Compositions and methods for inhibiting the biological activity of soluble biomolecules
The disclosure provides, among other things, compositions that bind to and inhibit the biological activity of soluble biomolecules, as well as pharmaceutical compositions thereof. Also provided herein are a number of applications (e.g., therapeutic applications) in which the compositions are useful.
1. A particle having at least one surface, and an agent immobilized on the surface, wherein:
the agent selectively binds to a target that is a first member of a specific binding pair;
binding of the target to the particle inhibits the interaction of the target with a second member of the specific binding pair;
the target is a ligand of a cell surface receptor protein;
the agent is disposed on a surface of the particle such that it has a reduced ability to interact with a molecule on the surface of a cell; and
the particle is shaped and sized to circulate in the vasculature of a subject.
2. The particle of claim 1 , wherein the agent is sterically inhibited from interacting with a molecule on the surface of a cell.
3. The particle of claim 1 , wherein the cell surface receptor protein is expressed by a cancer cell.
4. The particle of claim 1 , wherein the cell surface receptor protein is a protein shed by the cancer cell as a soluble form of the cell surface receptor protein.
5. The particle of claim 1 , wherein the cell surface receptor protein, when activated, induces apoptosis.
6. The particle of claim 1 , wherein the target is a native ligand of a cell surface receptor protein.
7. The particle of claim 1 , wherein the target is a non-native ligand of a cell surface receptor protein.
8. The particle of claim 7 , wherein the non-native ligand of a cell surface receptor protein is a drug.
9. The particle of claim 1 , wherein the target is a cytokine, chemokine or enzyme.
10. The particle of claim 9 , wherein the cytokine, chemokine or enzyme is expressed by a cancer cell.
11. The particle of claim 1 , wherein the ligand is an interleukin protein.
12. The particle of claim 1 , wherein the ligand is a tumor necrosis factor (TNF) family ligand.
13. The particle of claim 12 , wherein the TNF family ligand is TNF-α.
14. The particle of claim 1 , wherein the target is selected from interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), TNF-β, Fas ligand, lymphotoxin, lymphotoxin alpha, lymphotoxin beta, 4-1BB ligand, CD30 ligand, EDA-A1, LIGHT, TLA1, TWEAK, and TRAIL.
15. The particle of claim 1 , wherein the agent is a small molecule, a macrocycle compound, a polypeptide, a protein, a peptide, a peptidomimetic compound, an aptamer, a nucleic acid, or a nucleic acid analog.
16. The particle of claim 1 , wherein the diameter of the particle is no greater than 250 nm.
17. The particle of claim 1 , further comprising a coating, and wherein the coating inhibits interactions between the agent and a molecule on the surface of a cell.
18. The particle of claim 17 , wherein the coating comprises a plurality of coating moieties or coating molecules.
19. The particle of claim 18 , wherein the at least one molecule of the plurality of coating molecules or at least one moiety of the plurality of coating moieties is bound to the surface of the particle.
20. The particle of claim 18 , wherein the plurality of coating moieties or coating molecules comprises a polymer.
21. The particle of claim 20 , wherein the polymer is selected from polyethylene glycol (PEG), a poly(amino acid), polylactate, polylactic acid, a sugar, a lipid, polyglutamic acid, polyglycolic acid (PGA), polylactic acid (PLA), poly(lactic-co-glycolic acid) (PLGA), polyvinyl acetate (PVA), poly(ethylene glycol-b-(DL-lactic acid-co-glycolic acid)-b-ethylene glycol) (PEG-PLGA-PEG), polycaprolactone-PEG (PCL-PEG), poly(vinylidene fluoride)-PEG (PVDF-PEG), poly(lactic acid-co-PEG) (PLA-PEG), poly(methyl methacrylate)-PEG (PMMA-PEG), and a combination thereof.
22. The particle of claim 20 , wherein the polymer is biodegradable.