Virion-derived nanospheres for selective delivery of therapeutic and diagnostic agents to cancer cells
The invention relates to methods for producing papilloma-derived nanosphere particles that contain therapeutic, diagnostic, or other agents. The invention also provides nanosphere particle preparations that are useful for selectively delivering therapeutic, diagnostic, and/or other agents to cancer cells of subjects without eliciting a serotype-specific immunogenic response in the subjects.
1. A papillomavirus L1 capsid protein encoded by the nucleic acid sequence of SEQ ID NO: 1.
2. A nanosphere particle comprising the papillomavirus L1 capsid protein of claim 1 .
3. The nanosphere particle of claim 2 further comprising a papillomavirus L2 capsid protein.
4. The nanosphere particle of claim 2 , wherein an agent is attached to a surface of the nanosphere particle.
5. The nanosphere particle of claim 3 , wherein the agent is covalently attached to a surface of the nanosphere particle.
6. The nanosphere particle of claim 3 , wherein the agent comprises an anti-cancer agent.
7. The nanosphere particle of claim 3 , wherein the agent comprises a toxic agent.
8. The nanosphere particle of claim 3 , wherein the agent comprises a dye.
9. The nanosphere particle of claim 8 , wherein the dye comprises a fluorescent dye.
10. The nanosphere particle of claim 3 , wherein the agent is a therapeutic agent.
11. The nanosphere particle of claim 3 , wherein the agent is a diagnostic agent.
12. The nanosphere particle of claim 2 further comprising a papillomavirus L2 capsid protein.
13. A nanosphere particle comprising:
a papillomavirus L1 capsid protein encoded by the nucleic acid sequence of SEQ ID NO: 1; and
a papillomavirus L2 capsid protein,
wherein a dye is attached to a surface of the nanosphere particle.
14. The nanosphere particle of claim 13 , wherein the dye is covalently attached to a surface of the nanosphere particle.
15. A method comprising delivering to a subject having a tumor the nanosphere particle of claim 2 .
16. The method of claim 15 , wherein the tumor is pre-malignant, malignant, or metastatic.
17. A method comprising injecting into a tumor of a subject the nanosphere particle of claim 2 .
18. The method of claim 17 , wherein the tumor is pre-malignant, malignant, or metastatic.
19. A cultured mammalian cell expressing the papillomavirus L1 capsid protein of claim 1 .
20. The cultured mammalian cell of claim 19 , wherein the cultured mammalian cell is a cultured human embryonic kidney (HEK) cell.
21. The cultured mammalian cell of claim 20 , wherein the cultured HEK cell is a cultured 293 HEK cell.
22. A nucleic acid of SEQ ID NO: 1 that encodes a papillomavirus L1 protein.
23. A cultured mammalian cell expressing the nucleic acid of claim 22 .
24. The cultured mammalian cell of claim 23 , wherein the cultured mammalian cell is a cultured human embryonic kidney (HEK) cell.
25. The cultured mammalian cell of claim 24 , wherein the cultured HEK cell is a cultured 293 HEK cell.
26. A method of producing a nanosphere particle, comprising expressing in a mammalian cell in culture media the nucleic acid of claim 22 , and collecting a self-assembled nanosphere particle comprising a papillomavirus L1 protein encoded by the nucleic acid.
27. The method of claim 26 further comprising expressing in the mammalian cell a nucleic acid encoding a papillomavirus L2 protein.
28. The method of claim 26 further comprising attaching an agent to a surface of the nanosphere particle.
29. The method of claim 28 , wherein the agent comprises a dye.
30. The method of claim 29 , wherein the dye is a fluorescent dye.