# US 2013/0095187 A1 · Composition for nucleic acid delivery using metal nanoparticles and preparing method thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2013/0095187 A1 - Document ID: US20130095187A1 - Status: Published application - Kind: A1 - Application number: 13/430,882 - Filed: 2012-03-27 - Published: 2013-04-18 - Earliest claimed: 2011-10-14 - Assignees: Postech Academy-Industry Foundation - Inventors: Sei Kwang HAHN; Min-Young Lee; Kitae Park; Ku Su Kim; Hwiwon Lee - Web page: https://patentgrep.com/patent/US20130095187A1 ## CPC - A61K 31/713: Double-stranded nucleic acids or oligonucleotides - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/5115: {Inorganic compounds} - A61K 9/5146: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides} - A61K 9/5161: {Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin} - A61K 9/5192: {Processes} - A61K 31/7088: Compounds having three or more nucleosides or nucleotides - A61K 47/59: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes - A61K 47/61: the organic macromolecular compound being a polysaccharide or a derivative thereof - A61K 47/6923: {the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb} - B82Y 40/00: Manufacture or treatment of nanostructures - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES ## Abstract The present invention relates to a composition for nucleic acid delivery and a method for preparing the same, more particularly to a composition for nucleic acid delivery having excellent stability in the body environment and excellent intracellular delivery efficiency of nucleic acid, and enabling target directed delivery of nucleic acid, and a method for preparing the same. ## Claims ### Claim 1 A composition for nucleic acid delivery comprising positively charged metal nanoparticles; and a nucleic acid layer, a cationic polymer layer and an anionic polymer layer formed by coating of nucleic acid, cationic polymer and anionic polymer on the surface of the metal nanoparticles by electrostatic layer by layer self assembly. ### Claim 2 (depends on 1) The composition for nucleic acid delivery according to claim 1, wherein the metal nanoparticle is gold nanoparticle, silver nanoparticle, or magnetic nanoparticle having positive charge introduced on the surface. ### Claim 3 (depends on 1) The composition for nucleic acid delivery according to claim 1, wherein the metal nanoparticle includes positive charge introducing material selected from the group consisting of dopamine, polyethyleneglycol (PEG), and cysteine, bound to the surface. ### Claim 4 (depends on 1) The composition for nucleic acid delivery according to claim 1, wherein the metal nanoparticle includes cysteine bound to the surface. ### Claim 5 (depends on 1) The composition for nucleic acid delivery according to claim 1, wherein the nucleic acid is small interfering ribonucleic acid (siRNA), antisense nucleic acid, or nucleic acid aptamer. ### Claim 6 (depends on 1) The composition for nucleic acid delivery according to claim 1, wherein the nucleic acid is small interfering ribonucleic acid (siRNA), antisense nucleic acid, or nucleic acid aptamer, consisting of 5 to 200 base pairs. ### Claim 7 (depends on 1) The composition for nucleic acid delivery according to claim 1, wherein the nucleic acid is included in the mole ratio of 40 to 48:1 (nucleic acid: metal nanoparticles) to the metal nanoparticles. ### Claim 8 (depends on 1) The composition for nucleic acid delivery according to claim 1, wherein the cationic polymer is polyethyleneimine, chitosan, or polyamidoamine. ### Claim 9 (depends on 1) The composition for nucleic acid delivery according to claim 1, wherein the cationic polymer is polyethyleneimine with a molecular weight of 10 kDa to 25 kDa. ### Claim 10 (depends on 1) The composition for nucleic acid delivery according to claim 1, wherein the anionic polymer is selected from the group consisting of hyaluronic acid, dextran sulfate, heparin, heparan sulfate, chondroitin, chondroitin sulfate, keratan sulfate, dermatan sulfate, and a pharmaceutically acceptable salt thereof. ### Claim 11 (depends on 1) The composition for nucleic acid delivery according to claim 1, wherein the anionic polymer is hyaluronic acid with a molecular weight of 10 kD to 100 kD, or a pharmaceutically acceptable salt thereof. ### Claim 12 (depends on 1) The composition for nucleic acid delivery according to claim 1, wherein the composition for nucleic acid delivery comprises 90 to 110 parts by weight of the metal nanoparticles, 3.28 to 3.93 parts by weight of the nucleic acid, 3.24 to 3.89 parts by weight of the cationic polymer, and 50.45 to 61.66 parts by weight of the anionic polymer. ### Claim 13 A method for preparing a composition for nucleic acid delivery, comprising: reacting metal nanoparticles with positive charge introducing material to introduce positive charge on the surface of the metal nanoparticles; coating nucleic acid on the surface of the positive charge introduced metal nanoparticle surface to form a metal nanoparticle/nucleic acid composite; coating cationic polymer on the metal nanoparticle/nucleic acid composite to form a metal nanoparticle/nucleic acid/cationic polymer composite; and coating anionic polymer on the metal nanoparticle/nucleic acid/cationic polymer composite to form a metal nanoparticle/nucleic acid/cationic polymer/anionic polymer composite, wherein the nucleic acid, cationic polymer, and anionic polymer is coated by electrostatic layer by layer self assembly. ### Claim 14 (depends on 13) The method for preparing a composition for nucleic acid delivery according to claim 13, wherein the metal nanoparticle is gold nanoparticle, silver nanoparticle, or magnetic nanoparticle. ### Claim 15 (depends on 13) The method for preparing a composition for nucleic acid delivery according to claim 13, wherein the positive charge introducing material is dopamine, polyethyleneglycol (PEG), or cysteine. ### Claim 16 (depends on 13) The method for preparing a composition for nucleic acid delivery according to claim 13, wherein the step of forming the metal nanoparticle/nucleic acid composite comprises adding a solution including the metal nanoparticles to a solution including the nucleic acid. ### Claim 17 (depends on 16) The method for preparing a composition for nucleic acid delivery according to claim 16, wherein the metal nanoparticles are added such that a mole ratio of the nucleic acid coated on the metal nanoparticles and the metal nanoparticles becomes 40 to 48:1 (nucleic acid: metal nanoparticles). ### Claim 18 (depends on 13) The method for preparing a composition for nucleic acid delivery according to claim 13, wherein the nucleic acid is small interfering ribonucleic acid (siRNA), antisense nucleic acid, or nucleic acid aptamer. ### Claim 19 (depends on 13) The method for preparing a composition for nucleic acid delivery according to claim 13, wherein the cationic polymer is coated at N/P ratio of 1 to 5 to the metal nanoparticle/nucleic acid composite. ### Claim 20 (depends on 13) The method for preparing a composition for nucleic acid delivery according to claim 13, wherein the cationic polymer is polyethyleneimine, chitosan, or polyamidoamine. ### Claim 21 (depends on 13) The method for preparing a composition for nucleic acid delivery according to claim 13, wherein the anionic polymer is coated at a mass ratio of 10 to 30:1 to the cationic polymer of the metal nanoparticle/nucleic acid/cationic polymer composite. ### Claim 22 (depends on 13) The method for preparing a composition for nucleic acid delivery according to claim 13, wherein the anionic polymer is selected from the group consisting of hyaluronic acid, dextran sulfate, heparin, heparan sulfate, chondroitin, chondroitin sulfate, keratan sulfate, dermatan sulfate, and a pharmaceutically acceptable salt thereof.