Virion-derived nanospheres for selective delivery of therapeutic and diagnostic agents to cancer cells
View Patent ↗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 nanosphere particle comprising:
papillomavirus L1 capsid proteins encoded by the nucleic acid sequence of SEQ ID NO: 2; and
a therapeutic agent attached to a surface of the nanosphere particle.
2. The nanosphere particle of claim 1 , wherein the therapeutic agent is a dye.
3. The nanosphere particle of claim 1 , wherein the therapeutic agent is an anticancer agent.
4. The nanosphere particle of claim 1 , wherein the therapeutic agent is a toxic agent.
5. The nanosphere particle of claim 1 further comprising papillomavirus L2 capsid proteins.
6. The nanosphere particle of claim 1 , wherein the modified papillomavirus L1 capsid proteins have at least one amino acid that is PEGylated.
7. The nanosphere particle of claim 1 , wherein the nanosphere particle is assembled in vitro from a plurality of modified papillomavirus L1 capsid proteins encoded by the nucleic acid sequence of SEQ ID NO: 2.
8. The nanosphere particle of claim 1 , wherein the therapeutic agent is covalently attached to a surface of the nanosphere particle.
9. The nanosphere particle of claim 1 , wherein the L1 capsid is isolated from bacterial cells, yeast cells, insect cells, plant cells, or mammalian cells.
10. The nanosphere particle of claim 9 , wherein the L1 capsid is isolated from mammalian cells.
11. The nanosphere particle of claim 10 , wherein the mammalian cells are human embryonic kidney cells.
12. A method comprising delivering to a subject having a tumor the nanosphere particle of claim 1 .
13. A method comprising injecting into a tumor of a subject the nanosphere particle of claim 1 .
14. The nanosphere particle of claim 1 further comprising papillomavirus L2 capsid proteins, wherein the therapeutic agent is an anti-cancer agent.
15. The nanosphere particle of claim 14 , wherein the anti-cancer agent is covalently attached to a surface of the nanosphere particle.
16. A method comprising delivering to a subject having a tumor the nanosphere particle of claim 14 .
17. A method comprising injecting into a tumor of a subject the nanosphere particle of claim 14 .
18. The nanosphere particle of claim 1 further comprising papillomavirus L2 capsid proteins, wherein the therapeutic agent is a toxic agent.
19. The nanosphere particle of claim 18 , wherein the toxic agent is covalently attached to a surface of the nanosphere particle.
20. A method comprising delivering to a subject having a tumor the nanosphere particle of claim 18 .
21. A method comprising injecting into a tumor of a subject the nanosphere particle of claim 18 .
22. A nanosphere particle comprising:
a papillomavirus L1 capsid protein encoded by the nucleic acid sequence of SEQ ID NO: 2;
papillomavirus L2 capsid proteins; and
a dye attached to a surface of the nanosphere particle.
23. The nanosphere particle of claim 22 , wherein the dye is covalently attached to a surface of the nanosphere particle.
24. A method comprising delivering to a subject having a tumor the nanosphere particle of claim 22 .
25. A method comprising injecting into a tumor of a subject the nanosphere particle of claim 22 .
26. A method comprising expressing in mammalian cells a nucleic acid comprising the sequence of SEQ ID NO: 2, and isolating from the mammalian cells L1 capsid protein encoded by the nucleic acid.
27. The method of claim 26 , wherein the mammalian cells are human embryonic kidney (HEK) cells.
28. The method of claim 27 , wherein the HEK cells are 293 cells.
29. A cultured mammalian cell comprising a nucleic acid comprising the sequence of SEQ ID NO: 2.
30. The cultured mammalian cell of claim 29 , wherein the cultured mammalian cell is a cultured human embryonic kidney (HEK) cell.
31. The mammalian cell of claim 30 , wherein the cultured HEK cell is a cultured 293 HEK cell.