Thermally-targeted delivery of medicaments including doxorubicin
View Patent ↗Elastin-like polypeptide (ELP) serves as a vector for thermally-targeted delivery of therapeutics, including cytotoxic chemotherapeutic drugs such as doxorubicin. Examples of an ELP-based delivery vehicle can comprise: (1) a cell penetrating peptide, such as a Tat peptide, (2) ELP, and (3) the lysosomally degradable glycylphenylalanylleucylglycine (GFLG) (SEQ ID NO: 3) spacer and a cysteine residue (SEQ ID NO: 4) conjugated to therapeutic such as doxorubicin, or an analog thereof.
1. A composition, comprising an ELP-containing protein, a GFLG (SEQ ID NO: 3) linker coupled thereto, and a therapeutic agent coupled with the linker, wherein the GFLG (SEQ ID NO: 3) linker comprises a C-terminal cysteine residue coupled to the therapeutic agent.
2. The composition of claim 1 , wherein ELP is a five amino acid repeat comprising the sequence XGVPG (SEQ ID NO: 1), wherein X is any amino acid except proline.
3. The composition of claim 1 , wherein the therapeutic agent is a chemotherapeutic agent.
4. The composition of claim 3 , wherein the chemotherapeutic agent is doxorubicin.
5. The composition of claim 3 , wherein the chemotherapeutic agent is methotrexate, vinblastin, or paclitaxel.
6. The composition of claim 1 , comprising a cell-penetrating peptide sequence coupled with the ELP.
7. The composition of claim 6 , wherein the cell-penetrating peptide sequence is a Tat peptide.
8. The composition of claim 6 , wherein the cell-penetrating peptide is selected from Antp, Tat, MTS, Bac-7, Trans, and pVEC.
9. The composition of claim 1 , which is Tat-ELP-GFLGC (SEQ ID NO: 4)—therapeutic agent.
10. The composition of claim 9 , wherein the therapeutic agent is Dox.
11. The composition of claim 1 , with a phase transition of about 39° C. to about 42° C.
12. A method of delivering a therapeutic agent to a tumor, comprising the steps of: administering a composition of claim 1 ; and applying local hyperthermia to the tumor site.
13. A method of treating, preventing, or managing cancer, comprising: administering a composition of claim 1 ; and applying local hyperthermia to a tumor site.
14. The method of claim 12 or claim 13 , wherein the tumor is a breast tumor, lung tumor, colon cancer, or melanoma.