Ultrasmall nanoparticles labeled with Zirconium-89 and methods thereof

Patent metadata

Field	Value
Publication number	US-11559591-B2
Application number	US-201816616368-A
Country	US
Kind code	B2
Filing date	May 17, 2018
Priority date	May 25, 2017
Publication date	Jan 24, 2023
Grant date	Jan 24, 2023

Abstract

Described herein are nanoprobes comprising ultrasmall aminated and cRGDY-conjugated nanoparticles labeled with Zirconium-89 (89Zr) and methods of their use. The provided compositions are renally clearable and possess suitable blood circulation half-time, high tumor active targeting capability, dominant renal clearance, low liver accumulation, and a high tumor-to-background ratio. The described nanoprobes exhibit great potential as “target-or-clear” tracers to human subjects for systemic targeted imaging (or treatment) of cancer.

First claim

What is claimed is:

1. A nanoprobe created from an aminated nanoparticle, the nanoprobe comprising:
a silica nanoparticle that comprises a polyethylene glycol (PEG) layer;
a targeting agent conjugated to the silica nanoparticle via an amine group underneath the PEG layer; and
a radiolabel conjugated to the silica nanoparticle via another amine group underneath the PEG layer,
wherein the silica nanoparticle has a diameter no greater than 20 nanometers.

2. The nanoprobe of claim 1 , wherein the radiolabel comprises 89Zr.

3. The nanoprobe of claim 1 , wherein the targeting agent comprises a targeting peptide.

4. The nanoprobe of claim 3 , wherein the targeting peptide comprises a member selected from the group consisting of arginylglycylaspartic acid (RGD), cyclic arginylglycylaspartic acid (cRGD), an analog of RGD, alpha-Melanocyte-stimulating hormone (alphaMSH), and any peptide known to be immunomodulatory and anti-inflammatory in nature.

5. The nanoprobe of claim 1 , wherein the targeting agent comprises an antibody fragment, and wherein the antibody fragment is in a range from about 5 kDa to about 25 kDa.

6. The nanoprobe of claim 1 , wherein the targeting agent comprises an antibody fragment, and wherein the antibody fragment is from about 20 kDa to about 45 kDa.

7. The nanoprobe of claim 1 , wherein the targeting agent comprises an antibody fragment, and wherein the antibody fragment is from about 40 kDa to about 80 kDa.

8. The nanoprobe of claim 1 , wherein the silica nanoparticle comprises a silica-based core and a silica shell surrounding at least a portion of the silica-based core.

9. The nanoprobe of claim 1 , wherein the silica nanoparticle comprises a silica-based core and a fluorescent compound within the silica-based core.

10. The nanoprobe of claim 1 , wherein the targeting agent comprises VEGF 121 .

11. The nanoprobe of claim 1 , wherein the targeting agent comprises an antibody fragment selected from the set consisting of a Fab fragment, a single chain variable fragment (scFv), and a single domain antibody (sdAb) fragment.

12. The nanoprobe of claim 11 , wherein the antibody fragment is a single chain variable fragment (scFv).

13. The nanoprobe of claim 11 , wherein the antibody fragment is a single domain antibody (sdAb) fragment.

14. The nanoprobe of claim 1 , wherein from one to ten targeting agents are conjugated to the silica nanoparticle via amine groups.

15. The nanoprobe of claim 1 , wherein the silica nanoparticle has a diameter no greater than 15 nanometers.

16. The nanoprobe of claim 1 , wherein the silica nanoparticle has a diameter in a range from 1 nm to 20 nm.

17. The nanoprobe of claim 1 , wherein the targeting agent comprises a member selected from the set consisting of anti-CEA scFv, anti-GPIIb/IIIa, anti-VEGF-A, anti-VEGF-R, and anti-TNF-α.

18. The nanoprobe of claim 1 , wherein the nanoprobe further comprises one or more imaging agents.

19. The nanoprobe of claim 18 , wherein the one or more imaging agents comprise a PET or SPECT tracer.

20. The nanoprobe of claim 19 , wherein the PET or SPECT tracer comprises a member selected from the group consisting of 89 Zr, 64 Cu, 18 F fluorodeoxyglucose, 177 Lu, 225 At, and 90 Y.

21. The nanoprobe of claim 1 , further comprising a therapeutic agent.

22. The nanoprobe of claim 1 , wherein the targeting agent comprises a recombinant antibody fragment.

Assignees

• Memorial Sloan Kettering Cancer Center
• Univ Cornell

Inventors

• Bradbury Michelle S
• Chen Feng
• Wiesner Ulrich
• Ma Kai

Classifications

• B82Y15/00

  Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors · CPC title

• A61K51/10

  Antibodies or immunoglobulins; Fragments thereof {, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody} · CPC title

• A61K51/082

  the peptide being a RGD-containing peptide · CPC title

• A61K51/0482

  chelates from cyclic ligands, e.g. DOTA · CPC title

• A61K49/0093

  Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle · CPC title