# US 9,872,916 B2 · Facile method for making non-toxic biomedical compositions comprising hybrid metal-polymer microparticles

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- Number: US 9,872,916 B2
- Document ID: US9872916B2
- Status: Granted
- Kind: B2
- Application number: 14/390,945
- Filed: 2013-04-05
- Published: 2015-06-18
- Granted: 2018-01-23
- Earliest claimed: 2012-04-06
- Assignees: University of North Texas Office of Economic Development and Technology Transfer
- Applicants: University of North Texas
- Inventors: Mohammad A. Omary; Sreekar Marpu
- Web page: https://patentgrep.com/patent/US9872916B2

## CPC

- A61K 49/0091: {Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer}
- A61K 9/501: {Inorganic compounds}
- A61K 9/5026: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 33/38: Silver; Compounds thereof
- A61K 47/58: obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
- 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 49/0065: {the luminescent/fluorescent agent having itself a special physical form, e.g. gold nanoparticle}
- B22F 1/102: Metallic powder coated with organic material
- B82Y 30/00: Nanotechnology for materials or surface science, e.g. nanocomposites
- G01N 33/5005: {involving human or animal cells (immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025)}
- G01N 33/536: with immune complex formed in liquid phase
- Y10T 436/25: including sample preparation
- 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)
- B22F: WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER (making alloys by powder metallurgy C22C); APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

The present invention includes photochemical method of making hybrid metal-polymer microparticles in an aqueous, biocompatible solution by providing a metal (I) composition and one or more polymeric materials; applying an electromagnetic radiation to the metal (I) composition; converting the metal (I) composition to a metal (0) composition; forming one or more hybrid metal-polymer microparticles from the metal (0); capping the one or more hybrid metal-polymer microparticles; and stabilizing the one or more hybrid metal-polymer microparticles with the one or more polymeric materials to prevent agglomeration.

## Claims

### Claim 1

A method of making a plasmonic hybrid metal-polymer microparticle complex comprising the steps of:
forming a hybrid metal-polymer microparticle with a tunable near-infrared (NIR) plasmon absorption in an aqueous, biocompatible solution by
providing an aqueous biocompatible solution;
combining a metal (I) composition and one or more polymeric materials in the aqueous biocompatible solution;
applying an electromagnetic radiation for 30-40 minutes, to the metal (I) composition to convert the metal (I) composition to a metal (0) composition;
forming one or more hybrid metal-polymer microparticles from the metal (0);
capping the one or more hybrid metal-polymer microparticles; and
stabilizing the one or more hybrid metal-polymer microparticles with the one or more polymeric materials to prevent agglomeration and to provide the NIR plasmon absorption of the one or more hybrid metal-polymer microparticles between 700 nm-1200 nm; and
forming one or more stabilized hybrid metal-polymer microparticles.

### Claim 2 (depends on 1)

The method of claim 1, further comprising the step of adding one or more binding agents to the one or more hybrid metal-polymer microparticles to form a diagnosis complex that binds to a specific agent, wherein the one or more binding agents comprise one or more antibodies or oligonucleotides.

### Claim 3 (depends on 1)

The method of claim 1, further comprising the step of adding one or more agents that enhance Raman scattering and identifying one or more small biological molecules using surface enhanced Raman scattering.

### Claim 4 (depends on 1)

The method of claim 1, further comprising the step of adding an active agent and a pharmaceutical carrier to form a pharmaceutical plasmonic hybrid metal-polymer microparticle composition for delivery of an active agent.

### Claim 5 (depends on 1)

The method of claim 1, wherein the metal (0) comprises at least one metal atom selected from the group consisting of aluminum, antimony, arsenic, barium, beryllium, bismuth, cadmium, calcium, cerium, chromium, cobalt, dysprosium, erbium, europium, gadolinium, gallium, hafnium, holmium, indium, iridium, iron, lanthanum, lead, lithium, lutetium, magnesium, manganese, mercury, molybdenum, neodymium, nickel, niobium, osmium, palladium, platinum, potassium, praseodymium, rhenium, rhodium, rubidium, ruthenium, samarium, scandium, strontium, tantalum, technetium, terbium, titanium, thallium, thorium, thulium, tin, tungsten, uranium, vanadium, ytterbium, yttrium, zinc, and zirconium.

### Claim 6 (depends on 1)

The method of claim 1, wherein the metal (I) composition comprises a gold (I) complex, silver (I) complex or salt, copper (I) complex or salt, or combinations thereof.

### Claim 7 (depends on 1)

The method of claim 1, wherein the metal (I) composition is made by adding a metal (I) precursor comprising Au(tetrahydrothiophene)Cl, AuMe2SCl, Au(CO)Cl, AgNO3 or AgPF6 or Cu(PPh3)3X complexes.

### Claim 8 (depends on 1)

The method of claim 1, wherein the one or more polymer stabilizers comprise agarose, hydrogels, PAA (poly acrylic acid), PVA (poly vinyl alcohol), Chitosan, PNIPAM (Poly-N-isopropyl acrylamide), substituted PNIPAM, PAMAM (Polyamidoamine), PEG (Poly ethylene glycol), alginic acid, HPC (hydroxyl propyl cellulose), a crude phospholipid extract isolated from soybeans or a combination thereof.

### Claim 9 (depends on 1)

The method of claim 1, wherein the one or more polymeric materials comprise Chitosan, Polyacrylic acid, Alginic acid, PEG, PVA, Agarose, albumin, bovine serum albumin (BSA), human albumin, synthetic albumin, HPC, PNIPAM, Nylon, polyurethane, polyacrylonitrile or a crude phospholipid extract isolated from soybeans.

### Claim 10

A method of making a plasmonic hybrid metal-polymer microparticle complex comprising the steps of:
forming a hybrid metal-polymer microparticle with a tunable near-infrared (NIR) plasmon absorption in an aqueous, biocompatible solution by
providing an aqueous biocompatible solution;
combining a metal (I) composition wherein the metal (I) is silver and one or more polymeric materials in the aqueous biocompatible solution wherein one or more polymeric materials comprise Nylon, polyurethane, or polyacrylonitrile;
applying an electromagnetic radiation for 30-40 minutes to the metal (I) composition to convert the metal (I) composition to a metal (0) composition;
forming one or more hybrid metal-polymer microparticles from the metal (0);
capping the one or more hybrid metal-polymer microparticles; and
stabilizing the one or more hybrid metal-polymer microparticles with the one or more polymeric materials to prevent agglomeration and to provide the NIR plasmon absorption of the one or more hybrid metal-polymer microparticles between 700 nm-1200 nm; and
forming one or more stabilized hybrid metal-polymer microparticles.

### Claim 11 (depends on 1)

The method of claim 1, wherein the hybrid metal-polymer microparticle composition is varied in size, shape or both.

### Claim 12 (depends on 1)

The method of claim 1, further comprising the step adjusting one or more parameters selected from the group consisting of pH, ionic strength, temperature, centrifugation, reaction vessel material, optical filters, and combinations thereof, to adjust at least one of the tuning of the plasmon absorption energies or intensities and corresponding variation of at least one of size or shape of the one or more hybrid metal-polymer microparticles to adjust a plasmon absorption energy, an intensity or a combination thereof.

### Claim 13 (depends on 1)

The method of claim 1, wherein the hybrid metal-polymer microparticle composition is varied in NIR plasmon absorption by varying a time of exposure and concentrations of the one or more polymeric materials and the metal (I) composition.

### Claim 14 (depends on 1)

The method of claim 1, wherein the electromagnetic radiation is in the form of UV light, Sunlight, microwave radiation, far infrared radiation, near infrared radiation, visible radiation, x-rays, gamma rays, or high-energy gamma rays.

### Claim 15 (depends on 4)

The method of claim 4, wherein the active agent is an agent that binds an antibody, a cell surface, or a small biological molecule.

### Claim 16 (depends on 4)

The method of claim 4, wherein the active agent is delivered by a phase transition change in the pharmaceutical plasmonic hybrid metal-polymer microparticle composition; by a phase transition in the hybrid metal-polymer microparticle resulting from an electromagnetic change; or by a phase transition in the hybrid metal-polymer microparticle resulting from a thermal change.

### Claim 17

A hybrid metal-polymer microparticle composite made by:
providing an aqueous biocompatible solution;
combining a metal (I) composition and one or more polymeric materials and one or more nanofibers;
applying an electromagnetic radiation for 30-40 minutes to the metal (I) composition;
converting the metal (I) composition to a metal (0) composition;
forming one or more hybrid metal-polymer microparticles from the metal (0);
capping the one or more hybrid metal-polymer microparticles;
stabilizing the one or more hybrid metal-polymer microparticles with the one or more polymeric materials to prevent agglomeration;
forming a hybrid metal-polymer microparticle composite; and
tuning of a near-infrared (NIR) plasmon absorption of the one or more hybrid metal-polymer microparticles between 700 nm-1200 nm by varying time of exposure, concentrations of the one or more polymeric materials, concentrations of the metal (I) composition or a combination thereof.

### Claim 18 (depends on 17)

The hybrid metal-polymer microparticle composite of claim 17, wherein the metal (I) composition is silver to form an antipathogenic biocompatible polymer composition.

### Claim 19 (depends on 17)

The hybrid metal-polymer microparticle composite of claim 17, wherein the one or more polymer stabilizers comprises agarose, hydrogels, PAA (poly acrylic acid), PVA (poly vinyl alcohol), Chitosan, PNIPAM (Poly-N-isopropyl acrylamide), substituted PNIPAM, PEG (Poly ethylene glycol), alginic acid, HPC (hydroxyl propyl cellulose), a crude phospholipid extract isolated from soybeans or a combination thereof.

### Claim 20 (depends on 17)

The hybrid metal-polymer microparticle composite of claim 17, further comprising the step of forming the hybrid metal-polymer microparticle composite into a filter, a fiber, a cloth, a water filter, or a textile.

### Claim 21 (depends on 1)

The method of claim 1, wherein the one or more polymeric materials comprise PNIPAM-aa (poly-N-isopropyl acrylamide-acrylic acid), PNIPAM-allylamine (Poly-N-isopropyl acrylamide-allylamine), or PNIPAM-SH.

### Claim 22 (depends on 19)

The hybrid metal-polymer microparticle composite of claim 19, wherein the substituted PNIPAM comprises PNIPAM-aa (poly-N-isopropyl acrylamide-acrylic acid), PNIPAM-allylamine (Poly-N-isopropyl acrylamide-allylamine), or PNIPAM-SH.