Ultrasmall nanoparticles labeled with Zirconium-89 and methods thereof
Described herein are nanoprobes comprising ultrasmall aminated and cRGDY-conjugated nanoparticles labeled with Zirconium-89 ( 89 Zr) 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.
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.