WO2014109459A1 - Procédé de préparation de nanoparticules d'or utilisant des micelles comme moule - Google Patents

Procédé de préparation de nanoparticules d'or utilisant des micelles comme moule Download PDF

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WO2014109459A1
WO2014109459A1 PCT/KR2013/009152 KR2013009152W WO2014109459A1 WO 2014109459 A1 WO2014109459 A1 WO 2014109459A1 KR 2013009152 W KR2013009152 W KR 2013009152W WO 2014109459 A1 WO2014109459 A1 WO 2014109459A1
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gold nanoparticles
acid
tocopherol
micelles
copolymer
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Korean (ko)
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정지훈
이민상
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성균관대학교산학협력단
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F9/00—Making metallic powder or suspensions thereof
    • B22F9/16—Making metallic powder or suspensions thereof using chemical processes
    • B22F9/18—Making metallic powder or suspensions thereof using chemical processes with reduction of metal compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
    • B01J13/02—Making microcapsules or microballoons
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F1/00—Metallic powder; Treatment of metallic powder, e.g. to facilitate working or to improve properties
    • B22F1/05—Metallic powder characterised by the size or surface area of the particles
    • B22F1/054—Nanosized particles
    • B22F1/0553—Complex form nanoparticles, e.g. prism, pyramid, octahedron
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82B—NANOSTRUCTURES FORMED BY MANIPULATION OF INDIVIDUAL ATOMS, MOLECULES, OR LIMITED COLLECTIONS OF ATOMS OR MOLECULES AS DISCRETE UNITS; MANUFACTURE OR TREATMENT THEREOF
    • B82B3/00—Manufacture or treatment of nanostructures by manipulation of individual atoms or molecules, or limited collections of atoms or molecules as discrete units
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites

Definitions

  • the present invention relates to a method of preparing gold nanoparticles by forming nuclei of gold particles on the outer shell of micelles and growing them using nano-scale reducing micelles containing an antioxidant as a template.
  • AuNP S Gold nanoparticles
  • AuNP S gold nanoparticles
  • AlNP S anisotropic gold nanoparticles such as polyhedral and branched gold nanoparticles having a high surface-to-volume ratio
  • SERS surface enhanced Raman scattering
  • HFOTAI 3-heptadecafluorooctyl-sulfonyl aminopropyltrimethyl-ammonium iodide
  • Polymers comprising poly [1-methyl-3- (4-vinylbenzyl) -imidazolium chloride] (Poly [1-methyl-3- (4-vinylbenzyl) -imidazolium chloride]) in water-ethanol double solvent mixtures
  • Polymeric ionic liquids PILs
  • PILs polymeric ionic liquids
  • AuNPs dendritic gold nanoparticles
  • the present inventors have completed the present invention by confirming that dendritic gold nanoparticles (AuNPs) can be easily prepared using high-branched reducing micelles prepared using antioxidants and amphiphilic copolymers as templates. It was.
  • AuNPs dendritic gold nanoparticles
  • the present invention comprises the steps of preparing a reducing micelle containing the antioxidant material by self-assembly using an amphiphilic copolymer and antioxidant (step 1), the micelle surface prepared in step 1 It provides a method for producing gold nanoparticles comprising the step of reducing the gold ions to form a nucleus according to the micellar shell structure (step 2) and growing the nucleus formed on the shell of the micelle (step 3). do.
  • step 1) is to prepare a reducing micelle containing an antioxidant
  • the reducing micelle of the present invention is an amphiphilic block copolymer or graft copolymer having a hydrophilic polymer block and a hydrophobic polymer block.
  • the coalescence of micelles takes the form of micelles or the amphiphilic lipids take the form of micelles by self-assembly, which encloses antioxidants therein.
  • polymer used in the present invention is used as a concept including an oligomer
  • the "micelle form” refers to a core composed of a hydrophobic core and a hydrophilic shell by self-assembly of an amphiphilic polymer or lipid. It is used as a concept to refer to a nano-structure in the form of a shell (core-shell).
  • self-assembly used in the present invention is a spontaneous formation of a complex structure from the basic molecule without the help of a specific enzyme or factor, in the present invention, an amphiphilic block copolymer having a hydrophilic polymer block and a hydrophobic polymer block Graft copolymers or amphiphilic lipids form micelle structures in aqueous solution by self-assembly.
  • the amphiphilic block copolymer or graft copolymer of the present invention is composed of a hydrophilic polymer block (X) composed of chains of monomer X and a hydrophobic polymer block (Y) composed of chains of monomer Y.
  • the monomer X may include ethyleneimine, alkylene oxide, oxazoline, vinylpyrrolidone, acrylamide, vinyl alcohol, amino acid, sacharide, and the like. Include.
  • these polymers can be used regardless of the molecular weight, it is more preferable to use those having a weight average molecular weight of 1,000 to 300,000.
  • the structure of the polyethyleneimine mentioned in the examples there are linear polymers and branched polymers, and the preparation of amphiphilic copolymers is possible regardless of the structure, and the weight average molecular weight is generally 25,000 or less. It is preferable to use.
  • the hydrophobic polymer block (Y) may be a biodegradable hydrophobic aliphatic polyester-based polymer.
  • monomer Y is D-lactic acid, L-lactic acid, DL-lactic acid, glycolic acid, caprolactone, amino acid, valerolactone, hydroxy butyrate, alkyl (meth) acrylate, (meth) acrylonitrile, (meth) acrylic acid
  • Unsaturated carboxylic acids such as maleic acid, vinyl acetate, vinyl propionate, vinyl butyrate, vinyl ether, styrene, p- or m-alkylstyrene, p- or m-chlorostyrene, p- or m-chloromethylstyrene, styrene Sulfonic acid and the like, and one or more selected from these monomers or a copolymer obtained by copolymerizing them are included.
  • these polymers can be used regardless of the molecular weight, it is
  • L-lactic-co-glycolic acid (hereinafter referred to as "PLGA") in aliphatic polyester, the ratio of lactic acid and glycolic acid monomer is controlled, By modifying the polymer synthesis process, a biodegradable polymer having various decomposition lifetimes can be obtained, and its properties are excellent.
  • the block copolymer is a hydrophilic polymer block and a hydrophobic polymer block ester bonds, unhydride bonds, carbamate bonds, carbonate bonds, imine or amide bonds, secondary amine bonds, urethane bonds, phosphodiester bonds or hydra It may be covalently bonded through zone bonding.
  • the polyethyleneimine (X) as the hydrophilic polymer and the aliphatic polyester polymer (Y) as the hydrophobic polymer may be a double block type of X-Y form or a triple block type composed of X-Y-X and Y-X-Y.
  • the amphiphilic lipid may be any kind of lipid capable of encapsulating an antioxidant, and dihexanoylphosphatidylcholine, N, N-dioleyl-N, N-dimethylammonium chloride (DODAC), N, N- Distearyl-N, N-dimethylammonium bromide (DDAB), N- (1- (2,3-dioleoyloxy) propyl-N, N, N-trimethylammonium chloride (DOTAP), N, N-dimethyl -(2,3-dioleoyloxy) propylamine (DODMA), N, N, N-trimethyl- (2,3-dioleoyloxy) propylamine (DOTMA), 1,2-diacyl-3- Trimethylammonium-propane (TAP), 1,2-diacyl-3-dimethylammonium-propane (DAP), 3beta- [N- (N ', N', N
  • the amphiphilic copolymer of the present invention is polyethyleneimine-g-poly (lactic-co-glycolic acid) (PEI-g-PLGA), poly (ethylene glycol) -g-polycaprolactone (PCL- g-PEG), PEG-PPG -PEG triblock copolymer (Pluronic ® F-127), die hexanoyl phosphatidylcholine (DHPC) lipids can be used, but the shape of the bi-cell or albumin -PEG, but is not limited thereto.
  • PEI-g-PLGA polyethyleneimine-g-poly (lactic-co-glycolic acid)
  • PCL- g-PEG poly (ethylene glycol) -g-polycaprolactone
  • PEG-PPG -PEG triblock copolymer Pluronic ® F-127
  • DHPC die hexanoyl phosphatidylcholine
  • the weight ratio of the hydrophobic polymer block (Y) and the hydrophilic polymer block (X) in the block copolymer or the graft copolymer is preferably 100: 1 to 1:10. If the amount of the hydrophobic polymer block (Y) increases, there is a problem that it does not form a stable nano micelles and precipitates, and if the amount of the hydrophilic polymer block (X) is too large, there is a problem that the core portion decreases, so the ratio is increased. It is preferable to adjust as described above.
  • the graft copolymer is preferably an amphiphilic graft copolymer made of a hydrophobic polyester polymer in a polyethyleneimine main chain which is a hydrophilic polymer.
  • polyethyleneimine has a linear polymer and a branched polymer according to its structure, and the formation of polymer nano micelles can be formed regardless of its structure.
  • polyethyleneimine the range which can be used depending on molecular weight is determined, and it is more preferable to use what is generally 10,000 or less.
  • Antioxidants of the present invention are ⁇ -tocopherol, polyphenols, retinol, retinyl palmitate, thioctic acid, carotenoids, vitamin C, vitamin C derivatives, caffeic acid, gallic acid and scopoletin At least one selected from the group consisting of, but is not limited thereto.
  • the vitamin C derivative of the present invention may be ethyl ascorbyl ether or potassium ascorbyl tocopheryl phosphate, but is not limited thereto.
  • the polyethyleneimine and the biodegradable polyester copolymer (PEI-g-PLGA) of the present invention forms the structure of the cationic micelle in an aqueous solution, and the size of the cationic micelle formed is measured using a light scattering method (DLS), The nano size is about 150 nm to 200 nm.
  • FIG. 1 the formation of dendritic AuNPs.
  • PEI-g-PLGA micelles containing ⁇ -tocopherol using PEI-g-PLGA as the micelle-forming amphiphilic copolymer and ⁇ -tocopherol as antioxidants were hydrated with distilled water after co-solvent evaporation to film-casting It was prepared by the method.
  • step 2) is a step of forming gold nuclei along the micelle outer structure by reducing gold ions on the surface of the micelle prepared in step 1). At this stage Au 3+ ions along the surface of the micelles begin to reduce to Au °
  • dendritic gold nanoparticles may be prepared by adding HAuCl 4 solution by the reduction gradient of the micelle surface formed by the antioxidant contained in the micelle without any additional reducing agent.
  • the formation of nuclei of gold particles can be initiated by the reduction of Au 3+ ions after the aqueous HAuCl 4 becomes AuCl 4 ⁇ through electrostatic interchange with the protonated functional groups of the cationic micelles.
  • Step 2) of the present invention is preferably carried out at room temperature.
  • step 3 is a step in which nuclei formed on the outer shell of the micelle are grown to generate gold nanoparticles.
  • nuclei of gold particles are formed on the micelle surface, large dendritic shapes may be formed by Au ° cluster formation and autocatalytic processes and / or growth of particle size by Oswald ripening. Can be.
  • the dendritic form is a structure in which a protrusion structure extending from the center of the gold nanoparticles is formed.
  • Steps 2 to 3 of the present invention are preferably made in an aqueous solution, and thus formation and growth of gold nanoparticle nuclei may occur at the surface of the micelle.
  • Gold nanoparticles prepared in the present invention is formed by a cationic micelle prepared by self-assembly using an amphiphilic copolymer as a template, the shape is formed in a structure that mimics the shell and surface shape of the micelle.
  • the structure of gold nanoparticles is a structure in which branches are developed in a dendric form from the center of nanoparticles.
  • the degree of branching and the size of the gold nanoparticles can be controlled by varying the concentration of HAuCl 4 (cyclolo (III) acid). According to one embodiment of the present invention, as the concentration of gold ions increases, the size of the gold nanoparticles increases.
  • the amount of HAuCl 4 used in the present invention is preferably 60 uM to 120 uM.
  • the amount of HAuCl 4 is less than 60 uM, the structure of the gold nanoparticles is difficult to be formed, and when the amount of HAuCl 4 is 120 uM or more, there is a problem that a dendritic structure in the form of a protrusion is formed.
  • the gold nanoparticles prepared by the present invention grow after the nucleus of the gold particles are formed along the high-branched surface structure of the micelles to have a protrusion structure that mimics the shell and surface shape of the micelles. Therefore, the gold nanoparticles prepared by the method for producing gold nanoparticles of the present invention are the same as the surface structure of micelles, and thus can be applied to visualization of micelle surface structures.
  • the gold nanoparticles having a dendritic protrusion structure prepared by the method for preparing gold nanoparticles of the present invention can be applied as probe particles for drug carriers and Raman spectrophotometers.
  • the shape and structure of the gold nanoparticles can be controlled by simple changes of micelle templates having various shapes and surface structures. Can be.
  • the structure of the gold nanoparticles is formed directly from the surface structure of micelles, it can be used as an alternative method of visualizing the surface structure of various micelles without the help of a special staining or a technique using a complicated microscope.
  • FIG. 1 shows a process of preparing gold nanoparticles using PEI-g-PLGA micelles containing ⁇ -tocopherol and a TEM image thereof.
  • FIG. 2A shows a TEM image showing the formation of dendritic AuNPs by PEI-g-PLGA micelles carrying ⁇ -tocopherol at various concentrations of HAuCl 4 and a size distribution graph of AuNPs ((a) 30uM HAuCl 4 ( b) 60 ⁇ M HAuCl 4 (c) 120 ⁇ M HAuCl 4 (d) 240 ⁇ M HAuCl 4 ).
  • FIG. 2B shows the gold nanoparticle shape of the TEM image of FIG. 2A observed at low magnification.
  • Figure 3 shows the value of the zeta-potential with AuCl 4 - concentration.
  • Figure 4A is a synthesis for 24 hours at room temperature, the gold particles by (a) using a 30 uM HAuCl 4 (b) 60 ⁇ M HAuCl 4 (c) 120 ⁇ M HAuCl 4 (d) 240 ⁇ M HAuCl 4 in accordance with one embodiment of the present invention The absorption spectrum of subsequent gold nanoparticles is shown.
  • Figure 4B shows the time-dependent absorption spectrum of gold nanoparticles after (b) synthesis of gold nanoparticles at room temperature using (b) 60 ⁇ M HAuCl 4 according to an embodiment of the present invention.
  • 6A shows TEM images and absorption spectra of gold nanoparticles formed using PEI-g-PLGA copolymer micelles.
  • FIG. 6B shows TEM images and absorption spectra of gold nanoparticles formed using PEI-g-PLGA copolymer micelles when ⁇ -tocopherol was added externally.
  • 7A is a TEM image of gold nanoparticles formed using PEG-g-PCL copolymer micelles carrying ⁇ -tocopherol.
  • FIG. 7C is a photodispersion analysis of the size distribution of gold nanoparticles formed using ⁇ -tocopherol-supported PEG-g-PCL copolymer micelles.
  • 7D shows an absorption spectrum graph of gold nanoparticles formed using ⁇ -tocopherol-supported PEG-g-PCL copolymer micelles.
  • 8A is a TEM image of gold nanoparticles formed using ⁇ -tocopherol-supported PEG-PPG-PEG triblock copolymer micelles.
  • FIG. 8B is a photodispersion analysis of the size distribution of gold nanoparticles formed using ⁇ -tocopherol-supported PEG-PPG-PEG triblock copolymer micelles.
  • 8C shows an absorption spectrum graph of gold nanoparticles formed using PEG-PPG-PEG triblock copolymer micelle loaded with ⁇ -tocopherol.
  • DHPC dihexanoylphosphatidylcholine
  • PEI Polyethyleneimine
  • Poly D, L-lactic-co-glycolic acid
  • DCC Dichlorohexyl carbodiimide
  • NHS N-hydroxyl succinimide
  • HOAuCl 4 cichlorogold acid
  • the organic solvent was purchased from Merck (Darmstadt, Germany) and used without further purification.
  • the method of preparing micelles was prepared according to a method known from MS Lee, MG Kim, YL Jang, K. Lee, TG Kim, SH Kim, TG Park, HT Kim, JH Jeong, Macromolecular Research 19 (2011) 688. .
  • Poly (lactic-co-glycolic acid, PLGA, Mw 14,000) is dissolved at a concentration of 0.11 mM tetrahydrofuran, which is dichlorohexyl carbodiimide (DCC) and N-hydroxyl.
  • DCC dichlorohexyl carbodiimide
  • the mixture was activated by mixing with succinimide (NHS), where the molar ratio of PLGA: DCC: NHS was 1: 6: 6.
  • NHS succinimide
  • the activated PLGA was precipitated in hexane and dried under reduced pressure.
  • the activated PLGA was dissolved at a concentration of 0.02 mM on a co-solvent mixed with methylene chloride / DMSO in a 1: 1 ratio.
  • branched PEI (bPEI, Mw 10,000) was prepared by dissolving at 0.01 mM in DMSO.
  • the thus prepared PLGA and bPEI were mixed in a molar ratio of 2: 1 and stirred with a stirrer at room temperature.
  • the produced PEI-g-PLGA was dialyzed in deionized water (MWCO 10,000, Spectrun, Collinso Dominguez, Calif.), And passed through a filter to freeze-dry the undissolved solution to synthesize PEI-g-PLGA.
  • Synthesis scheme was as follows, and the copolymer synthesis was confirmed using 1H-NMR and FT-IR spectroscopy.
  • the micelle containing ⁇ -tocopherol was prepared by a film casting method using the PEI-g-PLGA copolymer prepared in Preparation Example 1. More specifically, 2 mg of ⁇ -tocopherol and 10 mg of PEI-g-PLGA were dissolved in dichloromethane (DCM) and stirred at room temperature for 30 minutes. After the film was formed in the flask using a rotary evaporator under reduced pressure, distilled water was added and dissolved in an ultrasonic bath. At this time, a transparent solution without a precipitate was obtained, and the solution remained transparent even after passing through a 0.80 ⁇ m filtration filter.
  • DCM dichloromethane
  • the micelle solution of non-ionized water was placed on a 300-mesh carbon-coated copper lattice and dried at ambient temperature. The lattice was stained with 2% uranyl acetic acid and observed under a transmission electron microscope (JEM-3010, ZEOL, Tokyo, Japan). Since the PEI-g-PLGA copolymer spontaneously forms cationic micelles in an aqueous medium, the water-insoluble antioxidant, ⁇ -tocopherol, could be loaded onto the hydrophobic core of the micelles. The micelle loaded with ⁇ -tocopherol (PEI-g-PLGA / Toco) was confirmed by transmission electron microscopy (TEM) to form spherical nanoparticles with a diameter of about 120 nm.
  • TEM transmission electron microscopy
  • the nanoparticles were lyophilized, dissolved in DMSO and quantified using HPLC. Quantification using HPLC showed a loading of 11% and a loading efficiency of 73.3%.
  • mice containing ⁇ -tocopherol were prepared by the film casting method using PEG-g-PCL. More specifically, 2 mg of ⁇ -tocopherol and 10 mg of PEG-g-PCL were dissolved in dichloromethane (DCM) and stirred at room temperature for 30 minutes. After the film was formed in the flask using a rotary evaporator under reduced pressure, distilled water was added and dissolved in an ultrasonic bath. At this time, a transparent solution without a precipitate was obtained, and the solution remained transparent even after passing through a 0.80 ⁇ m filtration filter.
  • DCM dichloromethane
  • Micelles including ⁇ - tocopherol using a PEG-PPG-PEG triblock copolymer (Pluronic ® F-127) were prepared by film casting (casting) method. More particularly, the dissolved 4mg ⁇ - tocopherol and PEG-PPG-PEG triblock copolymer (Pluronic ® F-127) 10mg in dichloromethane (DCM), and the mixture was stirred at room temperature for 30 minutes. After the film was formed in the flask using a rotary evaporator under reduced pressure, distilled water was added and dissolved in an ultrasonic bath. At this time, a transparent solution without a precipitate was obtained, and the solution remained transparent even after passing through a 0.80 ⁇ m filtration filter.
  • DCM dichloromethane
  • a micelle containing ⁇ -tocopherol was prepared by a film casting method using DHPC lipid bicelle (dihexanoylphosphatidylcholine, DHPC). More specifically, 4 mg of ⁇ -tocopherol and 10 mg of DHPC lipid bicelle (dihexanoylphosphatidylcholine (DHPC)) were dissolved in dichloromethane (DCM) and stirred at room temperature for 30 minutes. After the film was formed in the flask using a rotary evaporator under reduced pressure, distilled water was added and dissolved in an ultrasonic bath. At this time, a transparent solution without a precipitate was obtained, and the solution remained transparent even after passing through a 0.80 ⁇ m filtration filter.
  • DCM dichloromethane
  • Gold nanoparticles were prepared by varying the concentration of HAuCl 4 slowly to a predetermined HAuCl 4 concentration (30 uM, 60 uM, 120 uM and 240 uM) by slowly dropping HAuCl 4 solution into PEI-g-PLGA micelle solution loaded with ⁇ -tocopherol. .
  • the color of the solution immediately changed from colorless to reddish violet after the addition of cychlorogold (III) acid (tetra-chloroaurate, HAuCl 4 ).
  • the reaction was carried out for 24 hours.
  • the resulting solution was purified by repeated centrifugation (14,000 rpm, 10 minutes) and resuspended in distilled water to prepare gold nanoparticles.
  • the prepared gold nanoparticles were confirmed by TEM, EDS, spectrophotometer and light dispersion method.
  • DHPC dihexanoylphosphatidylcholine
  • HAV 4 tetra-chloroaurate
  • TEM images of gold nanoparticles were measured using a JEOL JEM-3010 equipped with an EDS unit (Tokyo, Japan) as a transmission electron microscope (TEM).
  • Absorbance spectra were measured using an Agilent Cary 5000 UV-Vis-NIR spectrophotometer (Santa Clara, Calif.).
  • the hydrodynamic magnitude and zeta-potential were measured by a light scattering method with a He-Ne laser at a wavelength of 632 nm at a 90 ° measurement angle (zeta plus, Brookhaven Instrument Co, New York).
  • AuNP S gold nanoparticles
  • Each of the main branches developed from the center of the nanoparticles. This meant the formation of dendritic gold nanoparticle branches that spread from the PLGA core.
  • the degree of branching and the size of the gold nanoparticles could be controlled by varying the concentration of AuCl 4 ⁇ .
  • the size of the gold nanoparticles increased to 165 ⁇ 16.1 nm as the gold ion concentration increased.
  • SPR surface plasmon resonance
  • the highly branched AuNP S formed in 60 uM HAuCl 4 (sample b) showed a maximum SPR absorption at 627 nm. This is due to the relatively low aspect ratio nanorods, tripods and star-shaped gold nanoparticles with the tip of the branch protruding ((1) J. Perez-Juste, I.
  • Elemental analysis of AuNPs was performed using energy-dispersion spectroscopy (EDS). EDS patterns for gold, nitrogen and oxygen are shown in FIG. 5. Nitrogen from PEI and oxygen from the ester group of PLGA coexisted with gold in the outer shell portion (FIG. 5A) and the inner nuclear portion (FIG. 5B), respectively.
  • EDS energy-dispersion spectroscopy
  • PEI has been reported to have the ability to reduce AuCl 4 ⁇ to form AuNPs (PL Kuo, CC Chen, MW Jao, J Phys Chem B 109 (2005) 9445).
  • AuNPs prepared through PEI showed a spherical shape having a particle size of 4 nm to 25 nm.
  • PEI-g-PLGA micelles carrying ⁇ -tocopherol promoted the formation of dendritic structures from branched PEI.
  • AuNPs could also be formed by the PEI-g-PLGA copolymer itself. However, the resulting morphology of the nanoparticles was mostly spherical (Fig. 6A). The results indicate that PEI-g-PLGA may be involved in the reduction of Au 3+ to Au 0 with or without ⁇ -tocopherol, but PEI-g-PLGA without an ⁇ -tocopherol template This means that it is possible to induce gold nanoparticle formation through only transfer of reducing power, not as a role.
  • poly (ethylene oxide) -b-poly (propylene oxide) -b-poly (ethylene oxide) poly (ethylene oxide) -b-poly (propylene oxide) -b-poly (ethylene oxide, PEO-PPO-PEO )
  • polyether based block-copolymers such as poly (ethylene oxide) -b-poly (propylene oxide) from AuCl 4 - without additional reducing agent AuNP S has been reported (1) T. Sakai, P. Alexandridis, Langmuir 20 (2004) 8426. (2) S. Goy-Lopez, P. Taboada, A. Cambon, J. Juarez , C. Alvarez-Lorenzo, A. Concheiro, V. Mosquera, Journal of Physical Chemistry B 114 (2010) 66).
  • the present invention was also tested using other polymeric micelles with neutral surfaces other than PEI-g-PLGA.
  • Poly (ethyleneglycol) -g-polycaprolactone (PEG-g-PCL) micelles containing ⁇ -tocopherol could also form AuNPs (FIG. 7A).
  • PEG-g-PCL polycaprolactone
  • the EDS pattern of gold nanoparticles prepared using PEG-g-PCL as a template showed that gold or oxygen atoms on PEG or PCL blocks co-directed PEG-g-PCL (FIG. 7B).
  • the surface structure of AuNPs formed from PEG-g-PCL template is characterized by the surface morphology of PEG-g-PCL micelles predicted by computer-aided coarse-grain molecular simulation (G. Srinivas, DE Discher, ML Klein, Nat. Mater 3 (2004) 638.) showed great similarity. Therefore, according to the method for producing gold nanoparticles of the present invention, it can be applied to visualize the fine structure of the micelle surface.
  • PEG-PPG-PEG triblock copolymer (Pluronic ® F-127) micelle.
  • a PEG-PPG-PEG triblock copolymer (Pluronic ® F-127) involve ⁇ - tocopherol micelles could also form a AuNPs (Fig. 8).
  • DHPC micelles containing ⁇ -tocopherol could also form AuNPs (FIG. 9).

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Abstract

La présente invention concerne un procédé de préparation de nanoparticules d'or en formant des noyaux de nanoparticules d'or sur l'enveloppe de micelles à l'aide de micelles de réduction à l'échelle nanométrique qui comprennent un antioxydant, utilisées comme moule, et en faisant croître ensuite les noyaux des nanoparticules d'or. Les nanoparticules d'or préparées selon la présente invention présentent une structure dentée imitant la forme d'une enveloppe et d'une surface des micelles en formant et en faisant croître ensuite les noyaux des nanoparticules d'or selon une structure de surface à haute arborescence des micelles. De plus, les nanoparticules d'or préparées selon le procédé de préparation des nanoparticules d'or de la présente invention présentent la même structure de surface que celle des micelles et peuvent être appliquées à la visualisation d'une structure de surface des micelles. En outre, les nanoparticules d'or présentant une structure dentée préparées selon le procédé de préparation des nanoparticules d'or de la présente invention peuvent être appliquées sous la forme d'une particule sonde destinée à un système d'administration de médicaments et à une spectrophotométrie Raman.
PCT/KR2013/009152 2013-01-09 2013-10-14 Procédé de préparation de nanoparticules d'or utilisant des micelles comme moule WO2014109459A1 (fr)

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CN109517182A (zh) * 2017-09-20 2019-03-26 上海双洳生物科技有限公司 一种聚乙烯醇多齿聚合物的合成方法
CN115351288A (zh) * 2022-08-23 2022-11-18 西北工业大学 一种金纳米花及其制备方法和应用

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