EP-4735009-A1 - FERRITIN-GOLD NANOPARTICLE CONJUGATES FOR PHOTODYNAMIC CANCER THERAPY

EP4735009A1EP 4735009 A1EP4735009 A1EP 4735009A1EP-4735009-A1

Abstract

The present invention provides a composition comprising a Ferritin-metal nanoparticle bioconjugate, wherein the Ferritin-metal nanoparticle bioconjugate comprises at least one metal nanoparticle and at least one Ferritin or a variant or a fragment thereof conjugated to the at least one metal nanoparticle; and wherein the Ferritin-metal nanoparticle bioconjugate specifically targets at least one cell expressing a transferrin receptor 1 (TfR1), and methods of making and use thereof.

Inventors

STRONGIN, DANIEL
DUNUWEERA, Shashiprabha Punyakanth
VALENTINE, Ann
CERKEZ, Elizabeth

Assignees

Temple University Of The Commonwealth System Of Higher Education

Dates

Publication Date: 20260506
Application Date: 20240628

Claims (1)

Attorney Docket No.206017-0250-00US CLAIMS What is claimed is: 1. A composition comprising a Ferritin-metal nanoparticle bioconjugate, wherein the Ferritin-metal nanoparticle bioconjugate comprises at least one metal nanoparticle and at least one Ferritin or a variant or a fragment thereof conjugated to the at least one metal nanoparticle; and wherein the Ferritin-metal nanoparticle bioconjugate specifically targets at least one cell expressing a transferrin receptor 1 (TfR1). 2. The composition of claim 1, wherein the at least one Ferritin or a variant or a fragment thereof is selected from the group consisting of a human H-type Ferritin or a variant or a fragment thereof, horse spleen Ferritin or a variant or a fragment thereof, and any combination thereof. 3. The composition of claim 1, wherein the at least one metal nanoparticle is selected from the group consisting of a metal nanorod, metal nanosphere, metal nanostar, and any combination thereof. 4. The composition of claim 1, wherein the at least one metal nanoparticle is selected from the group consisting of a gold nanoparticle, iron nanoparticle, chromium nanoparticle, copper nanoparticle, and any combination thereof. 5. The composition of claim 1, wherein the at least one metal nanoparticle further comprises an oxide coating. 6. The composition of claim 5, wherein the oxide coating is selected from the group consisting of a Fe 2 O 3 coating, SiO 2 coating, and any combination thereof. Attorney Docket No.206017-0250-00US 7. The composition of claim 1, wherein the at least one Ferritin or a variant or a fragment thereof is conjugated to the at least one metal nanoparticle via a linker. 8. The composition of claim 1, wherein the linker comprises N- succinimidyl S-acetylthioacetate or a derivative thereof. 9. The composition of claim 1, wherein the Ferritin-metal nanoparticle bioconjugate has an average hydrodynamic diameter of between 5 nm to 1,000 nm. 10. The composition of claim 9, wherein the Ferritin-metal nanoparticle bioconjugate has an average hydrodynamic diameter of between 10 nm to 300 nm. 11. The composition of claim 1, wherein the Ferritin-metal nanoparticle bioconjugate absorbs light having a wavelength between 200 nm to 1100 nm. 12. The composition of claim 1, wherein the Ferritin-metal nanoparticle bioconjugate releases at least one iron ion when irradiated with light having a wavelength of between 200 nm to 1100 nm. 13. The composition of claim 1, wherein the metal nanoparticle is a gold nanorod, and the Ferritin-metal nanoparticle bioconjugate has an average width of between 5 nm to 20 nm and an average length of between 30 nm to 70 nm. 14. The composition of claim 1, wherein the metal nanoparticle is a gold nanostar, and Attorney Docket No.206017-0250-00US the Ferritin-metal nanoparticle bioconjugate comprises between 3 to 7 spikes, wherein the spikes have an average length of between 20 nm to 150 nm. 15. The composition of claim 1, wherein the metal nanoparticle is a gold nanosphere, and the Ferritin-metal nanoparticle bioconjugate has a surface area of between 50 nm 2 to 900 nm 2 . 16. The composition of claim 1, wherein the Ferritin-metal nanoparticle bioconjugate further comprises a targeting domain. 17. The composition of claim 1, wherein the composition further comprises a therapeutic agent. 18. The composition of claim 1, wherein at least one cell expressing a TfR1 is a cell overexpressing a TfR1. 19. The composition of claim 18, wherein the cell overexpressing a TfR1 is a cancer cell. 20. A method of treating a disease or disorder associated with the level or activity of a TfR1 in a subject in need thereof, wherein the method comprises: administering to the subject the composition of claim 1, and irradiating the subject with light having a wavelength of between 200 nm to 1100 nm. 21. The method of claim 20, wherein the disease or disorder is selected from the group consisting of cancer, prostate cancer, breast cancer, Alzheimer’s disease, and any combination thereof. Attorney Docket No.206017-0250-00US 23. A method of inhibiting proliferation of at least one cell expressing a TfR1, wherein the method comprises: administering to the subject the composition of claim 1, and irradiating the subject with light having a wavelength of between 200 nm to 1100 nm. 24. A method of inducing ferroptosis of at least one cell expressing a TfR1, wherein the method comprises: administering to the subject the composition of claim 1, and irradiating the subject with light having a wavelength of between 200 nm to 1100 nm. 25. The method of claim 24, wherein the irradiation selectively kills or inhibits the at least one cell expressing a TfR1. 26. The method of claim 25, wherein the at least one cell expressing a TfR1 is a cancer cell. 27. A method of making a Ferritin-metal nanoparticle bioconjugate, comprising the steps of: providing a metal nanoparticle; and dispersing the metal nanoparticle in a solution comprising Ferritin. 28. The method of claim 27, wherein the solution comprising Ferritin is a buffered solution.

Description

Attorney Docket No.206017-0250-00US TITLE OF THE INVENTION FERRITIN-GOLD NANOPARTICLE CONJUGATES FOR PHOTODYNAMIC CANCER THERAPY CROSS-REFERENCE TO RELATED APPLICATIONS The present application claims priority to and the benefit of U.S. Provisional Application No.63/510,770, filed June 28, 2023, the disclosure of which is hereby incorporated by reference herein in its entirety. BACKGROUND OF THE INVENTION Ferritin is a protein naturally found in humans and many other life forms. The biological role of the protein is to sequester iron within the protein shell, limiting iron’s interaction with extra and intra-cellular fluid, preventing the toxic formation of reactive oxygen species. Cells, however, need iron for proper function, hence ferritin’s role is to protectively shepherd iron throughout the body within the protein cage and release as necessary. As the metabolic processes of cancer cells are faster than healthy cells, they use more iron than a typical cell. To capture and include more iron, cancer cells over express receptors specific to iron transporting proteins, TfR1, which internalize iron into the cell. Thus, cancer cells can be targeted by developing therapies which directly interact with these receptors, i.e.- using iron containing ferritin as a trojan horse. There are still outstanding issues that prevent a more complete understanding of the photochemistry of Ftn. Effective cancer therapies which specifically target cancer cells while leaving healthy cells unharmed are desired to treat a condition which kills ten million world-wide per year. Thus, there is a need in the art for improved compositions and methods for the application of ferritin (Ftn) photochemistry driven iron sequestration to the treatment of cancer. This invention satisfies this unmet need. SUMMARY OF THE INVENTION The present invention relates to, in part, a composition comprising a Ferritin-metal nanoparticle bioconjugate, wherein the Ferritin-metal nanoparticle Attorney Docket No.206017-0250-00US bioconjugate comprises at least one metal nanoparticle and at least one Ferritin or a variant or a fragment thereof conjugated to the at least one metal nanoparticle; and wherein the Ferritin-metal nanoparticle bioconjugate specifically targets at least one cell expressing a transferrin receptor 1 (TfR1). In one embodiment, the at least one Ferritin or a variant or a fragment thereof is selected from the group consisting of a human H-type Ferritin or a variant or a fragment thereof, horse spleen Ferritin or a variant or a fragment thereof, and any combination thereof. In one embodiment, wherein the at least one metal nanoparticle is selected from the group consisting of a metal nanorod, metal nanosphere, metal nanostar, and any combination thereof. In one embodiment, the at least one metal nanoparticle is selected from the group consisting of a gold nanoparticle, iron nanoparticle, copper nanoparticle, and any combination thereof. In one embodiment, the at least one metal nanoparticle further comprises an oxide coating. In one embodiment, the oxide coating is selected from the group consisting of a Fe2O3 coating, SiO2 coating, and any combination thereof. In one embodiment, the at least one Ferritin or a variant or a fragment thereof is conjugated to the at least one metal nanoparticle via a linker In one embodiment, the linker comprises N-succinimidyl S-acetylthioacetate or a derivative thereof. In one embodiment, the Ferritin-metal nanoparticle bioconjugate has an average hydrodynamic diameter of between 5 nm to 1,000 nm. In one embodiment, the Ferritin-metal nanoparticle bioconjugate has an average hydrodynamic diameter of between 10 nm to 300 nm. In one embodiment, the Ferritin-metal nanoparticle bioconjugate absorbs light having a wavelength of 200 nm to 1100 nm. In one embodiment, the Ferritin-metal nanoparticle bioconjugate releases at least one iron ion when irradiated with light having a wavelength of between 200 nm to 1100 nm. In one embodiment, the metal nanoparticle is a gold nanorod, and the bioconjugate has an average width of between 5 nm to 20 nm and an average length of between 30 nm to 70 nm. Attorney Docket No.206017-0250-00US In one embodiment, the metal nanoparticle is a gold nanostar, and the bioconjugate comprises between 3 to 7 spikes, and wherein the spikes have an average length of between 20 nm to 150 nm. In one embodiment, the metal nanoparticle is a gold nanosphere, and the bioconjugate has a surface area of between 50 nm2 to 900 nm2. In one embodiment, the Ferritin-metal nanoparticle bioconjugate further comprises a targeting domain. In one embodiment, the composition further comprises a therapeutic agent. In one embodiment, the at least one cell expressing a TfR1 is a cell overexpressing a TfR1. In one embodiment, the cell overexpressing a TfR1 is a cancer cell. The present invention further relates to, in part, a method of treating a disease or disorder associated with the level or activity of a T