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  Water-soluble nanoparticles stabilized with multi-functional group ligands and method of preparation thereofUSPTO Application #: 20080038361Title: Water-soluble nanoparticles stabilized with multi-functional group ligands and method of preparation thereof Abstract: Disclosed are water-soluble nanoparticles. The water-soluble nanoparticles are each surrounded by a multifunctional group ligand including an adhesive region, a cross linking region, and a reactive region. In the water-soluble nanoparticles, the cross-linking region of the multifunctional group ligand is cross-linked with another cross-linking region of a neighboring multifunctional group ligand. Furthermore, the present invention provides a method of producing water-soluble nanoparticles, which includes (1) synthesizing water-insoluble nanoparticles in an organic solvent, (2) dissolving the water insoluble nanoparticles in a first solvent and dissolving water-soluble multifunctional group ligands in a second solvent, (3) mixing the two solutions from the step (2) to substitute surfaces of the water-insoluble nanoparticles with the multifunctional group ligands and dissolving a mixture in an aqueous solution to conduct a separation process, and (4) cross-linking the substituted multifunctional group ligands with each other. (end of abstract)
Agent: Sheridan Ross PC - Denver, CO, US Inventors: Jin-Woo Cheon, Young-Wook Jun, Jin-Sil Choi USPTO Applicaton #: 20080038361 - Class: 424490000 (USPTO) Related Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Preparations Characterized By Special Physical Form, Particulate Form (e.g., Powders, Granules, Beads, Microcapsules, And Pellets), Coated (e.g., Microcapsules) The Patent Description & Claims data below is from USPTO Patent Application 20080038361. Brief Patent Description - Full Patent Description - Patent Application Claims
TECHNICAL FIELD [0001] The present invention relates, in general, to water-soluble nanoparticles and, more particularly, to water-soluble nanoparticles, which are each surrounded by a multifunctional group ligand (L.sub.I-L.sub.II-L.sub.III) including an adhesive region (L.sub.I), a cross-linking region (L.sub.II), and a reactive region (L.sub.III), and in which the cross-linking region of the multifunctional group ligand is cross-linked with another cross-linking region of a neighboring multifunctional group ligand. [0002] Furthermore, the present invention pertains to a method of producing water-soluble nanoparticles, which includes (1) synthesizing water-insoluble nanoparticles in an organic solvent, (2) dissolving the water-insoluble nanoparticles in a first solvent and dissolving water-soluble multifunctional group ligands in a second solvent, (3) mixing two solutions in the step (2) to substitute surfaces of the water-insoluble nanoparticles with the multifunctional group ligands and dissolving a mixture in an aqueous solution to conduct a separation process, and (4) cross-linking the substituted multifunctional group ligands with each other. BACKGROUND ART [0003] Used to adjust and control a substance at an atomic or molecular level, nanotechnology is suitable to create novel substances and materials, and applied to various fields, such as electronic, material, communication, mechanical, medical, agricultural, energy, and environmental fields. [0004] Currently, development of various types of nanotechnologies is in progress, and the nanotechnology is usually classified into the following three categories. The first category relates to a technology to synthesize ultrafine novel substances and matter using a nano-material. The second category relates to a technology to produce a device which assures predetermined functions by combining or arranging nano-sized materials. The third category relates to a technology to apply a nanotechnology, which is called a nano-bio, to bioengineering. [0005] Particularly, in nano-bio fields, nanoparticles are used to specifically kill cancer cells, boost an immune reaction, fuse cells, deliver genes or drugs, conduct diagnosis and the like. In order to apply the nanoparticles to the above applications, the nanoparticles must have portions, to which active components are capable of adhering, and must be stably delivered and dispersed in vivo, that is, in a water-soluble environment. Many technologies have lately been developed to satisfy such conditions. [0006] U.S. Pat. No. 6,274,121 discloses paramagnetic nanoparticles including metals, such as iron oxides, to which inorganic materials, having binding sites that are capable of being coupled with tissue-specific binding substances and diagnostically or pharmaceutically active materials, adhere. [0007] U.S. Pat. No. 6,638,494 pertains to paramagnetic nanoparticles containing metals, such as iron oxides, and discloses a method of preventing nanoparticles from cohering and precipitating in the gravity or magnetic fields, in which specific carboxylic acid adheres to surfaces of the nanoparticles. Examples of the above carboxylic acid include aliphatic dicarboxylic acid, such as maleic acid, tartaric acid, and glucaric acid, or aliphatic polycarboxylic acid, such as citric acid, cyclohexane, and tricarboxylic acid. [0008] U.S. Pat. No. 6,649,138 discloses a method of improving the water-soluble property of nanoparticles, in which a multiply amphiphilic dispersant layer is formed on surfaces of the hydrophobic nanoparticles having semiconductor or metal materials. The multiply amphiphilic dispersant is exemplified by (1) a hydrophobic backbone having hydrophilic branched chains, (2) a hydrophilic backbone having hydrophobic branched chains, or (3) a hydrophobic or hydrophilic backbone simultaneously having hydrophilic and hydrophobic branched chains. [0009] U.S. Patent Application No. 2004/0033345 discloses a method of capsulizing nanoparticles, in which hydrophobic ligand layers are formed around metals or semiconductors, using micelles to dissolve the nanoparticles in an aqueous solution. At this time, the micelles consist of hydrophilic shells and hydrophobic cores. [0010] U.S. Patent Application No. 2004/0058457 suggests functional nanoparticles which are surrounded by monolayers, and in which bifunctional peptides adhere to the monolayers and various biopolymers including DNA and RNA are bound to the peptides. [0011] However, the water-soluble nanoparticles produced according to the above method, have the following disadvantages. In U.S. Pat. Nos. 6,274,121, and 6,638,494, and U.S. Patent Application No. 2004/0058457, the nanoparticles are synthesized in aqueous solution. In such a case, it is difficult to control the sizes of the nanoparticles, and the synthesized nanoparticles have a nonuniform size distribution. Furthermore, since they are synthesized at low temperatures, crystallinities of the nanoparticles are low and non-stoichiometric compounds are apt to be generated. Additionally, surfaces of the nanoparticles are coated with a monomolecular surface stabilizer, but bonding strengths between the stabilizer and the nanoparticles are not high, and thus, the nanoparticles are less stable in aqueous solution. The water-soluble nanoparticles of U.S. Pat. No. 6,649,138 and U.S. Patent Application No. 2004/0033345 are surrounded by amphiphilic polymers, thus having significantly increased diameters in comparison with inorganic nanoparticles. Further, successful application examples of these nanoparticles are limited to semiconductor nanoparticles. DISCLOSURE OF THE INVENTION [0012] Accordingly, an object of the present invention is to provide water-soluble nanoparticles which are highly stable in aqueous solution and have low toxicity to living bodies, thereby being applied to various fields, such as bio diagnosis and treatment, and electronic materials, and a method of preparation thereof. [0013] In order to accomplish the above object, the present inventors added multifunctional group ligands, each of which includes (a) an adhesive region bonded to nanoparticles, (b) a cross-linking region stabilizing the nanoparticles in an aqueous solution, and (c) a reactive region capable of being bonded to active components, to the nanoparticles gained from an organic solvent, thereby producing nanoparticles which are stable in aqueous solution and are capable of being bonded to various active components. [0014] The present invention provides water-soluble nanoparticles, which are each surrounded by a multifunctional group ligand including an adhesive region, a cross-linking region, and a reactive region, and in which the cross-linking region of the multifunctional group ligand is cross-linked with another cross-linking region of a neighboring multifunctional group ligand. [0015] Furthermore, the present invention provides a method of producing water-soluble nanoparticles, which includes (1) synthesizing water-insoluble nanoparticles in an organic solvent, (2) dissolving the water-insoluble nanoparticles in a first solvent and dissolving water-soluble multifunctional group ligands in a second solvent, (3) mixing two solutions in the step (2) to substitute surfaces of the water-insoluble nanoparticles with the multifunctional group ligands and dissolving a mixture in an aqueous solution to conduct a separation process, and (4) cross-linking the substituted multifunctional group ligands with each other. BRIEF DESCRIPTION OF THE DRAWINGS [0016] The above and other objects, features and other advantages of the present invention will be more clearly understood from the following detailed description taken in conjunction with the accompanying drawings, in which: [0017] FIG. 1 illustrates the production of water-soluble nanoparticles from water-insoluble nanoparticles according to the present invention; [0018] FIG. 2 schematically illustrates the water-soluble nanoparticles according to the present invention; [0019] FIG. 3 illustrates the production process of water-soluble iron oxide nanoparticles surrounded by dimercaptosuccinic acid according to the present invention; [0020] FIG. 4 illustrates the solubility of iron oxide nanoparticles, surrounded by an organic surface stabilizer, in an organic solvent, and the solubility of the water-soluble iron oxide nanoparticles, surrounded by water-soluble multifunctional group ligands, in an aqueous solution; Continue reading... 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