NIR-II imaging probe and methods of using the NIR-II imaging probe for dynamic in vivo tracking

Patent metadata

Field	Value
Publication number	US-11951187-B2
Application number	US-202117179948-A
Country	US
Kind code	B2
Filing date	Feb 19, 2021
Priority date	Feb 19, 2020
Publication date	Apr 9, 2024
Grant date	Apr 9, 2024

Abstract

The disclosure provides NIR-II imaging probes and methods of using the NIR-II imaging probes for dynamic in vivo tracking of cells, such as stem cells, or other substances. NIR-II imaging probes can include a biocompatible NIR-II dye molecule coupled to an organic, biocompatible protein carrier complex, including a carrier protein coupled to a cell-penetrating peptide.

First claim

The invention claimed is:

1. An NIR-II optical imaging probe comprising:
a biocompatible NIR-II dye molecule coupled to an organic, biocompatible protein carrier complex, the protein carrier complex comprising a carrier protein coupled to a cell-penetrating peptide (CPP),
wherein the probe emits detectable NIR-II fluorescence and wherein the molar ratio of the NIR-II dye molecule to carrier protein to CPP is from about 0.5-1.5 NIR-II dye molecule to 0.5-1.5 carrier protein to 0.5-1.5 CPP.

2. The NIR-II optical imaging probe of claim 1 , wherein the carrier protein comprises a serum albumin protein.

3. The NIR-II optical imaging probe of claim 2 , wherein the serum albumin protein is selected from human serum albumin (HSA) molecule and bovine serum albumin (BSA) molecule.

4. The NIR-II optical imaging probe of claim 1 , wherein the CPP comprises trans-activator of transcription (Tat) peptide of HIV, or a derivative or segment thereof retaining cell membrane penetrating functionality.

5. The NIR-II optical imaging probe of claim 4 , wherein the Tat peptide comprises a peptide sequence having at least 75% sequence identity with SEQ ID NO: 1.

6. The NIR-II optical imaging probe of claim 1 , wherein the biocompatible NIR-II dye molecule is selected from the group consisting of: CH-4T, CH1055, carboxyl NIR-II dye molecules, NIR-II cyanine dye molecules, and combinations thereof.

7. The NIR-II optical imaging probe of claim 6 , wherein the biocompatible NIR-II dye molecule is CH-4T.

8. The NIR-II optical imaging probe of claim 1 , wherein the carrier protein is coupled to the CPP through a carbodiimide-mediated coupling reaction.

9. The NIR-II optical imaging probe of claim 1 , wherein the molar ratio of the NIR-II dye molecule to carrier protein to CPP is about 1 NIR-II dye molecule to 1 carrier protein to 1 CPP.

10. A cell including at least one NIR-II optical imaging probe of claim 1 .

11. The cell of claim 10 , wherein the cell is selected from the group consisting of: a stem cell, a pluripotent cell, an immune cell, a donor cell, and a cancer cell.

12. The cell of claim 10 , wherein the cell is a human stem cell.

13. A pharmaceutically acceptable imaging composition comprising:
a plurality of NIR-II optical imaging probes of claim 1 or a plurality of target cells, wherein at least a portion of the target cells each include one or more of the NIR-II optical imaging probes of claim 1 ; and
a pharmaceutically acceptable carrier.

14. The pharmaceutically acceptable imaging composition of claim 13 , wherein the composition comprises a plurality of target cells, wherein at least a portion of the target cells each include one or more of the NIR-II optical imaging probes of claim 1 and wherein the cells are selected from the group consisting of: stem cells, immune cells, and donor cells.

15. An imaging kit comprising:
the pharmaceutically acceptable imaging composition of claim 13 , and
instructions for administration of the pharmaceutically acceptable imaging composition to a patient and imaging of the patient.

Assignees

• Univ Leland Stanford Junior
• The Board Of Trustees Of Leland Stanford Junior Univ

Inventors

• Cheng Zhen
• Chen Hao

Classifications

• A61K49/0056 Primary

  Peptides, proteins, polyamino acids · CPC title

• A61K49/0021 Primary

  the fluorescent group being a small organic molecule · CPC title

• A61K49/0097

  Cells, viruses, ghosts, red blood cells, viral vectors, used for imaging or diagnosis in vivo · CPC title