Self-assembling complex for targeting chemical agents to cells
The present invention relates to a complex that can be injected into the body to hone in on target cells to deliver molecules. In one embodiment, the invention provides a drug delivery system that includes components that self-assemble into one targeted conjugate. In another embodiment, the invention includes a targeted carrier protein and a nucleic acid sequence non-covalently linked to one or more drugs.
1. A method of preparing a drug delivery molecule, comprising:
incubating an intercalating drug with a nucleic acid molecule to create a complex; and
incubating said complex with a polypeptide adapted to target and penetrate a type of cell to form the drug delivery molecule.
2. The method of claim 1 , wherein the intercalating drug is doxorubicin.
3. The method of claim 1 , wherein the nucleic acid molecule is double-stranded.
4. The method of claim 1 , wherein the polypeptide comprises a receptor binding domain of heregulin-α.
5. The method of claim 1 , wherein the polypeptide comprises an endosomolytic domain.
6. The method of claim 1 , wherein the polypeptide comprises a polylysine motif.
7. The method of claim 6 , wherein the polylysine motif is a decalysine.
8. The method of claim 1 , wherein the nucleic acid molecule comprises a sequence according to SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or a combination thereof.
9. The method of claim 1 , wherein the intercalating drug is a chemotherapeutic agent.
10. The method of claim 1 , wherein the polypeptide comprises a targeting ligand, an endosomolytic domain, and a polylysine motif.
11. The method of claim 1 , wherein the type of cell is a breast cancer cell.
12. The method of claim 1 , wherein the type of cell is a HER2+ breast cancer cell.
13. The method of claim 1 , wherein the type of cell is a glioma cell.
14. The method of claim 1 , wherein the polypeptide comprises a penton base segment.
15. The method of claim 14 , wherein the polypeptide comprises a receptor binding domain of heregulin-α.
16. The method of claim 14 , wherein the polypeptide further comprises a polylysine motif.
17. The method of claim 16 , wherein the polylysine motif is a decalysine.
18. The method of claim 15 , wherein the polypeptide further comprises a polylysine motif.
19. The method of claim 18 , wherein the polylysine motif is a decalysine.
20. The method of claim 1 , wherein the polypeptide comprises HerPBK10.
21. The method of claim 20 , wherein the nucleic acid molecule is a double stranded nucleic acid sequence comprising a first nucleic acid molecule having a sequence according to SEQ ID NO: 6, and a second nucleic acid molecule having a sequence according to SEQ ID NO: 7.
22. The method of claim 21 , wherein the intercalating drug is doxorubicin.
23. The method of claim 1 , comprising separating unbound intercalating drug from the complex.
24. The method of claim 23 , wherein the unbound intercalating drug is separated from the complex by ultrafiltration centrifugation.
25. The method of claim 1 , comprising separating unbound complex from the drug delivery molecule.
26. The method of claim 25 , wherein the complex is separated from the drug delivery molecule by size exclusion chromatography.