# US 12,760,193 B2 · Methacrylated nanoparticles and related method > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,760,193 B2 - Document ID: US12760193B2 - Status: Granted - Kind: B2 - Application number: 18/026,818 - Filed: 2021-09-20 - Published: 2023-10-12 - Granted: 2026-10-13 - Earliest claimed: 2020-09-18 - Applicants: Ryan Roeder; Lan Li - Inventors: Ryan Roeder; Lan Li - Web page: https://patentgrep.com/patent/US12760193B2 ## CPC - C09D 11/101: Inks specially adapted for printing processes involving curing by wave energy or particle radiation, e.g. with UV-curing following the printing - A61L 27/047: {Other specific metals or alloys not covered by A61L27/042 - A61L27/045 or A61L27/06} - A61L 27/16: obtained by reactions only involving carbon-to-carbon unsaturated bonds - A61L 27/34: Macromolecular materials - A61L 27/507: {for artificial blood vessels (apparatus for applying cells on a blood vessel prosthesis A61F2/062)} - C09D 11/033: characterised by the solvent - C09D 11/037: characterised by the pigment - C09D 11/107: from unsaturated acids or derivatives thereof - A61L 2400/12: Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces - B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery - B82Y 40/00: Manufacture or treatment of nanostructures - C09D: COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR (cosmetics A61K; processes for applying liquids or other fluent materials to surfaces, in general, B05D; staining wood B27K5/02; glazes or vitreous enamels C03C; natural resins, French polish, drying-oils, driers, turpentine, per se, C09F; polishing compositions other than French polish, ski waxes C09G; adhesives or use of materials as adhesives C09J; materials for sealing or packing joints or covers C09K3/10; materials for stopping leaks C09K3/12; processes for the electrolytic or electrophoretic production of coatings C25D) - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) - B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES ## Abstract A photocrosslinkable agent includes at least one methacrylate-modified nanoparticle that includes a plurality of molecules attached to surface of a nanoparticle. At least a portion of the molecules includes a molecule that includes a nanoparticle surface attachment ligand a terminal methacrylate ligand. At least a portion of the molecules may include a second molecule that includes a nanoparticle surface attachment ligand and a hydrophilic terminal ligand, wherein the methacrylate-modified nanoparticle has water solubility that is controlled by the relative amounts of the terminal methacrylate ligand and the hydrophilic terminal ligand. The photocrosslinkable agent may be crosslinked within a polymer network by a one-step process, with minimal disruption to the molecular network or crosslinking density and may be formulated for use as one or more of an imaging contrast agent, a therapeutic, or a reinforcement, a transducer. ## Claims ### Claim 1 A photocrosslinkable agent comprising: a. at least one water-soluble methacrylate-modified nanoparticle (100) comprising: i. a nanoparticle; and ii. a plurality of molecules attached to a surface of the nanoparticle, each of the plurality of molecules comprising a nanoparticle surface attachment ligand (1), a first portion of the plurality of molecules including a terminal methacrylate ligand (103), and a second portion of the plurality of molecules including a hydrophilic terminal ligand (2), wherein any one of the plurality of molecules may include more than one nanoparticle surface attachment ligand and more than one terminal ligand. ### Claim 2 (depends on 1) The photocrosslinkable agent according to claim 1, wherein the nanoparticle surface attachment ligand (1) is selected from the group consisting of thiols, amines, alcohols, silanes, carboxylates, phosphonates, and combinations thereof, and wherein the hydrophilic terminal ligand (2) is selected from the group consisting of thiols, amines, alcohols, carboxylates, silanes, phosphonates, acrylates, epoxides, and combinations thereof. ### Claim 3 (depends on 1) The photocrosslinkable agent according to claim 1, wherein the methacrylate-modified nanoparticle (100) has water solubility that is controlled by the relative amounts of the terminal methacrylate ligand (103) and the hydrophilic terminal ligand (2). ### Claim 4 (depends on 1) The photocrosslinkable agent according to claim 1, wherein the nanoparticles have a shape selected from the group consisting of nanospheres, nanorods, nanoplates, nanoshells, nanotubes, nanocages, nanostars, and combinations thereof, and wherein the nanoparticles are composed of at least one material selected from the group consisting of a metal, a ceramic, a semiconductor, a polymer, and combinations thereof, or wherein the nanoparticles are composed of a combination of at least two materials selected from the group consisting of a metal, a ceramic, a semiconductor, and a polymer, each material forming at least a portion of the nanoparticle, or wherein the nanoparticles have a core-shell structure or a Janus structure. ### Claim 5 (depends on 1) The photocrosslinkable agent according to claim 1, wherein the nanoparticles are composed of a metal or a metal portion, the metal or metal portion of the nanoparticle selected from the group consisting of magnesium, aluminum, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, nitinol, copper, zinc, selenium, zirconium, molybdenum, palladium, silver, gadolinium, tantalum, tungsten, iridium, platinum, gold, bismuth, and alloys and combinations thereof. ### Claim 6 (depends on 1) The photocrosslinkable agent according to claim 1, wherein the nanoparticles are composed of a ceramic or a ceramic portion, the ceramic or ceramic portion of the nanoparticle selected from the group consisting of boron nitride, magnesium oxide, aluminum oxide, aluminum nitride, silicon dioxide, silicon nitride, titanium dioxide, titanium carbide, hematite or iron(III) oxide, magnetite or iron(II,III) oxide, copper oxide, zinc oxide, strontium titanate, zirconium oxide, cerium oxide, gadolinium oxide, tantalum oxide, barium titanate, barium sulfate, hafnium oxide, tungsten oxide, hydroxyapatite, calcium-deficient hydroxyapatite, carbonated calcium hydroxyapatite, beta-tricalcium phosphate, alpha-tricalcium phosphate, amorphous calcium phosphate, octacalcium phosphate, tetracalcium phosphate, biphasic calcium phosphate, anhydrous dicalcium phosphate, dicalcium phosphate dihydrate, anhydrous monocalcium phosphate, monocalcium phosphate monohydrate, calcium silicates, calcium aluminates, calcium carbonate, calcium sulfate, zinc phosphate, zinc silicates, aluminosilicates, zeolites, bioglass 45, bioglass 52S4.6, and combinations thereof. ### Claim 7 (depends on 1) The photocrosslinkable agent according to claim 1, wherein the nanoparticles are composed of a semiconductor or a semiconductor portion, the semiconductor or semiconductor portion of the nanoparticle selected from the group consisting of silicon, graphene, zinc oxide, zinc sulfide, zinc selenide, gallium arsenide, cadmium oxide, cadmium sulfide, cadmium selenide, and combinations thereof. ### Claim 8 (depends on 1) The photocrosslinkable agent according to claim 1, wherein the nanoparticles are composed of a polymer or a polymer portion, the polymer or polymer portion of the nanoparticle selected from the group consisting of polyaryletherketone (PAEK), polyetheretherketone (PEEK), polyetherketonekteone (PEKK), polyetherketone (PEK), polytetrafluoroethylene (PTFE) polyethylene, high density polyethylene (HDPE), ultra-high molecular weight polyethylene (UHMWPE), low density polyethylene (LDPE), polyethylene oxide (PEO), polyethylene terephthalatepolyurethane (PET), polypropylene, polypropylene oxide (PPO), polysulfone, polyethersulfone, polyphenylsulfone, poly(vinyl chloride) (PVC), polyoxymethylene, polyacrylonitrile (PAN), polystyrene, poly(vinyl alcohol) (PVA), poly(DL-lactide) (PDLA), poly(L-lactide) (PLLA), poly(glycolide) (PGA), poly(ε-caprolactone) (PCL), poly(dioxanone) (PDO), poly(glyconate), poly(hydroxybutyrate) (PHB), poly(hydroxyvalerate (PHV), poly(orthoesters), poly(carboxylates), poly(propylene fumarate), poly(phosphates), poly(carbonates), poly(anhydrides), poly(iminocarbonates), poly(phosphazenes), polyimides, polyamides, polysiloxanes, polyphosphates, citric-acid based polymers, polyacrylics, polymethylmethacrylate (PMMA), bisphenol A-glycidyl methacrylate (bis-GMA), tri(ethylene glycol) dimethacrylate (TEG-DMA), poly(2-hydroxyethyl methacrylate) (HEMA)poly(acrylic acid) (PAA), polyethylene glycol (PEG), polysaccharides, gelatin, collagen, alginate, chitosan, dextran, carboxymethyl cellulose, polypeptides, copolymers thereof, and combinations thereof. ### Claim 9 A photocrosslinkable ink for forming a material or structure, comprising: a. a suitable solvent comprising water; b. a plurality of water-soluble methacrylate-modified nanoparticles, each of the methacrylate-modified nanoparticles comprising: i. a nanoparticle; and ii. a plurality of molecules attached to a surface of the nanoparticle, each of the plurality of molecules comprising a nanoparticle surface attachment ligand (1) and at least a portion of the plurality of molecules comprising a terminal methacrylate ligand (103); and at least a portion of the molecules comprising a hydrophilic terminal ligand (2), wherein any one of the plurality of molecules may include more than one nanoparticle surface attachment ligand and more than one terminal ligand, c. optionally, a plurality of methacrylate-modified macromolecules (107); and d. a photoinitiator. ### Claim 10 (depends on 9) The photocrosslinkable ink according to claim 9 comprising the plurality of methacrylate-modified macromolecules (107), wherein the plurality of methacrylate-modified macromolecules (107) is selected from the group consisting of polymers, oligomers or a combination thereof selected from the group consisting of gelatin-methacrylate (gelMA), collagen-methacrylate (colMA), alginate-methacrylate (algMA), hyaluronic acid-methacrylate (HAMA), dextran-methacrylate (dexMA), chitosan-methacrylate (chiMA), chondroitin sulfate-methacrylate (CSMA), heparin-methacrylate (hepMA), carboxymethyl cellulose-methacrylate (CMCMA), polyethylene glycol dimethacrylate (PEGDA), polyurethane-methacrylate, polyacrylic acid (PAA), polymethyl methacrylate (PMMA), poly(2-hydroxyethyl methacrylate) (HEMA), bisphenol A-glycidyl methacrylate (bis-GMA), tri(ethylene glycol) dimethacrylate (TEG-DMA), diethyleneglycol diacrylate (DEGDA), and combinations thereof. ### Claim 11 (depends on 9) The photocrosslinkable ink according to claim 9, wherein the methacrylate-modified nanoparticle (100) has water solubility that is controlled by the relative amounts of the terminal methacrylate ligand (103) and the hydrophilic terminal ligand (2). ### Claim 12 (depends on 1) A photocrosslinked material comprising the photocrosslinkable agent-according to claim 1, comprising: (i) a plurality of water-soluble methacrylate-modified nanoparticles, wherein at least a portion of the plurality of the terminal methacrylate ligands (103) on the nanoparticles (101) are photocrosslinked, resulting in a covalent linkage (109) between the methacrylate-modified nanoparticles (100); (ii) at least one water-soluble methacrylate-modified nanoparticle (100) and a plurality of water-soluble methacrylate-modified macromolecules (107), wherein at least a portion of the plurality of the terminal methacrylate ligands (103) on the at least one nanoparticle are photocrosslinked with at least a portion of the methacrylate-modified macromolecules (107), the photocrosslinked material comprising a covalent linkage between the photocrosslinked methacrylate-modified nanoparticles (100) and methacrylate-modified macromolecules (107); or (iii) a combination of (i) and (ii). ### Claim 13 (depends on 12) The photocrosslinked material according to claim 12, wherein the photocrosslinked material comprises a plurality of methacrylate-modified macromolecules (107), and the photocrosslinked material exhibits at least one or more properties selected from the group consisting of crosslinking density, rheology, mechanical stiffness, mechanical strength, swelling, degradation kinetics, and any combination thereof, and wherein at least one or more of the properties are not substantially altered by the presence of the photocrosslinkable agent as compared to a photocrosslinked product formed by photocrosslinking the methacrylate-modified macromolecules (107) in the absence of the photocrosslinkable agent. ### Claim 14 A method for providing a photocrosslinkable agent, the method comprising: a. providing a nanoparticle; b. providing a first bifunctional molecule (105) comprising a nanoparticle surface attachment ligand (1) that is attached to a surface of the nanoparticle, and a terminal ligand comprising a hydrophilic terminal ligand (2) capable of covalent linking to a terminal ligand of another molecule; c. providing a second bifunctional molecule (106) comprising a terminal methacrylate ligand (103) and a terminal ligand comprising a coupling ligand (4) capable of covalent linking to the hydrophilic terminal ligand (2) of the first molecule; and d. covalently linking the hydrophilic terminal ligand (2) of the first molecule to the coupling ligand (4) of the second molecule, optionally in the presence of a coupling agent or catalyst, forming a water-soluble methacrylate-modified nanoparticle, wherein any one of the first, second or both first and second bifunctional molecules may include more than one nanoparticle surface attachment ligand and more than one terminal ligand. ### Claim 15 (depends on 14) The method of claim 14, wherein covalent linking to the coupling ligand (4) of the second molecule is carried out under conditions that result in incomplete conversion of the hydrophilic terminal coupling ligands (2) such that the nanoparticle is surface functionalized with a conjugated molecule comprising a nanoparticle surface attachment ligand (1) and a terminal methacrylate ligand (103), and the first molecule comprising the nanoparticle surface attachment ligand (1) and hydrophilic terminal ligand (2), and wherein the methacrylate-modified nanoparticle (100) has a water solubility that is controlled by the relative amounts of the conjugated molecule and the first molecule. ### Claim 16 (depends on 12) The photocrosslinked material according to claim 12, wherein the photocrosslinked material is photocrosslinked at a frequency in the range from ultraviolet to near-infrared and an intensity in a range from 2 to 30 mW/cm2 for 0.5 min to 24 hours. ### Claim 17 (depends on 14) The method for providing a photocrosslinkable agent according to claim 14, wherein: a. the first bifunctional molecule (105) comprises a carboxylate terminal ligand as the hydrophilic terminal ligand (2); b. the second bifunctional molecule (106) comprises a terminal amine coupling ligand (4) capable of covalent linking to the carboxylate terminal group of the hydrophilic terminal ligand (2) of the first bifunctional molecule; and c. covalently linking the hydrophilic terminal ligand (2) of the first bifunctional molecule to the terminal coupling ligand (4) of the second bifunctional molecule, in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide or N-hydroxysulfosuccinimide (NHS) in alcohol, wherein a molar ratio of EDC:NHS:MA is in a range of 15:6:6 to 50:20:20. ### Claim 18 (depends on 1) The photocrosslinkable agent according to claim 1, wherein the nanoparticles are composed of a noble metal. ### Claim 19 (depends on 17) The method according to claim 17, wherein the total time for the coupling reaction, which influences the degree of methacrylation and hydrophilicity of the methacrylate-modified nanoparticles, is from 3 to 48 h. ### Claim 20 (depends on 17) The method according to claim 17, wherein the coupling reaction pH between 4.0-8.5.