US 12,440,582 B2
Biothiol-activatable probe and method of use
Jie Zheng, Plano, TX (US); and Xingya Jiang, Richardson, TX (US)
Assigned to BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM, Austin, TX (US)
Appl. No. 17/620,312
Filed by BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM, Austin, TX (US)
PCT Filed Jun. 17, 2020, PCT No. PCT/US2020/038045
§ 371(c)(1), (2) Date Dec. 17, 2021,
PCT Pub. No. WO2020/257224, PCT Pub. Date Dec. 24, 2020.
Claims priority of provisional application 62/862,484, filed on Jun. 17, 2019.
Prior Publication US 2022/0241439 A1, Aug. 4, 2022
Int. Cl. A61K 49/00 (2006.01); A61K 9/51 (2006.01); A61K 49/18 (2006.01); A61P 1/16 (2006.01); G01N 33/542 (2006.01); G01N 33/543 (2006.01); G01N 33/68 (2006.01); B82Y 5/00 (2011.01)
CPC A61K 49/0093 (2013.01) [A61K 9/5115 (2013.01); A61K 49/0034 (2013.01); A61K 49/186 (2013.01); A61P 1/16 (2018.01); G01N 33/542 (2013.01); G01N 33/54353 (2013.01); G01N 33/6815 (2013.01); B82Y 5/00 (2013.01); G01N 2800/085 (2013.01)] 21 Claims
 
1. A biothiol-activatable composition which dissociates in the presence of a concentration of biothiols in a liver of a living subject, the biothiol-activatable composition comprising:
a metal nanoparticle;
a protein-binding reporter molecule, wherein the protein-binding reporter molecule is indocyanine green (ICG); and
a linker molecule that is conjugated to the metal nanoparticle and further conjugated to the reporter molecule, wherein the linker molecule comprises glutathione, oxidized glutathione, thiolated polyethylene glycol, or disulfide polyethylene glycol;
wherein the protein-binding reporter molecule is configured to bind serum protein;
wherein the metal nanoparticle has an average number of ICG molecules conjugated thereto, and the average number of ICG molecules conjugated to the metal nanoparticle is 1 to 4; and
wherein the linker molecule is displaceable or cleavable in the liver in the presence of a concentration of biothiols that are produced by the liver, such that the protein-binding reporter molecule and the metal nanoparticle are released from each other in the presence of the concentration of biothiols that are produced by the liver, and the metal nanoparticle is configured to be excreted by the kidneys into the urine upon release.