Methods and compositions related to internalizing RGD peptides
Disclosed are compositions and methods useful for targeting tissue undergoing angiogenesis or to cells or tissue expressing αv integrins. The compositions and methods are based on peptide sequences that selectively bind to and home to tissue undergoing angiogenesis or to cells or tissue expressing αv integrins in animals. The disclosed targeting is useful for delivering therapeutic and detectable agents to tissue experiencing angiogenesis or to cells or tissue expressing αv integrins.
1. An isolated peptide comprising an amino acid segment comprising the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO:290, one of the amino acid sequences CRGD(R/K/H)GV(D/E/H)C (SEQ ID NO:329), or one of the amino acid sequences CRGDHGP(D/E/H)C (SEQ ID NO:330).
2. The isolated peptide of claim 1 , wherein the peptide has a length of less than 100 residues.
3. The isolated peptide of claim 1 , wherein the peptide has a length of less than 50 residues.
4. The isolated peptide of claim 1 , wherein the peptide has a length of less than 20 residues.
5. The isolated peptide of claim 1 , wherein the amino acid segment is cyclic.
6. The isolated peptide of claim 5 , wherein the amino acid segment is cyclized via a disulfide bond.
7. The isolated peptide of claim 1 , wherein the peptide selectively homes to a site of angiogenesis.
8. The isolated peptide of claim 7 , wherein the angiogenesis is at a site of injury.
9. The isolated peptide of claim 7 , wherein the angiogenesis is at a surgical site.
10. The isolated peptide of claim 1 , wherein the peptide selectively homes to a tumor.
11. The isolated peptide of claim 1 , wherein the peptide selectively homes to a site of arthritis.
12. The isolated peptide of claim 1 , wherein the peptide selectively homes to a cell or tissue expressing one or more αv integrins.
13. The isolated peptide of claim 1 , wherein the peptide selectively homes to a cell or tissue expressing one or more αv integrins and neuropilin-1.
14. The isolated peptide of claim 1 , wherein the peptide consists of the amino acid segment.
15. A conjugate, wherein the conjugate comprises a moiety linked to the peptide of claim 1 .
16. The conjugate of claim 15 , wherein the moiety is a an anti-angiogenic agent, a pro-angiogenic agent, a cancer chemotherapeutic agent, a cytotoxic agent, an anti-inflammatory agent, an anti-arthritic agent, a nanoparticle, a polypeptide, a nucleic acid molecule, a small molecule, a fluorophore, fluorescein, rhodamine, a radionuclide, indium-111, technetium-99, carbon-11, carbon-13, or a combination.
17. The conjugate of claim 16 , wherein the moiety is a therapeutic agent.
18. The conjugate of claim 17 , wherein the therapeutic agent is decorin.
19. The conjugate of claim 16 , wherein the moiety is a detectable agent.
20. The conjugate of claim 16 , wherein the conjugate comprises a virus.
21. The conjugate of claim 20 , wherein the conjugate comprises a phage.