Nanoparticles for targeting acid tumor microenvironments

Patent metadata

Field	Value
Publication number	US-10012653-B2
Application number	US-201214124057-A
Country	US
Kind code	B2
Filing date	Jun 14, 2012
Priority date	Jun 15, 2011
Publication date	Jul 3, 2018
Grant date	Jul 3, 2018

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.

First claim

What is claimed is:

1. A composition comprising a fluorescent noble metal nanoparticle, said nanoparticle comprising a noble metal core, wherein the surface of the noble metal core is coated with a glutathione and cysteamine or a cysteamine analog at a glutathione-to-cysteamine/cysteamine analog ratio of from 1:2.5 to 1:1, wherein the noble metal nanoparticle is defined as comprising between 2 and 1000 noble metal atoms, or having a diameter of 0.3 nm to 3 nm, and wherein the noble metal nanoparticle binds to a molecule of interest on a tumor cell in an acidic tumor microenvironment defined by a pH of between 5.3 and 7.0.

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

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

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

5. The composition of claim 4 , wherein the pH-dependent peptide comprises pH low insertion peptide (pHLIP).

6. A method of detecting a surface of a tumor cell in an acidic microenvironment, the method comprising the steps of:
(a) contacting the composition of claim 1 with a surface of a tumor cell;
(b) adsorbing the composition comprising fluorescent noble metal nanoparticles on to the surface of the tumor cell; and
(c) detecting the presence of the fluorescent nanoparticle on the surface of the tumor cell.

7. The composition of claim 5 , wherein the pHLIP comprises the sequence of SEQ ID NO: 1.

8. The composition of claim 1 , wherein the acidic tumor microenvironment defined by a pH of between 5.3 and 6.5.

9. The method of claim 6 , wherein the acidic tumor microenvironment defined by a pH of between 5.3 and 6.5.

10. The composition of claim 1 , wherein the noble metal nanoparticle has a diameter of 0.3 nm to 3.0 nm.

11. The method of claim 6 , wherein the noble metal nanoparticle has a diameter of 0. 3 nm to 3.0 nm.

12. The method of claim 6 , wherein the noble metal nanoparticle comprises between 2 and 1000 noble metal atoms.

13. The method of claim 6 , wherein the noble metal is selected from the group consisting of gold, silver, and copper.

14. The method of claim 6 , wherein the nanoparticle further comprises a pH-dependent peptide.

15. The method of claim 14 , wherein the pH-dependent peptide comprises pH low insertion peptide (pHLIP).

16. The method of claim 15 , wherein the pHLIP comprises the sequence of SEQ ID NO: 1.

Assignees

• Zheng Jie
• Yu Mengxiao
• Univ Texas

Inventors

• Zheng Jie
• Yu Mengxiao

Classifications

• Y10S977/773

  Nanoparticle, i.e. structure having three dimensions of 100 nm or less · CPC title

• G01N33/587 Primary

  Nanoparticles · CPC title

• Y10S977/92

  Detection of biochemical · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• A61K49/0065

  the luminescent/fluorescent agent having itself a special physical form, e.g. gold nanoparticle · CPC title