# US 11,298,428 B2 · Nanocarrier for selective fluorescence labeling of cancer cell and preparation method therefor

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- Number: US 11,298,428 B2
- Document ID: US11298428B2
- Status: Granted
- Kind: B2
- Application number: 16/462,098
- Filed: 2017-02-20
- Published: 2020-08-27
- Granted: 2022-04-12
- Earliest claimed: 2016-11-18
- Assignees: Seoul National University R&Db Foundation
- Applicants: Seoul National University R&Db Foundation
- Inventors: Kang Won Lee; Yoon Jeong; Sara Lee
- Web page: https://patentgrep.com/patent/US11298428B2

## CPC

- A61K 47/6907: {the form being a microemulsion, nanoemulsion or micelle}
- A61K 49/0021: {the fluorescent group being a small organic molecule}
- A61K 41/0061: {5-aminolevulinic acid-based PDT: 5-ALA-PDT involving porphyrins or precursors of protoporphyrins generated in vivo from 5-ALA}
- A61K 47/551: {one of the codrug's components being a vitamin, e.g. niacinamide, vitamin B3, cobalamin, vitamin B12, folate, vitamin A or retinoic acid}
- A61K 49/0036: {Porphyrins (used in photodynamic therapy A61K41/0071 or A61K41/0076; used as targeting group or modifying agent for targeting a therapeutic compound A61K47/546)}
- A61K 49/0082: {micelle, e.g. phospholipidic micelle and polymeric micelle}
- G01N 33/57595: {involving intracellular compounds}
- G01N 33/582: {with fluorescent label}
- 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)
- 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

An embodiment of the present invention provides a nanocarrier in a micelle structure, a pharmaceutical composition for diagnosis of cancer, comprising the same nanocarrier, and a method for preparing the same nanocarrier. The nanocarrier is obtained by dispersing a water-in-oil nanoemulsion containing an oil phase ingredient, a surfactant, and an aqueous phase ingredient inclusive of a cancer cell fluorescence-inducing substance and a cancer cell-targeting polysaccharide in water to remove the oil phase ingredient, whereby the nanocarrier includes the aqueous phase ingredient.

## Claims

### Claim 1

A micelle structured nanocarrier comprising an aqueous phase as an inner phase and comprising a surfactant on the surface thereof, wherein the micelle structured nanocarrier is obtained by dispersing a water-in-oil nanoemulsion comprising an oil phase ingredient, a surfactant, and an aqueous phase ingredient in water to remove the oil phase ingredient, wherein the aqueous phase comprises a cancer cell fluorescence-inducing substance and a cancer cell-targeting polysaccharide,
wherein the cancer cell-targeting polysaccharide is entangled to each other to encapsulate the cancer cell fluorescence-inducing substance thereby forming an interpenetrating polymer network structure, wherein the cancer cell-targeting polysaccharide protrudes from a surface of the nanocarrier,
wherein the micelle structured nanocarrier has an average size of 200 nm or less.

### Claim 2 (depends on 1)

The nanocarrier of claim 1, wherein the aqueous phase ingredient comprises the cancer cell fluorescence-inducing substance and the cancer cell-targeting polysaccharide in a weight ratio of 1:1.

### Claim 3 (depends on 1)

The nanocarrier of claim 1, wherein the nanocarrier has a zeta potential value of −10 mV to −30 mV or 10 mV to 30 mV.

### Claim 4 (depends on 1)

The nanocarrier of claim 1, wherein the nanoemulsion comprises 70% by weight to 80% by weight of the oil phase ingredient, 10% by weight to 20% by weight of the aqueous phase ingredient, and 5% by weight to 15% by weight of the surfactant, based on the total weight of the nanoemulsion.

### Claim 5 (depends on 1)

The nanocarrier of claim 1, wherein the surfactant is a single surfactant or a cosurfactant.

### Claim 6 (depends on 1)

The nanocarrier of claim 1, wherein the surfactant is a cosurfactant having an HLB value of 6 to 9.

### Claim 7 (depends on 1)

The nanocarrier of claim 1, wherein the surfactant is a mixture comprising sorbitan fatty acid ester and polyoxyethylene sorbitan fatty acid ester and having an HLB value of 6 to 9.

### Claim 8 (depends on 1)

The nanocarrier of claim 1, wherein the cancer cell fluorescence-inducing substance is selected from the group consisting of heme, hemin, zinc protoporphyrin, magnesium protoporphyrin, hematoporphyrin, benzoporphyrin, metalloporphyrin, 5-aminolevulinic acid, texaphyrins, chlorins, purpurins, bacteriochlorins, phthalocyanine, naphthalocyanine, and any combination thereof.

### Claim 9 (depends on 1)

The nanocarrier of claim 1, wherein the cancer cell-targeting polysaccharide is hyaluronic acid or a cancer cell-targeting ligand-binding polysaccharide.

### Claim 10 (depends on 9)

The nanocarrier of claim 9, wherein the cancer cell-targeting polysaccharide is the cancer cell-targeting ligand-binding polysaccharide, and
wherein the ligand of the cancer cell-targeting ligand-binding polysaccharide is selected from the group consisting of an aptamer, an antibody, a peptide, and a folic acid; and
wherein the polysaccharide of the cancer cell-targeting ligand-binding polysaccharide is selected from the group consisting of alginic acid, chitosan, pectin, beta-glucan, cellulose, gelatin, hemicellulose, galactomannan, inulin, gum, and chitin.

### Claim 11 (depends on 9)

The nanocarrier of claim 9, wherein the cancer cell-targeting polysaccharide is the cancer cell-targeting ligand-binding polysaccharide, and
wherein the cancer cell-targeting ligand-binding polysaccharide is a folic acid-binding alginic acid.

### Claim 12 (depends on 1)

The nanocarrier of claim 1, wherein the cancer cell fluorescence-inducing substance is 5-aminolevulinic acid, and the cancer cell-targeting polysaccharide is hyaluronic acid.

### Claim 13 (depends on 1)

The nanocarrier of claim 1, wherein the oil phase ingredient is selected from the group consisting of soybean oil, olive oil, grape seed oil, canola oil, corn oil, mineral oil, silicone oil, castor oil, paraffin oil, and any combination thereof.

### Claim 14 (depends on 1)

A method of contrasting cancer cells, the method comprising:
administering an effective amount of the nanocarrier of claim 1 to a subject in need thereof.

### Claim 15 (depends on 14)

The method of claim 14, wherein the cancer is selected from the group consisting of a brain tumor, lung cancer, stomach cancer, and ovarian cancer.

### Claim 16 (depends on 1)

A method of preparing the nanocarrier of claim 1, the method comprising:
preparing the oil phase ingredient;
preparing the surfactant;
preparing a first aqueous phase ingredient including the cancer cell-targeting polysaccharide;
preparing a second aqueous phase ingredient including the cancer cell fluorescence-inducing substance;
preparing a water-in-oil nanoemulsion by mixing and stirring the oil phase ingredient, the surfactant, the first aqueous phase ingredient, and the second aqueous phase ingredient; and
re-dispersing the water-in-oil nanoemulsion in water to remove the oil phase ingredient, thereby separating nanocarrier.