Targeted carrier fusions for delivery of chemotherapeutic agents
The present invention provides for fusion proteins that act as targeted drug carries. The proteins are derived from molecules that possess natural drug-binding capabilities that are further engineered to target specific cell types, and optionally to have altered/improved drug binding characteristics. These fusion proteins are useful in, for example, delivery of chemotherapeutic compounds to cancer cells.
1. A fusion protein comprising a drug-binding portion of a naturally-occurring carrier polypeptide and a cancer cell- or tumor vasculature-targeting peptide, wherein said carrier polypeptide is an apoprotein or a binding protein.
2. The fusion protein of claim 1 , wherein said apoprotein is CagA or NscA.
3. The fusion protein of claim 1 , wherein said binding protein is a biosynthetic gene cluster protein or a pathogen drug-resistance protein.
4. The fusion protein of claim 3 , wherein said biosynthetic gene cluster protein is BlmA, PlmA or MRD.
5. The fusion protein of claim 1 , wherein said cancer cell is a pancreatic cancer cell, a liver cancer cell, a lymphoma cell, a myeloma cell, a neuroblastoma cell, a breast cancer cell, a prostate cancer, or a head and neck cancer cell.
6. The fusion protein of claim 1 , further comprising a drug complexed with said fusion protein.
7. The fusion protein of claim 6 , wherein said drug is selected from the group consisting of an antibiotic, a plant akyloid, an alkylating agent, a DNA repair inhibitor or a DNA cleaving agent.
8. The fusion protein of claim 6 , wherein said DNA cleaving agent is an enediyne.
9. The fusion protein of claim 1 , wherein said first cell-targeting peptide is attached at the N-terminus of said carrier polypeptide.
10. The fusion protein of claim 1 , wherein said first cell-targeting peptide is attached at the C-terminus of said carrier polypeptide.
11. The fusion protein of claim 1 , wherein said first cell-targeting peptide is inserted as a continuous segment into said carrier polypeptide.
12. The fusion protein of claim 1 , wherein said fusion protein comprises multiple copies of said cell-targeting peptide.
13. The fusion protein of claim 1 , further comprising a second cell-targeting peptide.
14. The fusion protein of claim 1 , wherein said tumor vasculature-targeting peptide is derived from pancreatic cancer, liver cancer, lymphoma, myeloma, neuroblastoma, breast cancer, prostate cancer or head and neck cancer.