# US 8,784,895 B2 · Multifunctional metal nanoparticles having a polydopamine-based surface and methods of making and using the same

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- Number: US 8,784,895 B2
- Document ID: US8784895B2
- Status: Granted
- Kind: B2
- Application number: 13/420,189
- Filed: 2012-03-14
- Published: 2012-09-20
- Granted: 2014-07-22
- Earliest claimed: 2011-03-15
- Assignees: Northwestern University
- Applicants: Phillip B. Messersmith; Kvar C. L. Black, IV; Ji Yi; Jose G. Rivera
- Inventors: Phillip B. Messersmith; Kvar C. L. Black, IV; Ji Yi; Jose G. Rivera
- Web page: https://patentgrep.com/patent/US8784895B2

## CPC

- A61K 41/0052: {Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy}
- A61K 9/0092: {Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes}
- A61K 9/1611: {Inorganic compounds}
- A61K 9/1641: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers}
- A61K 9/1676: {having a drug-free core with discrete complete coating layer containing drug (adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921)}
- A61K 9/1682: {Processes}
- A61K 9/5094: {Microcapsules containing magnetic carrier material, e.g. ferrite for drug targeting}
- A61K 9/51: Nanocapsules; {Nanoparticles; (nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00)}
- A61K 31/69: Boron compounds
- A61K 33/00: Medicinal preparations containing inorganic active ingredients
- A61K 33/26: Iron; Compounds thereof
- A61K 33/38: Silver; Compounds thereof
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 39/40: bacterial
- A61K 41/0057: {Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/6923: {the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb}
- A61K 49/1857: {the organic macromolecular compound being obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. PLGA}
- A61K 49/1875: {coated or functionalised with an antibody}
- A61N 5/062: {Photodynamic therapy, i.e. excitation of an agent}
- A61P 31/04: Antibacterial agents
- A61P 35/00: Antineoplastic agents
- B22F 1/054: Nanosized particles
- B22F 1/16: Metallic particles coated with a non-metal (coated with lubricating or binding agents or with organic material B22F1/10)
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- B82Y 40/00: Manufacture or treatment of nanostructures
- C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 16/30: from tumour cells
- G01N 21/4795: {spatially resolved investigating of object in scattering medium (in vivo A61B)}
- G01N 21/554: {detecting the surface plasmon resonance of nanostructured metals, e.g. localised surface plasmon resonance}
- G01N 33/54346: {Nanoparticles}
- G01N 33/553: Metal or metal coated
- G01N 33/587: {Nanoparticles}
- B82Y 15/00: Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
- 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)
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- 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)

## Abstract

The present invention provides nanoparticles including a metallic core having a length along each axis of from 1 to 100 nanometers and a coating disposed on at least part of the surface of the metallic core, wherein the coating comprises polydopamine, along with methods for making and using such nanoparticles. The metallic core may be gold, silver or iron oxide and the polydopamine coating may have other substances bound to it, such as silver, targeting ligands or antibodies, or other therapeutic or imaging contrast agents. The disclosed nanoparticles can be targeted to cells for treating cancer or bacterial infections, and for use in diagnostic imaging.

## Claims

### Claim 1

A nanoparticle comprising:
(a) a metallic core comprising gold or silver, wherein said core is a nanorod having a substantially cylindrical shape, wherein the substantially cylindrical nanorod has a length of from 1 to 100 nanometers and a diameter of from 1 to 50 nanometers; and
(b) a coating disposed on at least part of the surface of the metallic core, wherein the coating comprises polydopamine.

### Claim 2 (depends on 1)

The nanoparticle of claim 1, wherein the coating is disposed on the entire surface of the metallic core.

### Claim 3 (depends on 1)

The nanoparticle of claim 1, wherein the metallic core consists essentially of gold.

### Claim 4 (depends on 1)

The nanoparticle of claim 1, wherein the coating further comprises silver, iron oxide, or a mixture thereof.

### Claim 5 (depends on 1)

The nanoparticle of claim 1, further comprising one or more antibodies, polyethylene glycol, functionalized polyethylene glycol, or a mixture thereof bound to the coating.

### Claim 6 (depends on 5)

The nanoparticle of claim 5, wherein the antibody is an anti-cancer cell surface receptor antibody or an anti-bacterial surface antibody.

### Claim 7 (depends on 1)

The nanoparticle of claim 1, further comprising a polymer, a polysaccharide, a sugar-containing peptoid, a pharmaceutical agent, or a mixture thereof bound to the coating.

### Claim 8 (depends on 7)

The nanoparticle of claim 7, wherein the pharmaceutical agent is an anti-cancer agent or an anti-microbial agent.

### Claim 9 (depends on 1)

A method of making the nanoparticle of claim 1, comprising contacting a substantially cylindrical metallic core comprising gold or silver, wherein said core is a nanorod having a length along each axis of from 1 to 100 nanometers and a diameter of from 1 to 50 nanometers, with an alkaline solution comprising dopamine, whereby a polydopamine coating is formed on the surface of the metallic core.

### Claim 10 (depends on 9)

The method of claim 9, wherein the metallic core is a nanorod having a substantially cylindrical shape that consists essentially of gold.