil) propyl] -disulfide, and the like. In this case, the thiol group of the precursor may be combined with the photothermal metal, through which the photothermal metal surface may be modified with a silane group.
또한, 아민기를 제공하는 전구체로는 싸이올기와 아민기를 포함하는 화합물이 바람직하며, 이러한 비제한적인 예로써, 2-아미노--머캅토-1,3,4-씨아다졸(2-Amino-5-mercapto-1,3,4-thiadiazole), 씨아구아닌(Thioguanine), 시스테인(Cysteine), 페니실라민(Penicillamine), 4-아미노-2-머탑토부틸산(4-Amino-2-mercaptobutyric acid), 시스테아민(cysteamine) 등으로 이루어진 군에서 선택된 어느 하나를 단독 또는 2종이상 병용하여 사용할 수 있고 이를 통해 아민기를 광열금속에 도입할 수 있다. Further, as a precursor for providing an amine group, a compound containing a thiol group and an amine group is preferable. As a non-limiting example, 2-amino-mercapto-1,3,4-cidazole (2-Amino-5 -mercapto-1,3,4-thiadiazole, Thiaguanine, Cysteine, Penicillamine, 4-Amino-2-mercaptobutyric acid , Cysteamine, etc. may be used alone or in combination of two or more selected from the group consisting of, through which the amine group may be introduced into the photothermal metal.
또한, 카르복실기를 제공하는 전구체로 카르복실기와 싸이올기를 포함하는 화합물이 바람직하며 머캅토운데실산(mercaptoundecanoic acid), 3-머캅토프로피오닉산(3-mercaptopropionic acid), 3-머캅토피루빅산(3-mercaptopyruvic acid), 2-머캅토아세테이트(2-mercaptoacetate), 시스테인(Cysteine), 페니실라민(Penicillamine), 4-아미노-2-머탑토부틸산(4-Amino-2-mercaptobutyric acid) 등을 단독 또는 2종이상 병용하여 사용할 수 있고 이를 통해 카르복실기를 광열금속에 도입할 수 있다. In addition, as a precursor for providing a carboxyl group, a compound containing a carboxyl group and a thiol group is preferable, and a mercaptoundecanoic acid, 3-mercaptopropionic acid, 3-mercaptopyruvic acid (3 -mercaptopyruvic acid), 2-mercaptoacetate, cysteine, penicillamine, 4-amino-2-mercaptobutyric acid It can be used alone or in combination of two or more, through which a carboxyl group can be introduced into the photothermal metal.
상기의 전구체들을 이용하여 광열금속 표면을 개질화 시키는 구체적인 방법은 공지 관용의 통상적인 방법을 사용할 수 있으며, 광열금속(3a)에 충분한 양을 투입할 경우 혼합비율은 본 발명에서 특별히 한정하지 않는다.As a specific method of modifying the photothermal metal surface using the precursors, a conventional method known in the art may be used. When a sufficient amount is added to the photothermal metal 3a, the mixing ratio is not particularly limited in the present invention.
다음으로 제2 나노입자(3)는 유기화합물(3c)을 포함할 수 있다. 유기화합물(3c)은 용매 속에서 광열금속의 응집을 막고, 분산성을 높여 그래핀 옥사이드 나노시트에 제2 나노입자의 접근성을 높이며, 수성용매에서의 안정성을 확보의 기능을 담당한다. 상기 유기화합물(3c)은 광열금속(3a)과 결합력이 우수한 작용기를 포함하는 유기화합물일 수 있으며, 바람직하게는 티올기를 포함하는 유기화합물일 수 있고, 구체적으로 티올기를 포함하는 분자량이 500 ~ 50,000인 메톡시폴리에틸렌글리콜-티올(mPEG-SH), 올레일 아민 (Oleylamine), 폴리에틸렌이민(polyethylene imine) 등으로 이루어진 군에서 선택된 어느 하나 이상의 물질과 결합된 형태일 수 있다. 상기 유기화합물(3c)은 광열금속(3a)에 충분한 양으로 가해질 수 있으며, 제조 시 혼합비율은 본 발명에서 특별히 한정하지 않는다.Next, the second nanoparticle 3 may include an organic compound 3c. The organic compound 3c prevents the aggregation of photothermal metals in a solvent, increases dispersibility, increases the accessibility of the second nanoparticles to the graphene oxide nanosheets, and plays a role of securing stability in an aqueous solvent. The organic compound 3c may be an organic compound including a functional group having excellent bonding force with the photothermal metal 3a, preferably an organic compound including a thiol group, and specifically, a molecular weight including a thiol group is 500 to 50,000. Phosphorus methoxy polyethylene glycol-thiol (mPEG-SH), oleyl amine (Oleylamine), polyethylene imine (polyethylene imine) and the like may be combined with any one or more materials selected from the group consisting of. The organic compound 3c may be added to the photothermal metal 3a in a sufficient amount, and the mixing ratio in manufacturing is not particularly limited in the present invention.
이상으로 상술한 그래핀 옥사이드 나노시트를 포함한 지지체(1), 제1 나노입자(2), 제2 나노입자(3)의 나노복합체 내에서의 함량은 본 발명에서 특별히 한정하지 않으며, 자기장에서 분리/수집될 수 있을 정도의 자성을 발현하고, 목적하는 광열효과를 발생시킬 정도로 지지체(1)에 포함되는 경우 제한은 없으나, 바람직하게는 그래핀 옥사이드 나노시트를 포함하는 지지체(1) 100 중량부에 대해 제1 나노입자(2)를 10 ~ 100 중량부, 제2 나노입자를 10 ~ 100중량부 포함할 수 있다. 만일 어느 하나 이상의 나노입자가 상기 범위에서 하한값 미만으로 포함될 경우 효과가 미약한 문제점이 있을 수 있으며, 상한값을 초과하여 포함될 경우 나노복합체의 직경, 부피가 커져 나노복합체를 생체에 사용하는 등 특정 용도에서는 사용에 제약이 있을 수 있다. 본 발명에 따른 나노복합체의 직경이나 부피 등의 크기의 경우 본 발명에서는 특별히 한정하지 않으며, 사용하려는 용도, 발현이 요구되는 효과의 정도를 고려하여 달리 설계할 수 있다.As described above, the content in the nanocomposite of the support (1), the first nanoparticle (2), and the second nanoparticle (3) including the graphene oxide nanosheets described above is not particularly limited in the present invention, and is separated from the magnetic field. There is no limitation in the case of being included in the support 1 so as to express the magnetism that can be collected and generate a desired photothermal effect, but preferably 100 parts by weight of the support 1 including the graphene oxide nanosheets. 10 to 100 parts by weight of the first nanoparticles 2, and 10 to 100 parts by weight of the second nanoparticles. If any one or more of the nanoparticles are included in the above range below the lower limit, there may be a weak effect, and if included in excess of the upper limit, the diameter, volume of the nanocomposite is increased in certain applications, such as using the nanocomposite in a living body There may be restrictions on use. In the case of the size of the diameter or volume of the nanocomposite according to the present invention is not particularly limited in the present invention, may be designed in consideration of the intended use, the degree of effect required expression.
본 발명의 바람직한 일실시예에 따르면, 상기와 같은 그래핀 옥사이드 나노복합체는 단층의 그래핀 옥사이드 나노시트를 포함하는 지지체; 사산화삼철(Fe3O4)을 포함하는 자성물질을 포함하는 코어층 및 상기 코어층을 둘러싸고 아민기로 표면개질된 실리카 쉘층을 포함하고 상기 그래핀 옥사이드 나노시트상에 공유결합하여 포함되는 제1 나노입자; 및 표면이 실란기로 개질된 종횡비(aspect ratio)가 3 ~ 4인 금나노로드를 포함하는 광열금속입자를 포함하고, 상기 그래핀 옥사이드 나노시트 및 제1 나노입자 중 어느 하나 이상과 공유결합하여 포함되는 제2 나노입자;를 포함할 수 있으며, 이에 따라 하기에 상술되는 것과 같이 광열효과에서 우수한 상승효과를 발현할 수 있고, 그래핀 옥사이드 나노복합체의 분리/수집성을 보다 향상시킬 수 있다.According to a preferred embodiment of the present invention, the graphene oxide nanocomposite as described above is a support comprising a single layer of graphene oxide nanosheets; A first nano-containing core layer comprising a magnetic material containing triiron tetraoxide (Fe 3 O 4 ) and a silica shell layer surrounding the core layer and surface-modified with an amine group and covalently included on the graphene oxide nanosheets. particle; And photothermal metal particles including gold nanorods having an aspect ratio of 3 to 4 whose surface is modified by a silane group, and are covalently bonded to any one or more of the graphene oxide nanosheets and the first nanoparticles. The second nanoparticles may be included, and thus may express an excellent synergistic effect in the photothermal effect as described below, and may further improve the separation / collection of the graphene oxide nanocomposites.
이러한 본 발명에 따른 그래핀 옥사이드 나노복합체는 나노복합체에 포함되는 그래핀 옥사이드 나노시트와 제2 나노입자의 시너지로 인해 우수한 광열효과를 발현함에 따라 파장이 780nm이고, 세기가 2mW/cm2인 근적외선(NIR) 레이저를 조사시 하기의 조건 (1) 내지 (3)을 만족할 수 있다.The graphene oxide nanocomposite according to the present invention exhibits excellent photothermal effects due to the synergy between the graphene oxide nanosheets and the second nanoparticles included in the nanocomposite, with a wavelength of 780 nm and a near infrared ray having an intensity of 2 mW / cm 2 . When irradiating a (NIR) laser, the following conditions (1) to (3) can be satisfied.
(1) 레이저 조사 100초 경과 후 증가된 온도가 레이저 조사 전에 비해 6℃ 이상이고, (2) 레이저 조사 300초 경과 후 증가된 온도가 레이저 조사 전에 비해 20℃ 이상이며, (3) 레이져 조사 900 초 경과 후 증가된 온도가 레이저 조사 전에 비해 38℃ 이상임.(1) The temperature increased after 100 seconds of laser irradiation is 6 ° C or higher than before laser irradiation, (2) The temperature increased after 300 seconds of laser irradiation is 20 ° C or higher than before laser irradiation, and (3) The laser irradiation 900 After an elapse of time the increased temperature is above 38 ° C compared to before laser irradiation.
구체적으로 도 11은 본 발명의 바람직한 일실시예에 따른 나노복합체에 레이져 조사시 시간당 온도증가를 나타낸 그래프로써, 그래핀 옥사이드 나노시트만 존재하는 경우에도 레이저 조사 시간이 길어질수록 온도가 증가하여 그래핀 옥사이드 나노시트 자체도 광열효과가 있음을 확인할 수 있다. 또한, 그래핀 옥사이드 나노시트에 제1 나노입자가 포함된 경우(도 11의 제1나노입자/그래핀옥사이드) 그래핀 옥사이드 나노시트만 포함된 경우와 비교시 시간에 따른 온도 증가가 거의 동일함을 알 수 있어 광열금속이 아닌 자성입자가 포함된 제1 나노입자의 경우 광열효과에는 영향을 미치지 않음을 알 수 있다. Specifically, Figure 11 is a graph showing the temperature increase per hour when the laser irradiation to the nanocomposite according to an embodiment of the present invention, even if only graphene oxide nanosheets are present as the laser irradiation time increases the temperature increases It can be seen that the oxide nanosheets themselves have a photothermal effect. In addition, when the graphene oxide nanosheets contain the first nanoparticles (first nanoparticles / graphene oxide of Figure 11) compared with the case that contains only the graphene oxide nanosheets, the temperature increase with time is almost the same. It can be seen that the first nanoparticles containing magnetic particles other than the photothermal metal do not affect the photothermal effect.
한편, 도 11에서 금 나노로드(제2 나노입자)에 레이저를 조사시에 시간에 따른 온도 변화가 커서 금에 광열효과가 있는 것을 확인할 수 있으나 본 발명에 따른 나노복합체(제1 나노입자/제2 나노입자/그래핀옥사이드)에 레이저를 조사시 금 나노로드 단독으로 있을 때 보다 광열효과에 있어 월등히 뛰어남을 알 수 있다. 이는 본 발명에 따른 나노복합체는 광열효과에 있어 각 구성 즉 그래핀 옥사이드 나노시트와 금나노로드의 효과 합을 넘는 시너지 효과를 발휘하기 때문이며, 레이저가 조사되는 시간이 길어질수록 이러한 시너지 효과는 현저하기 증가한다는 것을 도 11을 통해 확인할 수 있다. 이러한 결과는 상술한 그래핀 옥사이드 나노시트가 가지고 있는 열전도도, 광투과도, 자체의 광열기능으로 인해 광열효과가 보다 더 증폭될 수 있다는 것을 입증하고 있다.On the other hand, in Figure 11, the gold nanorods (second nanoparticles) when irradiating a laser with a large temperature change over time, it can be seen that there is a photothermal effect on the gold nanocomposite according to the present invention (first nanoparticles / 2 nanoparticles / graphene oxide) when the laser is irradiated with gold nanorods alone can be seen to be superior in the photothermal effect. This is because the nanocomposite according to the present invention exhibits a synergistic effect that exceeds the sum of the effects of the respective structures, that is, graphene oxide nanosheets and gold nanorods, in light-heating effect, and the synergistic effect is remarkable as the laser irradiation time increases. It can be seen from Figure 11 that the increase. These results demonstrate that the photothermal effect can be further amplified by the thermal conductivity, the light transmittance, and the photothermal function of the graphene oxide nanosheets described above.
한편, 본 발명에 따른 나노복합체는 (1) 자성을 띠는 제1 나노입자를 포함하는 용액에 그래핀 옥사이드 나노시트를 투입하여 제1 복합체를 제조하는 단계; 및 (2) 상기 복합체를 광열효과를 발현하는 제2 나노입자가 포함된 용액에 투입하여 제2 복합체를 제조하는 단계;를 포함하여 제조될 수 있다.On the other hand, the nanocomposite according to the present invention comprises the steps of (1) preparing a first composite by injecting graphene oxide nanosheets into a solution containing the first nanoparticles having a magnetic; And (2) preparing the second complex by adding the complex to a solution containing the second nanoparticles expressing the photothermal effect.
구체적으로 도 12는 본 발명의 바람직한 일실시예에 따른 제조공정 모식도로써, 먼저, (1) 단계로 자성을 띠는 제1 나노입자를 포함하는 용액에 그래핀 옥사이드 나노시트를 투입하여 제1 복합체를 제조하는 단계를 포함한다.Specifically, FIG. 12 is a schematic diagram of a manufacturing process according to an embodiment of the present invention. First, a graphene oxide nanosheet is added to a solution including first nanoparticles having magnetic properties in step (1). It comprises the step of preparing.
구체적으로 그래핀 옥사이드 나노시트 100 중량부에 대해 자성을 띠는 제1 나노입자를 포함하는 용액을 10 ~ 100 중량부 혼합하여 20 ~ 30℃에서 10 ~ 24시간 교반하여 제1 복합체를 제조할 수 있으며, 이외에 커플링제, 커플링 보조제를 그래핀 옥사이드 나노시트 100 중량부에 대해 10 ~ 100 중량부 더 포함할 수 있다. 만일 제1 나노입자를 포함하는 용액이10 중량부 미만으로 포함될 경우 그래핀 옥사이드 나노시트에 결합하는 제1 나노입자의 함량이 너무 적어 목적하는 자성을 발휘할 수 없음에 따라 나노복합체의 분리/수집이 어려울 수 있는 문제점이 있으며, 100중량부를 초과할 경우 결합되지 않고 존재하는 제1 나노입자의 양이 늘어나 비효율적일 수 있다. Specifically, the first composite may be prepared by mixing 10 to 100 parts by weight of a solution containing the first nanoparticles having magnetic properties with respect to 100 parts by weight of graphene oxide nanosheets and stirring at 20 to 30 ° C. for 10 to 24 hours. In addition, the coupling agent, the coupling aid may further comprise 10 to 100 parts by weight based on 100 parts by weight of the graphene oxide nanosheets. If the solution containing the first nanoparticles is included in less than 10 parts by weight, the content of the first nanoparticles bound to the graphene oxide nanosheets is too small to exert the desired magnetism, thus the separation / collection of the nanocomposites is difficult. There may be a problem that may be difficult, and when the amount exceeds 100 parts by weight, the amount of the first nanoparticles that are not bound and increases may be inefficient.
상기 제1 나노입자를 포함하는 용액의 용매는 물, 에탄올 등의 유기용매일 수 있으며, 상기 용매는 제1 나노입자에 물리적, 화학적 영향이 없고 제1 나노입자를 잘 분산시킬 수 있는 용매인 경우 제한없이 사용될 수 있고, 나노복합체에 포함시킬 제1 나노입자의 함량을 고려하여 제1 나노입자가 용매에 포함될 수 있으며, 목적에 따라 그 함량은 달라질 수 있는 바 본 발명에서 특별히 한정하지 않는다. 또한, 상기 커플링제는 물을 용매로 사용할 경우 EDC(1-ethyl-3-(3-dimethylamini-propyl)carbodiimide) 등을 사용할 수 있고, 커플링 보조제로서 NHS(N-hydroxysuccinimide), NHSS(N-hydroxysulfosuccinimide) 등을 사용할 수 있으나 이에 제한되는 것은 아니다. When the solvent of the solution containing the first nanoparticles may be an organic solvent such as water, ethanol, the solvent is a solvent that can disperse the first nanoparticles well without physical and chemical effects on the first nanoparticles It can be used without limitation, the first nanoparticles may be included in the solvent in consideration of the content of the first nanoparticles to be included in the nanocomposite, the content may vary depending on the purpose is not particularly limited in the present invention. In addition, the coupling agent may use EDC (1-ethyl-3- (3-dimethylamini-propyl) carbodiimide) and the like when using water as a solvent, NHS (N-hydroxysuccinimide), NHSS (N- hydroxysulfosuccinimide) and the like, but is not limited thereto.
상기 커플링제는 카르복시기와 아민기가 아미드 결합(-CONH-)을 형성하는 역할을 하며, 상기 커플링 보조제는 아미드 결합을 형성할 때 효율을 높일 수 있도록 도와주는 역할을 한다. 이에 따라 (1) 단계는 제1 나노입자의 실리카 쉘층 표면에 포함된 싸이올기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기와 그래핀 옥사이드 나노시트에 포함된 히드록시기 및/또는 카르복시기 간에 아미드 결합 등의 공유결합을 형성시킬 수 있고 이에 따라 제1 복합체에 포함된 제1 나노입자가 그래핀 옥사이드 나노시트에서 쉽게 분리되지 않도록 강한 화학적 결합력을 발현시킬 수 있다. The coupling agent serves to form an amide bond (-CONH-) with the carboxyl group and the amine group, and the coupling aid serves to increase the efficiency when forming the amide bond. Accordingly, the step (1) is an amide between any one or more functional groups selected from the group consisting of a thiol group, an amine group and a carboxyl group contained on the surface of the silica shell layer of the first nanoparticle, and a hydroxyl group and / or carboxyl group included in the graphene oxide nanosheet. Covalent bonds such as bonds may be formed, and thus, the first nanoparticles included in the first complex may express a strong chemical bonding force so that they are not easily separated from the graphene oxide nanosheets.
상기 자성을 띠는 제1 나노입자는 자성물질을 둘러싸고 있는 실리카 쉘층을 포함하는 코어쉘 구조로써, 실리카 쉘층의 표면이 싸이올기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기를 포함할 수 있다. 또한, 상기 그래핀 옥사이드 나노시트는 우수한 효과의 발현을 위해 단층인 그래핀 옥사이드 나노시트일 수 있다. 제1 나노입자 및 그래핀 옥사이드 나노시트에 대한 구체적인 설명, 이의 제조방법 및 공유결합이 가능한 작용기의 설명은 상술한 것과 같은바, 이하 생략하기로 한다.The magnetic first nanoparticle is a core shell structure including a silica shell layer surrounding a magnetic material, and the surface of the silica shell layer may include any one or more functional groups selected from the group consisting of a thiol group, an amine group, and a carboxyl group. have. In addition, the graphene oxide nanosheets may be a single layer graphene oxide nanosheets for the expression of excellent effects. Detailed description of the first nanoparticles and the graphene oxide nanosheets, a method of preparing the same, and a description of functional groups capable of covalent bonding are the same as described above, and will be omitted below.
다음으로 (2) 단계로써, 상기 제1 복합체를 광열효과를 발현하는 제2 나노입자가 포함된 용액에 투입하여 제2 복합체를 제조하는 단계;를 포함한다.Next, as a step (2), the step of preparing a second complex by adding the first complex to a solution containing the second nanoparticles expressing the photothermal effect.
상기 제1 복합체는 (1) 단계를 통해 바람직하게는 에탄올 등 유기용매에 분산된 상태일 수 있는데, 제1 복합체가 포함된 용액에 제2 나노입자를 포함하는 용액을 혼합하여 제2 복합체를 제조할 수 있다. The first complex may be in a dispersed state in an organic solvent, such as ethanol, preferably through step (1), to prepare a second complex by mixing a solution including second nanoparticles in a solution including the first complex. can do.
상기 (2) 단계는 바람직하게는 제1 복합체 100 중량부에 대해 제2 나노입자를 10 ~ 100 중량부 혼합할 수 있으며, 상기와 같이 혼합될 수 있다면 상기 제1 복합체를 포함하는 용액의 농도, 제2 나노입자를 포함하는 용액의 농도는 변경하여 실시할 수 있다. 만일 제2 나노입자가 10 중량부 미만으로 투입되는 경우 최종 제조되는 나노복합체 내에 포함된 광열금속을 포함하는 제2 나노입자의 함량이 부족하여 목적하는 광열효과 발현에 미흡할 수 있고, 100 중량부를 초과하여 포함되는 경우 제1 복합체와 결합되지 못하고 미결합된 상태의 제2 나노입자의 양이 많아져 공정이 비효율적으로 되는 문제점이 있을 수 있다. 상기 (2) 단계는 20 ~ 30℃에서 10 ~ 24시간 교반을 통해 제2 복합체를 제조할 수 있으나 이에 제한되는 것은 아니다.The step (2) is preferably 10 to 100 parts by weight of the second nanoparticles with respect to 100 parts by weight of the first complex, if it can be mixed as described above the concentration of the solution containing the first complex, The concentration of the solution containing the second nanoparticles can be changed. If the second nanoparticles are added in less than 10 parts by weight, the content of the second nanoparticles including the photothermal metals contained in the nanocomposite to be manufactured may be insufficient and thus may not be sufficient to express a desired photothermal effect, and 100 parts by weight. When included in excess, the amount of the second nanoparticles that are not bonded to the first composite and the unbound state may increase, resulting in an inefficient process. Step (2) may be prepared a second composite through agitation for 10 to 24 hours at 20 ~ 30 ℃ but is not limited thereto.
상기 제2 나노입자는 실란기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기로 표면개질된 광열 금속 나노입자일 수 있으며, 이에 대한 구체적인 설명은 상술한 것과 같고, 공지 관용의 기술을 사용할 수 있는 바, 이하 생략하기로 한다.The second nanoparticles may be photothermal metal nanoparticles surface-modified with one or more functional groups selected from the group consisting of a silane group, an amine group, and a carboxyl group, and the detailed description thereof is the same as described above, and a known conventional technique may be used. As can be, will be omitted below.
상기 (2) 단계는 제1 복합체에 포함된 제1 나노입자의 실리카 쉘층에 포함된 실란기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기; 및 그래핀 옥사이드 나노시트에 포함된 히드록시기 및 카르복실기 중 어느 하나 이상의 작용기; 중 어느 하나 이상의 작용기와 광열 금속 나노입자 표면의 실란기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기 간에 공유결합을 형성시킴으로써 제2 나노입자가 제1 복합체에서 쉽게 분리되지 않도록 강한 화학적 결합력을 발현시킬 수 있다.Step (2) may be any one or more functional groups selected from the group consisting of a silane group, an amine group and a carboxyl group included in the silica shell layer of the first nanoparticles included in the first composite; And a functional group of any one or more of a hydroxyl group and a carboxyl group included in the graphene oxide nanosheets. Strong chemical bonding force to prevent the second nanoparticles from being easily separated from the first complex by forming a covalent bond between any one or more of the functional groups and any one or more functional groups selected from the group consisting of silane groups, amine groups and carboxyl groups on the surface of the photothermal metal nanoparticles Can be expressed.
상기 공유결합되는 작용기의 조합, 그 중에서 아미드 결합을 시키는 방법은 상술한 바와 같은 바 이하 생략한다. The combination of the covalently bonded functional groups, and the method of making an amide bond, are omitted below as described above.
한편, 본 발명은 본 발명에 따른 나노복합체를 포함하는 암세포 진단용 그래핀 옥사이드 나노 복합체를 포함한다. On the other hand, the present invention includes a graphene oxide nanocomposite for cancer cell diagnostics comprising a nanocomposite according to the present invention.
상기 암세포 진단용 복합체는 본 발명에 따른 나노복합체 이외에 표적물질인 암세포, 특히 혈액내 존재하는 전이 암세포와 바인딩할 수 있는 리셉터 및/또는 리간드를 포함함으로써 나노복합체가 목적하는 전이 암세포에 결합한 후 자기력에 의해 암세포를 분리/수집을 통해 암세포 유무를 진단할 수 있고, 또는 특정한 형광물질 등의 식별표지를 나노복합체에 바인딩시켜 이를 통해 암세포 유무를 진단할 수도 있다. 암세포 유무의 진단은 혈액의 채취를 통해 수행될 수 있으며, 채취된 혈액에 자기장 형성 또는 공지의 방법을 통한 형광물질을 발색을 통해 암세포 유무를 확인할 수 있다.The cancer cell diagnostic complex includes a receptor and / or a ligand capable of binding to a target cancer cell, in particular, a metastatic cancer cell present in the blood, in addition to the nanocomposite according to the present invention, after the nanocomposite binds to the desired metastatic cancer cell by magnetic force. Cancer cells can be diagnosed by separating / collecting cancer cells, or by identifying markers such as specific fluorescent substances on nanocomposites to diagnose cancer cells. The diagnosis of cancer cells may be performed by collecting blood, and the presence or absence of cancer cells may be confirmed by forming a magnetic field in the collected blood or developing fluorescent materials through known methods.
본 발명에 따른 암세포 진단용 복합체에 포함될 수 있는 리셉터 및/또는 리간드는 통상적으로 암세포 클리닝에 사용되는 리간드나 리셉터를 사용할 수 있으며, 본 발명에서는 이에 대해 특별히 한정하지 않고, 리셉터 및/또는 리간드를 복합체에 바인딩시키는 방법은 공지관용의 방법을 사용할 수 있고, 복합체에 포함되는 함량 역시 본 발명에서 한정하지 않는다. Receptors and / or ligands that can be included in the cancer cell diagnostic complex according to the present invention can be used ligands or receptors that are commonly used for cancer cell cleaning, the present invention is not particularly limited to this, the receptor and / or ligands in the complex The binding method may be a known conventional method, and the content contained in the composite is not limited in the present invention.
또한, 본 발명은 본 발명에 따른 나노복합체를 포함하는 암세포 치료용 그래핀 옥사이드 나노 복합체를 포함한다. In addition, the present invention includes a graphene oxide nanocomposite for treating cancer cells comprising a nanocomposite according to the present invention.
암세포의 치료용 복합체는 본 발명에 따른 나노복합체 이외에 표적물질인 암세포, 특히 혈액내 존재하는 전이 암세포와 바인딩할 수 있는 리셉터 및/또는 리간드를 포함함으로써 나노복합체가 목적하는 전이 암세포에 결합한 후 자기력에 의해 암세포를 분리/수집 후 레이저를 가해 광열효과를 발현시킴으로써 표적물질을 파괴, 제거할 수 있다. 또한, 본 발명에 따른 나노복합체에 포함된 제1 나노입자는 자성 나노물질를 포함하는데, 자성 나노물질은 고주파에 의해 열을 발생시키는 특성이 있으므로, 레이저와 동시에 고주파를 가할 시 발열효과가 더 커져 표적물질인 암세포의 파괴, 제거를 보다 극대화 시킬 수 있다.The therapeutic complex of cancer cells, in addition to the nanocomposite according to the present invention, includes a receptor and / or a ligand capable of binding to target cancer cells, in particular, metastatic cancer cells present in the blood, so that the nanocomposite binds to the desired metastatic cancer cells and is then subjected to magnetic force. By separating and collecting cancer cells, by applying a laser to express the photothermal effect, the target material can be destroyed and removed. In addition, the first nanoparticles included in the nanocomposite according to the present invention include a magnetic nanomaterial, and since the magnetic nanomaterial has a property of generating heat by high frequency, the heating effect is increased when the high frequency is simultaneously applied with a laser. It can maximize the destruction and removal of cancer cells as a substance.
이에 따라 암세포 치료용 복합체는 암치료에 있어 종래의 방법인 방사선 치료에 비해 생체에 무해하고, 고통이 없으며, 특정 세포만을 분리/제거 시킴으로써 암세포/정상세포 구별 없이 무차별적으로 세포를 죽이는 종래의 방법에 비해 보다 효율적일 수 있다. Accordingly, the cancer cell treatment complex is harmless to the living body, has no pain, and kills cells indiscriminately without distinguishing cancer cells or normal cells by separating / removing only specific cells, compared to conventional methods of cancer therapy. Can be more efficient than
본 발명에 따른 암세포 치료용 복합체에 포함될 수 있는 리셉터 및/또는 리간드는 통상적으로 암세포 클리닝에 사용되는 리간드나 리셉터를 사용할 수 있으며, 본 발명에서는 이에 대해 특별히 한정하지 않고, 리셉터 및/또는 리간드를 복합체에 바인딩시키는 방법은 공지관용의 방법을 사용할 수 있고, 복합체에 포함되는 함량 역시 본 발명에서 한정하지 않는다.Receptors and / or ligands that may be included in the complex for treating cancer cells according to the present invention may be used ligands or receptors commonly used for cancer cell cleaning, and the present invention is not particularly limited thereto, and the receptor and / or ligand may be complexed. The binding method may be a known conventional method, and the content of the composite is not limited in the present invention.
본 발명에 따른 암세포 진단용 또는 치료용 그래핀 옥사이드 나노복합체는 임상투여 시에 주사제를 통해 혈관으로 주입될 수 있으며, 주사제 조성물은 본 발명에 따른 암세포 진단용 또는 치료용 그래핀 옥사이드 나노복합체 이외에 에틸올레이트와 같은 주사 가능한 에스테르, 생리 식염수 등을 포함할 수 있고, 안정성을 증가시키기 위하여 글루코스, 수크로스 또는 덱스트란과 같은 카보하이드레이트, 아스코르브 산(ascorbic acid) 또는 글루타치온과 같은 항산화제(antioxidants), 킬레이팅 물질(chelating agents), 저분자 단백질 또는 다른 안정화제(stabilizers)들을 더 포함할 수 있다.The graphene oxide nanocomposite for diagnosis or treatment of cancer cells according to the present invention may be injected into a blood vessel through an injection at the time of clinical administration, and the injection composition is ethyl oleate in addition to the graphene oxide nanocomposite for diagnosis or treatment of cancer cells according to the present invention. Injectable esters, such as physiological saline, and the like, and carbohydrates such as glucose, sucrose or dextran, antioxidants such as ascorbic acid or glutathione, chelating to increase stability It may further comprise chelating agents, low molecular weight proteins or other stabilizers.
상기 주사제 조성물에서 암세포 진단용 또는 치료용 그래핀 옥사이드 나노복합체의 유효함량은 바람직하게는 1 내지 50%이고, 암 진단 또는 치료시에 상기 유효함량으로 포함된 주사제가 1 ~ 100 ml 투여될 수 있다.The effective amount of the graphene oxide nanocomposite for diagnosing or treating cancer cells in the injection composition is preferably 1 to 50%, and an injection containing 1 to 100 ml may be administered in the effective amount at the time of diagnosing or treating cancer.
한편, 본 발명에 따른 암세포 치료용 그래핀 옥사이드 나노복합체를 유효성분으로 함유하는 주사제는 단일 투여량(single dose)으로 피투여체에게 투여될 수 있으며, 5 ~ 24시간 간격을 두고 다중 투여량(multiple dose)으로 분할 투여될 수 있다.On the other hand, injections containing a graphene oxide nanocomposite for cancer cell treatment according to the present invention as an active ingredient may be administered to the subject in a single dose, multiple doses at intervals of 5 to 24 hours in divided doses).
다만, 본 발명에 따른 암세포 치료용 그래핀 옥사이드 나노복합체를 유효성분으로 함유하는 주사제는 피투여체의 나이 및 건강상태 등 다양한 요인들을 고려하여 유효 투여량이 결정되는 것이므로, 이러한 점을 고려할 때 이 분야의 통상적인 지식을 가진 자라면 적절한 유효 투여량을 결정할 수 있다.However, since the injection dose containing the graphene oxide nanocomposite as an active ingredient for treating cancer cells according to the present invention is determined in consideration of various factors such as age and health condition of the administered subject, an effective dose is determined in this field. One of ordinary skill can determine the appropriate effective dosage.
상기와 같이 주사제가 투여된지 1 ~ 24 시간 후 통상적인 방법에 의해 혈액을 투석하고, 투석 시 투석기에 자기장의 세기가 0.1 ~ 10 Tesla인 자기장을 지속적으로 형성시켜 암세포 치료용 그래핀 옥사이드 나노복합체와 결합된 암세포를 클로닝할 수 있으며, 클로닝된 암세포에 파장이 700 ~ 1000nm인 레이저를 조사함으로써 암세포를 파괴시켜 혈액속에 존재하는 전이암을 제거할 수 있다.1 to 24 hours after the injection is administered as described above, the dialysis of the blood by a conventional method, and during dialysis, by continuously forming a magnetic field of 0.1 to 10 Tesla magnetic field strength on the dialysis and cancer cell therapy graphene oxide nanocomposites The combined cancer cells can be cloned and the cancer cells can be destroyed by irradiating the cloned cancer cells with a laser having a wavelength of 700 to 1000 nm to remove metastatic cancer present in the blood.
하기의 실시예를 통하여 본 발명을 더욱 구체적으로 설명하기로 하지만, 하기 실시예가 본 발명의 범위를 제한하는 것은 아니며, 이는 본 발명의 이해를 돕기 위한 것으로 해석되어야 할 것이다.Although the present invention will be described in more detail with reference to the following examples, the following examples are not intended to limit the scope of the present invention, which will be construed as to aid the understanding of the present invention.
<준비예 1> - 그래핀 옥사이드 나노시트의 제조Preparation Example 1 Preparation of Graphene Oxide Nanosheets
그래파이트 플래이크(Duksan, cat#798) 100 중량부에 대해 5,000~20,000 중량부의 90% 이상의 황산수용액 및 85% 인산수용액 혼합용액(혼합비율 농축황산수용액과 인산수용액이 9 : 1 부피비)을 혼합한 후, 35℃에서 2시간 천천히 교반하면서 과망간산칼륨을 그래핀 플래이크 100 중량부에 대해 500중량부 투입했다. 이후 혼합용액을 3 ~ 4℃로 냉각시킨 후 30중량% 과산화수소 수용액이 1ml 첨가된 증류수 300mL를 투입하여 7℃에서 300rpm으로 교반하면서 과량의 과망간산칼륨을 제거하였다. 형성된 고형물의 분리를 위해 이후 기공공경이 약 450nm인 셀룰로오스 아세테이트 막을 사용하여 고형물을 분리하였고, 분리된 고형물을 증류수를 이용하여 정제, 세척한 후, 10 중량% 염산수용액을 몇 방울 떨어뜨려 15000 rpm으로 30분간 원심분리하고 최종 제조물을 12시간 진공건조시켜 단층의 그래파이트 옥사이드 나노시트를 제조하였다. 100 parts by weight of graphite plaque (Duksan, cat # 798) containing 5,000 to 20,000 parts by weight of 90% or more sulfuric acid solution and 85% phosphoric acid solution mixed solution (mixed ratio concentrated sulfuric acid solution and phosphate solution in a 9: 1 volume ratio) Thereafter, 500 parts by weight of potassium permanganate was added to 100 parts by weight of the graphene plaque while stirring slowly at 35 ° C for 2 hours. Then, after cooling the mixed solution to 3 ~ 4 ℃ 300ml distilled water to which 30% by weight aqueous hydrogen peroxide solution 1ml was added and stirred at 300rpm at 7 ℃ to remove excess potassium permanganate. For the separation of the formed solids, the solids were then separated using a cellulose acetate membrane having a pore diameter of about 450 nm, and the separated solids were purified and washed with distilled water, followed by several drops of 10 wt% aqueous hydrochloric acid solution at 15000 rpm. Centrifugation was carried out for 30 minutes and the final product was vacuum dried for 12 hours to prepare a single layer of graphite oxide nanosheets.
<준비예 2> - 아민기로 표면개질된 제1 나노입자의 제조Preparation Example 2 Preparation of First Nanoparticles Surface-Modified with Amine Group
올레산으로 코팅된 직경이 13±2.5nm인 사산화삼철(Fe3O4)(OceanNanotechLLC사 상품명 : SOR) 300㎕를 사이클로헥산(Sigma-Aldrich) 29.2ml에 혼합하여 분산시킨 후, Triton-X100 (Sigma-Aldrich) 560㎕, 29.3중량% 암모니아수(Sigma-Aldrich) 22.4㎕를 첨가하였다. 이후 상기 혼합용액에 40mM 1-옥탄올을 투입하되, 상기 혼합용액이 투명해질 때까지 첨가하였다. 이후 165mM의 테트라에틸오르쏘실리케이트(TEOS, Sigma Aldrich)를 100 ml투입하고 72시간 동안 상온에서 600rpm으로 교반하여 실리카 쉘층을 성장시켰다. 이후 아세톤을 5 ml 투입하여 반응을 종결시켰으며, 15,000 rpm으로 30분간 원심분리시켜 과량의 유기용매를 제거하여 제1 나노입자를 제조하였다.300 μl of triiron tetraoxide (Fe 3 O 4 ) (Ocean Nanotech LLC company name: SOR) coated with oleic acid was dispersed in 29.2 ml of cyclohexane (Sigma-Aldrich), and then dispersed in Triton-X100 (Sigma). 560 µl of Aldrich and 22.4 µl of 29.3 wt. Thereafter, 40 mM 1-octanol was added to the mixed solution, and the mixed solution was added until it became clear. Thereafter, 100 ml of 165 mM tetraethylorthosilicate (TEOS, Sigma Aldrich) was added and stirred at 600 rpm at room temperature for 72 hours to grow a silica shell layer. Thereafter, 5 ml of acetone was added to terminate the reaction, and the first nanoparticle was prepared by removing the excess organic solvent by centrifugation at 15,000 rpm for 30 minutes.
상기 제1 나노입자를 아민기로 표면개질 시키기 위해 제1 나노입자를 분산용매인 99.9중량% 에탄올에 투입하고, 3-아미노프로필트리에톡시실란(APTS, Sigma-Aldrich)을 제1 나노입자 100 중량부에 대해 10 중량부 투입하여 상온에서 6시간 동안 교반하였다. 이후 제조된 나노입자를 증류수에 세척과정을 거쳐 표면개질된 제1 나노입자를 제조하였다.In order to surface-modify the first nanoparticles into an amine group, the first nanoparticles were added to 99.9% by weight of ethanol as a dispersion solvent, and 3-aminopropyltriethoxysilane (APTS, Sigma-Aldrich) was loaded with 100 parts of the first nanoparticles. 10 parts by weight of the parts were added and stirred at room temperature for 6 hours. Thereafter, the prepared nanoparticles were washed in distilled water to prepare surface-modified first nanoparticles.
<준비예 3> - 실란기로 표면개질된 제2 나노입자 제조Preparation Example 3 Preparation of Second Nanoparticles Surface-Modified with Silane Group
광열 금속물질로 금나노로드를 이용하기 위해, Murphy에 의해 연구된 씨드-매개된 금나노로드 제조방법을 이용하였다. In order to use gold nanorods as photothermal metal materials, a seed-mediated gold nanorod manufacturing method studied by Murphy was used.
먼저, 씨드 용액을 제조하기 위해 0.2M CTAB(hexadecylcetyltrimethylammonium bromide) 수용액 2ml에 0.5mM HAuCl4·4H2O(hydrogentetrachloroaurate(III)tetrahydrate)를 5ml 혼합한 후 냉각된(ice-cold) 0.01 M의 NaBH4를 첨가해 2분 동안 볼텍싱 하였다. 그 결과 씨드 솔루션이 황갈색으로 변하였다.First, 5 ml of 0.5 mM HAuCl 4 · 4H 2 O (hydrogentetrachloroaurate (III) tetrahydrate) was mixed with 2 ml of 0.2 M CTAB (hexadecylcetyltrimethylammonium bromide) solution to prepare a seed solution, followed by ice-cold 0.01 M NaBH 4 Was added and vortexed for 2 minutes. As a result, the seed solution turned tan.
한편, 금나노로드 성장용액을 제조하기 위해 1mM의 HAuCl4·4H2O(hydrogentetrachloroaurate(III)tetrahydrate)50ml를 0.2M CTAB 수용액 50ml과 혼합시켰고, 그 다음에 4mM 질산은 수용액 1.2ml와 7.9mM의 아스코빅산 수용액 0.7ml를 마그네틱 스티어링하여 혼합하였다. Meanwhile, to prepare a gold nanorod growth solution, 50 ml of 1 mM of HAuCl 4 · 4H 2 O (hydrogentetrachloroaurate (III) tetrahydrate) was mixed with 50 ml of 0.2 M CTAB aqueous solution, and then 4 mM ammonium nitrate was dissolved in 1.2 ml of aqueous solution and 7.9 mM ascorbic acid. 0.7 ml of an aqueous bixane solution was mixed by magnetic steering.
상기 제조된 씨드용액은 이를 사용하기 전 상온에서 30분 동안 에이징시켰고, 이후 60㎕의 씨드용액을 성장용액 100 ml에 교반하면서 투입하였다. 이후 용액의 색상이 어두운 적색으로 변할 때까지 교반을 계속하다가 색상이 변화한 후 여부의 CTAB 용액을 제거하기 위해 증류수로 2번 최종 제조물을 세척하여 종횡비(aspect ratio)가 4인 금나노로드를 제조하였다.The prepared seed solution was aged at room temperature for 30 minutes before use, and then 60 µl of the seed solution was added to 100 ml of the growth solution with stirring. Then, stirring was continued until the color of the solution turned dark red, and then the final product was washed twice with distilled water to remove the CTAB solution after the color was changed to prepare a gold nanorod having an aspect ratio of 4. It was.
상기 제조된 금 나노로드를 약0.01g의 mPEG-SH (MW 1,000, Laysan Bio)에 투입하여 폴리에틸렌글리콜화 시켰으며, 이후 99.9 중량%의 에탄올에 제조된 폴리에틸렌글리콜화된 금 나노로드를 분산시켰다.The prepared gold nanorods were added to about 0.01 g of mPEG-SH (MW 1,000, Laysan Bio) for polyethylene glycolation, and then the polyethylene glycolated gold nanorods were dispersed in 99.9 wt% ethanol.
상기 분산된 금 나노로드가 포함된 용액에 MPTS(3-mercaptopropyltrimethoxysilane, Sigma-Aldrich)를 금 나노로드 100 중량부에 대해 10 중량부 투입하여 3시간동안 상온에서 교반시켜 폴리에틸렌글리콜화된 금 나노로드 표면을 실란기로 개질시킨 제2 나노입자를 제조하였다. 10 parts by weight of MPTS (3-mercaptopropyltrimethoxysilane, Sigma-Aldrich) was added to 100 parts by weight of the gold nanorods in the solution containing the dispersed gold nanorods, and stirred at room temperature for 3 hours to give a polyethylene glycolated gold nanorod surface. To prepare a second nanoparticles modified with a silane group.
<실시예 1> <Example 1>
준비예 1을 통해 제조된 두께가 1.2 nm인 그래핀 옥사이드 나노시트 100 중량부에 대해 준비예 2를 통해 제조된 제1 나노입자를 20 중량부, 커플링제로 EDC(Thermo Scientific) 20 중량부, 커플링 보조제로 NHS(Thermo Scientific)를 20 중량부 혼합시켜 상온에서 3 시간 동안 교반한 후 원심분리기를 이용해 증류수로 세척하여 제1 복합체를 제조하였다. 이후 충분한 양의 분산용매 에탄올에 상기 제1 복합체 100 중량부에 대해 준비예 3을 통해 제조된 제2 나노입자를 20 중량부 투입하여 상온에서 3 시간 동안 교반하여 제2 복합체를 제조하였고, 상등액을 제거한 후 그래핀 옥사이드 나노복합체를 제조하였다.20 parts by weight of the first nanoparticles prepared through Preparation Example 2, 20 parts by weight of EDC (Thermo Scientific) as a coupling agent, based on 100 parts by weight of graphene oxide nanosheets having a thickness of 1.2 nm prepared in Preparation Example 1, NHS (Thermo Scientific) was mixed with a coupling aid 20 parts by weight, stirred at room temperature for 3 hours, and then washed with distilled water using a centrifuge to prepare a first complex. Thereafter, 20 parts by weight of the second nanoparticles prepared according to Preparation Example 3 was added to 100 parts by weight of the first solvent in a sufficient amount of the dispersion solvent, stirred at room temperature for 3 hours to prepare a second composite, and the supernatant was After removal, a graphene oxide nanocomposite was prepared.
<비교예 1>Comparative Example 1
실시예 1과 동일하게 실시하여 제조하되, 준비예 3을 통해 제조된 제2 나노입자를 투입하지 않고 그래핀 옥사이드 나노복합체를 제조하였다.Prepared in the same manner as in Example 1, but did not add the second nanoparticles prepared in Preparation Example 3 to prepare a graphene oxide nanocomposite.
<실험예 1>Experimental Example 1
준비예 1 내지 3, 비교예 1 및 실시예 1에 의한 제조물에 대해 투과전자현미경 사진을 촬영하여 각각 도 5 내지 9에 나타내었다.Transmission electron micrographs of the preparations according to Preparation Examples 1 to 3, Comparative Example 1 and Example 1 were taken and shown in FIGS. 5 to 9, respectively.
구체적으로 도 6에서 도 6(b)는 도 6(a)의 사산화삼철이 코어부로 포함되고 실리카가 상기 코어부를 감싸는 구조인 코어쉘 구조의 제1 나노입자가 제조되었음을 확인할 수 있다.Specifically, in FIG. 6 (b) it can be seen that the first nanoparticles of the core shell structure is a structure in which the triiron tetraoxide of Figure 6 (a) is included as a core portion and silica surrounds the core portion.
또한, 도 8을 통해 도 5의 그래핀 옥사이드와 및 도 6의 제1 나노입자를 포함하는 복합체가 제조되었음을 확인할 수 있다.In addition, it can be seen through FIG. 8 that the composite including the graphene oxide of FIG. 5 and the first nanoparticles of FIG. 6 was prepared.
나아가, 도 9를 통해 도 8의 복합체와 도 7의 제2 나노입자를 포함하는 복합체가 제조되었음을 알 수 있다.Furthermore, it can be seen from FIG. 9 that the composite including the composite of FIG. 8 and the second nanoparticle of FIG. 7 was prepared.
<실험예 2>Experimental Example 2
준비예 1(a), 비교예 1(b), 준비예 3(c) 및 실시예 1(d)에 대해 자외선-가시광선 흡광도 스펙트럼(UV-Vis absorption spectrum)을 측정하여 도 10에 나타내었다.UV-Vis absorption spectrum was measured for Preparation Example 1 (a), Comparative Example 1 (b), Preparation Example 3 (c), and Example 1 (d) and shown in FIG. 10. .
구체적으로 도 10에서 실시예 1(d) 스펙트럼의 경우 약 250nm에서의 준비예1(a)인 그래핀 옥사이드의 흡광 피크와 약 800nm에서의 준비예3(c)인 제2 나노입자의 흡광 피크를 모두 나타냄으로써 실시예 1(d)의 나노복합체는 그래핀 옥사이드, 제2 나노입자를 포함하고 있음을 확인할 수 있다. Specifically, in Example 1 (d) spectrum, in FIG. 10, an absorption peak of graphene oxide as Preparation Example 1 (a) at about 250 nm and an absorption peak of second nanoparticles as Preparation Example 3 (c) at about 800 nm are shown. By showing all of the nanocomposite of Example 1 (d) it can be seen that the graphene oxide, including the second nanoparticles.
<실험예 3>Experimental Example 3
광열효과를 평가하기 위해서, 준비예 1의 그래핀 옥사이드, 비교예 1의 제1 나노입자/그래핀옥사이드 복합체, 준비예 3의 제2 나노입자 및 실시예 1의 제2 나노입자/제1 나노입자/그래핀옥사이드 복합체를 증류수 100 중량부에 대해 10 중량부 투입한 후 파장 780nm, 세기 2mW/㎠의 근적외선레이저를 조사하여 시간당 온도를 측정하여 도 11에 나타내었다. 이때, 대조군으로 증류수를 사용하였다.In order to evaluate the photothermal effect, the graphene oxide of Preparation Example 1, the first nanoparticles / graphene oxide composite of Comparative Example 1, the second nanoparticles of Preparation Example 3 and the second nanoparticles / first nano of Example 1 10 parts by weight of the particle / graphene oxide composite was added to 100 parts by weight of distilled water, and then irradiated with a near infrared laser having a wavelength of 780 nm and an intensity of 2 mW / cm 2. At this time, distilled water was used as a control.
구체적으로 도 11에서 그래핀 옥사이드 및 제1 나노입자/그래핀 옥사이드 복합체의 경우 시간당 온도증가가 비슷한 것을 확인할 수 있고, 이를 통해 제1 나노입자는 광열효과에는 영향을 미치지 않는다는 것을 알 수 있으며 증류수와 대비하여 레이저 조사 시간에 따른 온도증가를 보임에 따라 그래핀 옥사이드 자체도 광열효과를 발현함을 알 수 있다.Specifically, in the case of graphene oxide and the first nanoparticles / graphene oxide composite in Figure 11 it can be seen that the temperature increase per hour is similar, through which it can be seen that the first nanoparticles do not affect the photothermal effect and with distilled water In contrast, as the temperature increases with laser irradiation time, it can be seen that graphene oxide itself exhibits a photothermal effect.
또한, 제2 나노입자의 경우에 비해 본 발명에 따른 제2 나노입자/제1 나노입자/그래핀옥사이드 복합체가 광열효과가 현저히 우수함을 확인할 수 있고, 레이저 조사 시간별 증가된 온도에서 본 발명에 따른 제2 나노입자/제1 나노입자/그래핀옥사이드 복합체 증가온도가 제2 나노입자의 증가온도 및 그래핀옥사이드 증가온도 에 비해 더 큰 것을 통해 그래핀 옥사이드와 제2 나노입자가 광열효과에 있어 상승효과를 발현함을 확인할 수 있다. 이러한 상승효과는 레이져 조사 시간일 길수록 더욱 현저함을 확인할 수 있다.In addition, it can be seen that the second nanoparticles / first nanoparticles / graphene oxide composite according to the present invention have a remarkably excellent light-heating effect compared to the case of the second nanoparticles, and according to the present invention at an increased temperature for each laser irradiation time. The graphene oxide and the second nanoparticles are increased in the photothermal effect through the increase in the temperature of the second nanoparticle / first nanoparticle / graphene oxide composite is greater than the increase temperature and the graphene oxide increase temperature of the second nanoparticle. It can be confirmed that the effect is expressed. This synergistic effect can be confirmed that the longer the laser irradiation time is more remarkable.

Claims (14)

  1. 그래핀 옥사이드(GO) 나노시트를 포함하는 지지체;A support comprising graphene oxide (GO) nanosheets;
    상기 그래핀 옥사이드 나노시트상에 공유결합되어 포함되며, 자성을 띠는 제1 나노입자; 및It is included covalently bonded on the graphene oxide nanosheets, the first nanoparticles having a magnetic; And
    상기 그래핀옥사이드(GO) 및 제1 나노입자 중 적어도 하나 이상에 공유결합되어 포함되며, 광열효과를 발현하는 제2 나노입자;를 포함하는 광열효과가 우수한 그래핀 옥사이드 나노복합체.The graphene oxide nanocomposite having excellent photothermal effects, including; and covalently bonded to at least one or more of the graphene oxide (GO) and the first nanoparticles, the second nanoparticles expressing the photothermal effect.
  2. 제1항에 있어서,The method of claim 1,
    상기 나노시트는 단층의 그래핀 옥사이드인 것을 특징으로 하는 광열효과가 우수한 그래핀 옥사이드 나노복합체.The nanosheets are excellent graphene oxide nanocomposite, characterized in that the graphene oxide of a single layer.
  3. 제1항에 있어서, 상기 제1 나노입자는The method of claim 1, wherein the first nanoparticles
    자성물질을 포함하는 코어층; 및A core layer comprising a magnetic material; And
    상기 코어층을 둘러싸고, 싸이올기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기를 포함하여 표면 개질된 실리카 쉘층;을 포함하는 것을 특징으로 하는 광열효과가 우수한 그래핀 옥사이드 나노복합체. A graphene oxide nanocomposite having excellent photothermal effects, comprising: surrounding the core layer, a surface-modified silica shell layer including any one or more functional groups selected from the group consisting of a thiol group, an amine group, and a carboxyl group.
  4. 제3항에 있어서,The method of claim 3,
    상기 자성물질은 코발트(Co), 망간(Mn), 철(Fe), 니켈(Ni), 가돌리늄(Gd), 게르마늄(Ge), 몰리브덴(Mo), MM’2O4및 MxOy로 이루어진 군에서 선택된 어느 하나 이상의 금속물질; 및 코발트-구리(CoCu), 코발트-백금(CoPt), 철-백금(FePt), 코발트-사마륨(CoSm), 니켈-철(NiFe) 및 니켈-철-코발트(NiFeCo)로 이루어진 군에서 선택된 어느 하나 이상의 금속합금;중 어느 하나 이상을 포함하는 것을 특징으로 하는 광열효과가 우수한 그래핀 옥사이드 나노복합체.The magnetic material is cobalt (Co), manganese (Mn), iron (Fe), nickel (Ni), gadolinium (Gd), germanium (Ge), molybdenum (Mo), MM ' 2 O 4 and M x O y Any one or more metal materials selected from the group consisting of; And cobalt-copper (CoCu), cobalt-platinum (CoPt), iron-platinum (FePt), cobalt-samarium (CoSm), nickel-iron (NiFe), and nickel-iron-cobalt (NiFeCo). Graphene oxide nanocomposite having excellent thermal effects, characterized in that it comprises one or more of at least one metal alloy.
    이때, 상기 M또는 M’은 Co, Mn, Fe, Ni, Gd, Ge, Mo 이며, 0<x≤3, 0<y≤5임.In this case, M or M 'is Co, Mn, Fe, Ni, Gd, Ge, Mo, 0 <x ≤ 3, 0 <y ≤ 5.
  5. 제1항에 있어서, The method of claim 1,
    상기 제2 나노입자는 실란기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기를 포함하여 표면개질된 광열 금속 나노입자인 것을 특징으로 하는 광열효과가 우수한 그래핀 옥사이드 나노복합체.The second nanoparticle is a graphene oxide nanocomposite having excellent photothermal effects, characterized in that the surface-modified photothermal metal nanoparticles including any one or more functional groups selected from the group consisting of a silane group, an amine group and a carboxyl group.
  6. 제1항에 있어서,The method of claim 1,
    상기 제2 나노입자 형상은 로드(rod)형인 것을 특징으로 하는 광열효과가 우수한 그래핀 옥사이드 나노복합체.The second nanoparticle shape is a rod (rod) type excellent graphene oxide nanocomposite, characterized in that the thermal effect.
  7. 제5항에 있어서,The method of claim 5,
    상기 광열 금속 나노입자는 금, 은, 팔라듐, 백금, 구리 및 알루미늄 이루어진 군에서 선택된 어느 하나 이상을 포함하는 것을 특징으로 하는 광열효과가 우수한 그래핀 옥사이드 나노복합체. The photothermal metal nanoparticles are excellent graphene oxide nanocomposites, characterized in that it comprises any one or more selected from the group consisting of gold, silver, palladium, platinum, copper and aluminum.
  8. 제1항에 있어서, 상기 나노복합체는 The method of claim 1, wherein the nanocomposite
    단층의 그래핀 옥사이드 나노시트를 포함하는 지지체;A support comprising a single layer of graphene oxide nanosheets;
    사산화삼철(Fe3O4)을 포함하는 자성물질을 포함하는 코어층 및 상기 코어층을 둘러싸고 아민기로 표면개질된 실리카 쉘층을 포함하고 상기 그래핀 옥사이드 나노시트상에 공유결합하여 포함되는 제1 나노입자; 및 A first nano-containing core layer comprising a magnetic material containing triiron tetraoxide (Fe 3 O 4 ) and a silica shell layer surrounding the core layer and surface-modified with an amine group and covalently included on the graphene oxide nanosheets. particle; And
    표면이 실란기로 개질된 종횡비(aspect ratio)가 3 ~ 4인 금나노로드를 포함하는 광열금속입자를 포함하고, 상기 그래핀 옥사이드 나노시트 및 제1 나노입자 중 어느 하나 이상과 공유결합하여 포함되는 제2 나노입자;를 포함하는 것을 특징으로 하는 광열효과가 우수한 그래핀 옥사이드 나노복합체.It includes a photothermal metal particles including a gold nanorod having an aspect ratio of 3 to 4 modified surface of the silane group, and is covalently included with any one or more of the graphene oxide nanosheets and the first nanoparticles Graphene oxide nanocomposite having excellent photothermal effects, characterized in that it comprises a second nanoparticle.
  9. 제8항에 있어서, The method of claim 8,
    상기 나노복합체는 파장이 780nm이고, 세기가 2mW/cm2인 레이저를 조사시 하기의 조건 (1) 내지 (3)을 만족하는 것을 특징으로 하는 광열효과가 우수한 그래핀 옥사이드 나노복합체.The nanocomposite is a graphene oxide nanocomposite having excellent light-heating effect, characterized in that to satisfy the following conditions (1) to (3) when irradiating a laser of wavelength 780nm, 2mW / cm 2 intensity.
    (1) 레이저 조사 100초 경과 후 증가된 온도가 레이저 조사 전에 비해 6℃ 이상임.(1) The temperature increased after 100 seconds of laser irradiation is 6 ° C. or more than before laser irradiation.
    (2) 레이저 조사 300초 경과 후 증가된 온도가 레이저 조사 전에 비해 20℃ 이상임.(2) The temperature increased after 300 seconds of laser irradiation is 20 ° C. or more than before laser irradiation.
    (3) 레이져 조사 900 초 경과 후 증가된 온도가 레이저 조사 전에 비해 38℃ 이상임.(3) After 900 seconds of laser irradiation, the increased temperature is more than 38 ℃ compared to before laser irradiation.
  10. (1) 자성을 띠는 제1 나노입자를 포함하는 용액에 그래핀 옥사이드 나노시트를 투입하여 제1 복합체를 제조하는 단계; 및(1) preparing a first composite by injecting graphene oxide nanosheets into a solution containing magnetic first nanoparticles; And
    (2) 상기 제1 복합체를 광열효과를 발현하는 제2 나노입자가 포함된 용액에 투입하여 제2 복합체를 제조하는 단계;를 포함하는 광열효과가 우수한 그래핀 옥사이드 나노복합체 제조방법.(2) preparing the second composite by adding the first composite into a solution containing the second nanoparticles expressing the photothermal effect; and a graphene oxide nanocomposite having excellent photothermal effects.
  11. 제10항에 있어서,The method of claim 10,
    상기 (1) 단계는 제1 나노입자의 실리카 쉘층 표면에 포함된 싸이올기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기와 그래핀 옥사이드 나노시트에 포함된 싸이올기, 히드록시기 및 카르복시기로 이루어진 군에서 선택된 어느 하나 이상의 작용기 간에 공유결합을 형성시키는 것을 특징으로 하는 광열효과가 우수한 그래핀 옥사이드 나노복합체 제조방법.Step (1) comprises at least one functional group selected from the group consisting of a thiol group, an amine group, and a carboxyl group included on the surface of the silica shell layer of the first nanoparticle, and a thiol group, a hydroxyl group, and a carboxyl group included in the graphene oxide nanosheets. Graphene oxide nanocomposite manufacturing method excellent in the photothermal effect, characterized in that to form a covalent bond between any one or more functional groups selected from the group.
  12. 제10항에 있어서,The method of claim 10,
    상기 (2) 단계는 제1 복합체에 포함된 제1 나노입자의 실리카 쉘층에 포함된 싸이올기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기; 및 그래핀 옥사이드 나노시트에 포함된 싸이올기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기; 중 어느 하나 이상의 작용기와 광열 금속 나노입자 표면의 실란기, 아민기 및 카르복실기로 이루어진 군에서 선택된 어느 하나 이상의 작용기 간에 공유결합을 형성시키는 것을 특징으로 하는 광열효과가 우수한 그래핀 옥사이드 나노복합체 제조방법.Step (2) is at least one functional group selected from the group consisting of a thiol group, an amine group and a carboxyl group included in the silica shell layer of the first nanoparticles included in the first composite; And one or more functional groups selected from the group consisting of a thiol group, an amine group, and a carboxyl group included in the graphene oxide nanosheets; Method for producing a graphene oxide nanocomposite having excellent light-heating effect, characterized in that to form a covalent bond between any one or more of the functional group and any one or more functional groups selected from the group consisting of silane groups, amine groups and carboxyl groups on the surface of the photothermal metal nanoparticles.
  13. 제1항에 따른 나노복합체를 포함하는 암세포 진단용 그래핀 옥사이드 나노복합체.Graphene oxide nanocomposite for cancer cell diagnosis comprising the nanocomposite according to claim 1.
  14. 제1항에 따른 나노복합체를 포함하는 암세포 치료용 그래핀 옥사이드 나노복합체.Graphene oxide nanocomposites for treating cancer cells comprising the nanocomposites according to claim 1.
PCT/KR2014/002350 2014-03-19 2014-03-20 Graphene oxide nanocomposite exhibiting excellent photothermal effect and manufacturing method therefor WO2015141876A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2014-0032384 2014-03-19
KR1020140032384A KR101516116B1 (en) 2014-03-19 2014-03-19 Graphen oxide nano-composite having excellent photothermal effect and method for manufacturing thereof

Publications (1)

Publication Number Publication Date
WO2015141876A1 true WO2015141876A1 (en) 2015-09-24

Family

ID=53393383

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2014/002350 WO2015141876A1 (en) 2014-03-19 2014-03-20 Graphene oxide nanocomposite exhibiting excellent photothermal effect and manufacturing method therefor

Country Status (2)

Country Link
KR (1) KR101516116B1 (en)
WO (1) WO2015141876A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114931947A (en) * 2022-05-31 2022-08-23 武汉理工大学 Novel way for light-to-heat driving unsaturated alkene alkyne selective catalytic hydrogenation and catalyst thereof
CN115354380A (en) * 2022-08-25 2022-11-18 安徽工业大学 Method for constructing solid super-smooth surface
CN115491263A (en) * 2022-10-24 2022-12-20 中国人民解放军军事科学院防化研究院 Preparation and use methods of modified nano graphene oxide stability-enhancing synergistic anti-freezing foam detergent

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101945112B1 (en) 2017-07-31 2019-02-01 금오공과대학교 산학협력단 Patch composition comprising graphene oxide gold nanoroad
KR101964944B1 (en) * 2017-08-03 2019-04-03 한국과학기술연구원 Analysis of graphene derivatives
KR102136001B1 (en) 2018-01-10 2020-07-21 금오공과대학교 산학협력단 Patch composition comprising dog bone gold nano rod, graphene oxide or charcoal
KR102189350B1 (en) * 2018-11-30 2020-12-09 연세대학교 원주산학협력단 Transparent electrode based on the silver nanowires and manufacturing method thereof
CN115430427B (en) * 2022-09-05 2023-07-07 安庆市长三角未来产业研究院 Photo-thermal synergistic catalyst for efficiently degrading low-concentration VOCs, and preparation method and application thereof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20120017408A (en) * 2010-08-18 2012-02-28 한국생명공학연구원 The method of catalyst activation using photothermal nanomaterials
US20120220053A1 (en) * 2011-02-17 2012-08-30 Rutgers, The State University Of New Jersey Graphene-encapsulated nanoparticle-based biosensor for the selective detection of biomarkers
KR20130140356A (en) * 2012-06-14 2013-12-24 전자부품연구원 Hybrid composite of graphene oxide and quantum dot
KR20140014443A (en) * 2012-07-24 2014-02-06 국립암센터 Graphene oxide-photosensitizers complex containing disulfide linker and composition for diagonosis and therapy of canncer using the same
US20140072879A1 (en) * 2012-09-10 2014-03-13 Guorong Chen Encapsulated phthalocyanine particles, high-capacity cathode containing these particles, and rechargeable lithium cell containing such a cathode

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20120017408A (en) * 2010-08-18 2012-02-28 한국생명공학연구원 The method of catalyst activation using photothermal nanomaterials
US20120220053A1 (en) * 2011-02-17 2012-08-30 Rutgers, The State University Of New Jersey Graphene-encapsulated nanoparticle-based biosensor for the selective detection of biomarkers
KR20130140356A (en) * 2012-06-14 2013-12-24 전자부품연구원 Hybrid composite of graphene oxide and quantum dot
KR20140014443A (en) * 2012-07-24 2014-02-06 국립암센터 Graphene oxide-photosensitizers complex containing disulfide linker and composition for diagonosis and therapy of canncer using the same
US20140072879A1 (en) * 2012-09-10 2014-03-13 Guorong Chen Encapsulated phthalocyanine particles, high-capacity cathode containing these particles, and rechargeable lithium cell containing such a cathode

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114931947A (en) * 2022-05-31 2022-08-23 武汉理工大学 Novel way for light-to-heat driving unsaturated alkene alkyne selective catalytic hydrogenation and catalyst thereof
CN115354380A (en) * 2022-08-25 2022-11-18 安徽工业大学 Method for constructing solid super-smooth surface
CN115491263A (en) * 2022-10-24 2022-12-20 中国人民解放军军事科学院防化研究院 Preparation and use methods of modified nano graphene oxide stability-enhancing synergistic anti-freezing foam detergent
CN115491263B (en) * 2022-10-24 2024-03-12 中国人民解放军军事科学院防化研究院 Preparation and application methods of modified nano graphene oxide stability-enhancing and efficiency-enhancing antifreezing foam detergent

Also Published As

Publication number Publication date
KR101516116B1 (en) 2015-05-06

Similar Documents

Publication Publication Date Title
WO2015141876A1 (en) Graphene oxide nanocomposite exhibiting excellent photothermal effect and manufacturing method therefor
Kumar et al. Evaluating the toxicity of selected types of nanochemicals
Yang et al. Nano-black phosphorus for combined cancer phototherapy: recent advances and prospects
Alegret et al. Recent advances of graphene-based hybrids with magnetic nanoparticles for biomedical applications
Kadian et al. Recent advancements in synthesis and property control of graphene quantum dots for biomedical and optoelectronic applications
CN105969331B (en) A kind of preparation method of nano material suitable for target medicine carrier
Lan et al. Nanoparticles and spermatogenesis: how do nanoparticles affect spermatogenesis and penetrate the blood–testis barrier
Kumar et al. Advanced metal and carbon nanostructures for medical, drug delivery and bio-imaging applications
Singh et al. Nanotechnology and health safety–toxicity and risk assessments of nanostructured materials on human health
Rzigalinski et al. Radical nanomedicine
Liu et al. Superparamagnetic nanosystems based on iron oxide nanoparticles for biomedical imaging
Attia et al. Nanodiamond–polymer nanoparticle composites and their thin films
Xiao et al. Advances and challenges of fluorescent nanomaterials for synthesis and biomedical applications
Lacroix et al. New generation of magnetic and luminescent nanoparticles for in vivo real-time imaging
KR101317456B1 (en) Magnetite-Ag Core-shell nanoparticle and Method for Preparing the Same
Pati et al. Magnetic chitosan-functionalized Fe3O4@ Au nanoparticles: Synthesis and characterization
Shtansky et al. Recent progress in fabrication and application of BN nanostructures and BN-based nanohybrids
Turcheniuk et al. Insulin loaded iron magnetic nanoparticle–graphene oxide composites: synthesis, characterization and application for in vivo delivery of insulin
Zhang et al. Self‐assembly multifunctional nanocomposites with Fe3O4 magnetic core and CdSe/ZnS quantum dots shell
Kargbo et al. Recent advances in luminescent carbon dots
Wang et al. An efficient strategy to synthesize a multifunctional ferroferric oxide core@ dye/SiO 2@ Au shell nanocomposite and its targeted tumor theranostics
Behnam et al. PEGylated carbon nanotubes decorated with silver nanoparticles: fabrication, cell cytotoxicity and application in photo thermal therapy
Zhou et al. Plasmonic oxygen defects in MO3− x (M= W or Mo) nanomaterials: synthesis, modifications, and biomedical applications
Veintemillas-Verdaguer et al. Continuous production of inorganic magnetic nanocomposites for biomedical applications by laser pyrolysis
al din Haratifar et al. Semi-biosynthesis of magnetite-gold composite nanoparticles using an ethanol extract of Eucalyptus camaldulensis and study of the surface chemistry

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14885958

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 14885958

Country of ref document: EP

Kind code of ref document: A1