Methods and compositions related to targeting tumors and wounds
View Patent ↗Disclosed are compositions and methods useful for targeting tumors, sites of injury and blood clots. The compositions and methods are based on peptide sequences that selectively bind to and home to tumors, sites of injury and blood clots in animals. The disclosed targeting is useful for delivering therapeutic and detectable agents to tumors, sites of injury and blood clots.
1. An isolated peptide comprising an amino acid segment comprising the amino acid sequence of SEQ ID NO: 1, an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 1, or the amino acid sequence of SEQ ID NO: 1 having one, two, or three conservative amino acid substitutions, wherein the peptide has a length of less than 100 residues, wherein the amino acid segment is circular.
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 comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 1.
6. The isolated peptide of claim 1 , wherein the amino acid segment comprises the amino acid sequence of SEQ ID NO:1.
7. The isolated peptide of claim 1 , wherein the amino acid sequence of SEQ ID NO:1 has one, two, or three conservative amino acid substitutions.
8. The isolated peptide of claim 1 , wherein the amino acid segment is circularized via a disulfide bond.
9. The isolated peptide of claim 1 , wherein the peptide selectively homes to tumors and sites of injury.
10. The isolated peptide of claim 1 , wherein the amino acid segment consists of the amino acid sequence of SEQ ID NO:1 having no, one, two, or three conservative amino acid substitutions.
11. The isolated peptide of claim 1 , wherein the amino acid segment comprises the amino acid sequence of SEQ ID NO:1 having one or two conservative amino acid substitutions.
12. The isolated peptide of claim 1 , wherein the amino acid segment comprises the amino acid sequence of SEQ ID NO:1 having one conservative amino acid substitution.
13. The isolated peptide of claim 1 , wherein the amino acid segment consists of the amino acid sequence of SEQ ID NO:1.
14. A conjugate, wherein the conjugate comprises a moiety linked to the peptide of claim 1 .
15. The conjugate of claim 14 , wherein the peptide selectively interacts with tumors and sites of injury.
16. The conjugate of claim 14 , wherein the moiety is a cancer chemotherapeutic agent, a cytotoxic agent, an anti-angiogenic agent, 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 thereof.
17. The conjugate of claim 14 , wherein the moiety is a therapeutic agent.
18. The conjugate of claim 14 , wherein the moiety is a detectable agent.
19. The moiety of claim 14 , wherein the conjugate comprises a virus.
20. The moiety of claim 19 , wherein the conjugate comprises a phage.
21. The conjugate of claim 14 further comprising a second peptide, wherein the second peptide is a peptide comprising an amino acid segment comprising the amino acid sequence of SEQ ID NO: 1, an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO:1, or the amino acid sequence of SEQ ID NO:1 having one, two, or three conservative amino acid substitutions.
22. A method of directing a moiety to tumors, sites of injury, or sites of blood clots in a subject, comprising administering to the subject a conjugate comprising a moiety linked to a peptide, wherein the peptide comprises an amino acid segment comprising the amino acid sequence of SEQ ID NO: 1, an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 1, or the amino acid sequence of SEQ ID NO: 1 having one, two, or three conservative amino acid substitutions, wherein the conjugate binds to fibrin, clotted fibronectin, or clotted plasma protein.
23. The method of claim 22 , wherein the subject has cancer, and wherein the moiety is directed to tumor stroma in the subject.
24. The method of claim 23 , wherein the moiety is a therapeutic agent and wherein the conjugate treats the cancer.
25. The method of claim 23 , wherein the moiety is a therapeutic agent and wherein the conjugate has a therapeutic effect on the cancer.
26. The method of claim 23 , wherein the moiety is a therapeutic agent and wherein the size of a tumor is reduced.
27. The method of claim 23 , wherein the moiety is a therapeutic agent and wherein the growth of a tumor is reduced.
28. The method of claim 23 , wherein the moiety is used to detect the cancer, visualize one or more tumors, or both.
29. The method of claim 23 , wherein the moiety is a cancer therapeutic agent and wherein the conjugate treats the cancer.
30. The method of claim 23 , wherein the moiety is a cancer therapeutic agent and wherein the conjugate has a therapeutic effect on the cancer.
31. The method of claim 23 , wherein the moiety is a cancer therapeutic agent and wherein the size of a tumor is reduced.
32. The method of claim 23 , wherein the moiety is a cancer therapeutic agent and wherein the growth of a tumor is reduced.