# US 2014/0193837 A1 · Luminescent nanoparticle compositions

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- Number: US 2014/0193837 A1
- Document ID: US20140193837A1
- Status: Published application
- Kind: A1
- Application number: 14/124,057
- Filed: 2012-06-14
- Published: 2014-07-10
- Earliest claimed: 2011-06-15
- Assignees: Board of Regents, The University of Texas System
- Inventors: Jie Zheng
- Web page: https://patentgrep.com/patent/US20140193837A1

## CPC

- G01N 33/587: {Nanoparticles}
- A61K 49/0065: {the luminescent/fluorescent agent having itself a special physical form, e.g. gold nanoparticle}
- G01N 33/54346: {Nanoparticles}
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- B82Y 15/00: Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
- C09K 2211/188: of other metals not provided for in one of the previous groups
- Y10S 977/773: Nanoparticle, i.e. structure having three dimensions of 100 nm or less
- Y10S 977/92: Detection of biochemical
- 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)
- 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)
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- C09K: MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

A composition is disclosed which is capable of being used for detection, comprising a noble metal nanoparticle. The inventive compositions exhibit little interaction with serum proteins while exhibiting pH-dependent adsorption onto live cell membranes. The nanoparticles of the claimed invention are capable of interacting with cell membranes, which in turn permits the advantages of nanoparticle bio-imaging to be extended to many pH dependent biological processes such as targeting acidic tumor microenvironment.

## Claims

### Claim 1

A composition comprising a fluorescent noble metal nanoparticle, wherein the surface of the noble metal nanoparticle is coated with a first anti-fouling ligand and a second pH-dependent ligand, and wherein the noble metal nanoparticle is about 0.1 nm to 3 nm in diameter.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the noble metal nanoparticle comprises between 2 and 1000 noble metal atoms.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the noble metal is selected from the group consisting of gold, silver, and copper.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the composition is contacted with a molecule of interest.

### Claim 5 (depends on 4)

The composition of claim 4, wherein the molecule of interest is present in a biological sample.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the anti-fouling ligand is a protein, polymer, zwitterionic material or a mixed charge material.

### Claim 7 (depends on 6)

The composition of claim 6, wherein the anti-fouling ligand is glutathione.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the pH-dependent ligand is a protonated ligand.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the pH-dependent ligand comprises one or more thiol groups.

### Claim 10 (depends on 1)

The composition of claim 1, wherein the pH-dependent ligand is hydrophobic.

### Claim 11 (depends on 10)

The composition of claim 10, wherein the pH-dependent ligand is cysteamine or cysteamine analogs.

### Claim 12 (depends on 10)

The composition of claim 10, wherein the pH-dependent ligand is 3-amino-2-(aminomethyl) propane-1-thiol, 4-aminobenzenethiol, pyridine-4-thiol, 1-amino-5-methyl-1H-imidazole-2-thiol, 5-amino-2-mercapto-1-me-1H-imidazole-4-carboxan, aminopropane thiol, aminobutane thiol, aminoethane thiol, mercaptoethanol, mercaptopropanol, mercaptobutanol, mercaptoundecanol, (11-mercaptoundecyl)phosphonoperoxoic acid or 11-aminoundecane thiol.

### Claim 13 (depends on 1)

The composition of claim 1, wherein the nanoparticle further comprises a pH-dependent peptide.

### Claim 14 (depends on 13)

The composition of claim 13, wherein the pH-dependent peptide comprises pH low insertion peptide (pHLIP) (SEQ ID NO:1).

### Claim 15 (depends on 1)

The composition of claim 1, wherein the composition binds to the surface of a cell in a pH-dependent manner.

### Claim 16 (depends on 15)

The composition of claim 15, wherein the cell is a tumor cell.

### Claim 17 (depends on 16)

The composition of claim 16, wherein the tumor is an acidic tumor.

### Claim 18 (depends on 16)

The composition of claim 16, wherein the tumor is a non-acidic tumor.

### Claim 19 (depends on 1)

The composition of claim 1, wherein the ratio of the first ligand and the second ligand ranges from 1:0.25 to 1:3.

### Claim 20 (depends on 1)

A method of detecting a surface of a cell, the method comprising the steps of:
contacting the composition of claim 1 with a surface of a cell;
adsorbing the composition comprising fluorescent noble metal nanoparticles on to the surface of the cell; and
detecting the presence of the fluorescent nanoparticle on the surface of the cell.

### Claim 21 (depends on 20)

The method of claim 20, wherein the cell is a tumor cell.

### Claim 22 (depends on 21)

The method of claim 21, wherein the tumor is an acidic tumor.

### Claim 23 (depends on 21)

The method of claim 21, wherein the tumor is a non-acidic tumor.
