Nanoparticles and preparation method thereof

Abstract

The present invention relates to a nanoparticle, a preparation method thereof, a stone removing device and its application. The nanoparticle includes a nanoparticle core made of a magnetic material, and a nanoparticle shell formed by attaching a surface modifier monomer to the nanoparticle core with an initiator and/or a crosslinking agent. The prepared nanoparticle can surround stones in ureter, and then small stone remaining in body can be removed quickly without damage from the body under the action of an externally applied magnetic field, that is, the stone can be drawn and moved without injuring ureteral wall, and meanwhile the nanoparticles are placed conveniently without shift.

What is claimed: 
     
         1 . A nanoparticle, the nanoparticle comprises:
 a nanoparticle core made of a magnetic material; and   a nanoparticle shell formed by in-situ modification of a surface modifier monomer to the surface of the nanoparticle core with an initiator and/or a crosslinking agent;   wherein the surface of the nanoparticle after surface modification and functionalization has an amide bond or a carboxyl group, and the weight percentage of shell is 0.5-45% (excluding end points), with regard to the weight of the nanoparticle.   
     
     
         2 . The nanoparticle according to  claim 1 , wherein the weight percentage of shell is 1-40%, more preferably 2-40%, further more preferably 1-15%, much further more preferably 2-15%, most preferably 1%, 2%, 15% or 40%, with regard to the weight of the nanoparticle. 
     
     
         3 . The nanoparticle according to  claim 1 , wherein the nanoparticle core has a diameter of 2-50 nm, and a weight percentage of 30-95% with regard to the whole weight of the nanoparticle, and its magnetic material includes a compound of Fe 3+ , Fe 2+ , Mn 2+ , Ni 2+ , or a metal element selected from iron, nickel, copper, cobalt, platinum, gold, europium, gadolinium, dysprosium, terbium, or a composite or oxide of the aforementioned metals, or any one of the above items or a combination of two or more of the above items, preferably Fe 3+ , Fe 2+ , Mn 2+ , Ni 2+  compounds, more preferably Fe 3+  and Fe 2+  in a ratio of 15% to 85%, preferably 1:2.5 to 1.5:1. 
     
     
         4 . The nanoparticle according to any one of  claims 1 - 3 , wherein the surface modifier includes a hydrophilic surface modifier, a hydrophobic surface modifier, a photosensitive, a thermosensitive surface modifier or a pH sensitive surface modifier with function response, wherein the hydrophilic surface modifier includes acrylic acid, methacrylic acid, isobutyl acrylamide or poly N-substituted isopropylacrylamide; the hydrophobic surface modifier includes olefins, preferably polystyrene, polyethylene or oleic acid; the photosensitive surface modifier is selected from the group consisting of azos and quinolines and benzophenones (PVBP), preferably vinyl benzophenone; the thermosensitive surface modifier is selected from the group consisting of amphiphilic polymers with an amide bond, preferably polyacrylamide or poly N-substituted isopropylacrylamide; the pH-sensitive surface modifier is selected from the group consisting of polymers with a carboxyl group and a quaternary ammonium salt, preferably polyacrylic acid, dimethylaminoethyl ester and dimethylaminopropyl methacrylate; the particle is of spherical shape, rod shape or diamond shape. 
     
     
         5 . The nanoparticle according to any one of  claims 1 - 3 , wherein the crosslinking agent includes 3-(methacryloyloxy)propyltriethoxysilane, divinylbenzene, diisocyanate or N,N-methylenebisacrylamide, and the initiator includes 3-chloropropionic acid, CuCl, 4,4′-dinonyl-2,2-bipyridine or potassium persulfate. 
     
     
         6 . A nanoparticle, the nanoparticle comprises:
 a nanoparticle core made of a magnetic material; and   a nanoparticle shell formed by in-situ modification of a surface modifier monomer to the surface of the nanoparticle core with an initiator and/or a crosslinking agent;   wherein the surface of the nanoparticle after surface modification and functionalization has an amide bond or a carboxyl group, and the method for preparing the magnetic nanoparticle core is co-precipitation method, wherein the mode of adding the surface modifier monomer is a continuous dropping with assistance of an electronic pump.   
     
     
         7 . The nanoparticle according to  claim 6 , wherein the nanoparticle core has a diameter of 2-50 nm, and a weight percentage of 30-95% with regard to the whole weight of the nanoparticle, and its magnetic material includes a compound of Fe 3+ , Fe 2+ , Mn 2+ , Ni 2+ , or a metal element selected from iron, nickel, copper, cobalt, platinum, gold, europium, gadolinium, dysprosium, terbium, or a composite or oxide of the aforementioned metals, or any one of the above items or a combination of two or more of the above items, preferably Fe 3+ , Fe 2+ , Mn 2+ , Ni 2+  compounds, more preferably Fe 3+  and Fe 2+  in a ratio of 15% to 85%, preferably 1:2.5 to 1.5:1. 
     
     
         8 . The nanoparticle according to  claim 7 , wherein the mutual forces for surrounding and crosslinking between the nanoparticles and the stone include: van der Waal's force that form an interacting surrounding, hydrophobic interaction, adsorption and surface deposition; chemical bonds formed between carboxyl-stone, including hydrogen bonds, ester bonds, amide bonds and other covalent bonds; interacting physical and chemical entanglements between chains and chemical crosslinking between chains. 
     
     
         9 . The nanoparticle according to any one of  claims 6 - 8 , wherein the surface modifier includes a hydrophilic surface modifier with function response, a hydrophobic surface modifier with function response, a photosensitive surface modifier with function response, a thermosensitive surface modifier with function response or a pH sensitive surface modifier with function response, wherein the hydrophilic surface modifier includes acrylic acid, methacrylic acid, isobutyl acrylamide or poly N-substituted isopropylacrylamide; the hydrophobic surface modifier includes olefins, preferably polystyrene, polyethylene or oleic acid; the photosensitive surface modifier is selected from the group consisting of azos and quinolines and benzophenones (PVBP), preferably vinyl benzophenone; the thermosensitive surface modifier is selected from the group consisting of amphiphilic polymers with an amide bond, preferably polyacrylamide or poly N-substituted isopropylacrylamide; the pH-sensitive surface modifier is selected from the group consisting of polymers with a carboxyl group and a quaternary ammonium salt, preferably polyacrylic acid, dimethylaminoethyl ester and dimethylaminopropyl methacrylate; the shell accounts for 0.5-45% by weight (excluding end points) of the nanoparticle, preferably 1-40%, more preferably 2-40%, further more preferably 1-15% or 2-15%, most preferably 1%, 2%, 15% or 40%; preferably, the particle is of spherical shape, rod shape or diamond shape. 
     
     
         10 . The nanoparticle according to any one of  claims 6 - 9 , wherein the crosslinking agent includes 3-(methacryloyloxy)propyltriethoxysilane, divinylbenzene, diisocyanate or N,N-methylenebisacrylamide, and the initiator includes 3-chloropropionic acid, CuCl, 4,4′-dinonyl-2,2-bipyridine or potassium persulfate. 
     
     
         11 . A method for preparing the nanoparticle according to any one of  claims 1 - 10 , wherein said method includes the following steps:
 a) preparing the nanoparticle core using the magnetic material;   b) forming the nanoparticle shell by in-situ linking the surface modifier monomer to the nanoparticle core by the initiator and/or crosslinking agent, thereby forming the nanoparticle.   
     
     
         12 . The method according to  claim 11 , wherein the magnetic material includes a compound of Fe 3+ , Fe 2+ , Mn 2+ , Ni 2+ , or a metal element selected from iron, nickel, copper, cobalt, platinum, gold, europium, gadolinium, dysprosium, terbium, or a composite or oxide of the aforementioned metals, or any one of the above items or a combination of two or more of the above items, preferably Fe 3 O 4 , MnFe 2 O 4 , γ-Fe 2 O 3  or other nanoscale sized ferrite particles, more preferably FeCl 3 .6H 2 O and FeCl 2 .4H 2 O in a molar ratio of 15% to 85%, preferably 1:2.5 to 1.5:1, including the following steps:
 dissolving a proportion of the metal salt-containing material in water; 
 feeding nitrogen to expel oxygen in the solution; 
 adding a catalyst at a room temperature of 10-40° C., preferably 30° C., to adjust the pH to 7-12, preferably 10; 
 keeping agitation and reaction for 10-60 minutes; and 
 reacting under condition of 40-100° C., preferably 70° C. water bath, for 20-40 minutes, then separating with a magnet and drying to obtain the magnetic nanoparticle core. 
 
     
     
         13 . The method according to  claim 12 , wherein when aqueous ammonia is used as the catalyst to prepare the nanoparticle, the method for dropping the aqueous ammonia is performed in a continuous and dropwise manner with assistance of an electronic pump at a speed of 20-100 drops/minute, preferably 40-60 drops/minute; and when the magnetic material is a liquid monomer material, the liquid monomer is added in a dropwise and continuous manner with assistance of an electronic pump, and the reaction is carried out under agitation with a speed of 100-1000 revolutions/minute, preferably 500-700 revolutions/minute. 
     
     
         14 . The method according to any one of  claims 11 - 13 , wherein said method further includes hydrophobic surface modification based on the obtained nanoparticle core, including steps of:
 dispersing the prepared nanoparticle core in an aqueous solution, and adding with an xylene solution of 3-chloropropionic acid, polystyrene, CuCl and 4,4′-dinonyl-2,2-bipyridine, wherein the molar ratio between the solution of the nanoparticle core and the reaction solution is 1:1;   reacting the mixture at 130° C. under continuous agitation for 15-30 hours, preferably 24 hours; and   collecting the nanoparticles with a magnet, washing repeatedly with toluene to obtain hydrophobic polystyrene-surrounded magnetic iron oxide nanoparticles.   
     
     
         15 . The method according to any one of  claims 11 - 13 , wherein said method further includes hydrophilic surface modification based on the obtained nanoparticle core, including steps of:
 dispersing the prepared nanoparticle core in xylene, and added with a silane coupling agent, wherein the nanoparticles, xylene and silane coupling agent are added in a ratio of 95:5;   reacting under nitrogen protection at 20-100° C., preferably at 80° C., for 2-5 hours, preferably for 3 hours;   washing with an alcoholic solvent and drying for 12 hours, dispersing in an aqueous solution under ultrasonic condition, adding with potassium persulfate;   reacting under nitrogen protection at 40-80° C. for 10 minutes, then adding with acrylic acid to continue reaction at 40-80° C. for 1 hour, preferably at the reaction temperature of 70° C.; and   magnetically separating, washing and drying to obtain the polyacrylic acid-modified hydrophilic nanoparticle.   
     
     
         16 . The method according to any one of  claims 11 - 13 , wherein said method further includes performing a photosensitive, thermosensitive and pH-sensitive surface modification based on the resulting nanoparticle core or on a hydrophilic surface thereof, or performing a hydrophilic, hydrophobic, light-sensitive, thermosensitive, pH-sensitive co-modification based on the nanoparticle core, wherein the re-modification on the hydrophilic surface includes the steps of:
 dissolving and dispersing the polyacrylic acid-modified magnetic nanoparticle in an alcoholic solvent, adding with a photosensitive monomer such as vinylbenzophenone, a thermosensitive monomer such as N-isopropylacrylamide, or a pH-sensitive monomer such as dimethylaminopropyl methacrylate or a blend monomer of acrylic acid and styrene, continuously reacting at 40-80° C. for 1 hour, preferably at a reaction temperature of 70° C.; and magnetically separating, washing and drying to obtain a photosensitive, thermosensitive or pH-Sensitive functional monomer-modified magnetic nanoparticle.   
     
     
         17 . A stone removal device, comprising the nanoparticle according to any one of  claims 1 - 10 , and a magnetic probe rod system with an flexible end, wherein the magnetic probe rod system comprises a handle, a flexible rod, a magnetic field source and a magnetically permeable material. 
     
     
         18 . The stone removal device according to  claim 17 , wherein the magnetic probe rod system is provided with an AC or DC power supply, a power switch, a DC battery compartment or an AC plug on the handle; the flexible rod is made of a polymer material, preferably the flexible rod includes a permanent magnet at its rear end and optionally a flexible magnetically permeable material at the end of the flexible rod. 
     
     
         19 . An article, the article comprising the nanoparticle according to any one of  claims 1 - 10 , wherein the nanoparticle is in form of a solution or a powder, preferably a solution. 
     
     
         20 . A use of the nanoparticle according to any one of  claims 1  to  10  in the manufacture of an article for in-vivo stone removal, preferably the article is used for urinary stone removal in a human or animal.