Virus-like particle conjugates for diagnosis and treatment of tumors
View Patent ↗The present disclosure is directed to methods and compositions for the diagnosis and/or treatment of tumors, such as ocular tumors, using virus-like particles conjugated to photosensitive molecules.
1. A tumor-targeting papilloma virus-like particle comprising about 50 to about 500 near infrared phthalocyanine dye molecules conjugated to papilloma virus capsid proteins, wherein the near infrared phthalocyanine dye molecules become toxic or produce a toxic molecule upon light activation.
2. The tumor-targeting papilloma virus-like particle of claim 1 , wherein the papilloma virus capsid proteins are non-human papilloma virus capsid proteins.
3. The tumor-targeting papilloma virus-like particle of claim 1 , wherein the papilloma virus-like particle comprises human papilloma virus (HPV) L1 capsid proteins.
4. The tumor-targeting papilloma virus-like particle of claim 3 , wherein the HPV L1 capsid proteins comprise modified HPV L1 capsid proteins, relative to wild-type HPV L1 capsid proteins, and wherein the modified HPV L1 capsid proteins do not cross-react with neutralizing antibodies to HPV 16 or HPV 18.
5. The tumor-targeting papilloma virus-like particle of claim 4 , wherein the modified HPV L1 capsid proteins comprise a combination of modified HPV L1 capsid proteins and wild-type HPV L2 capsid proteins.
6. The tumor-targeting papilloma virus-like particle of claim 4 , wherein the tumor-targeting papilloma virus-like particle has reduced immunogenicity and/or antigenicity relative to a virus-like particle comprising wild-type HPV L1 capsid proteins.
7. The tumor-targeting papilloma virus-like particle of claim 1 , wherein the near infrared phthalocyanine dye molecules are covalently conjugated to the papilloma virus capsid proteins.
8. The tumor-targeting papilloma virus-like particle of claim 1 , wherein the near infrared phthalocyanine dye molecules are conjugated to lysine residues of the papilloma virus capsid proteins.
9. The tumor-targeting papilloma virus-like particle of claim 7 , wherein the near infrared phthalocyanine dye molecules are conjugated to the capsid proteins through covalent amide bonds.
10. The tumor-targeting papilloma virus-like particle of claim 1 , wherein the near infrared phthalocyanine dye molecules do not compromise binding of the tumor-targeting papilloma virus-like particle to the surface of tumor cells, or wherein the near infrared phthalocyanine dye molecules do not compromise binding of the tumor-targeting papilloma virus-like particle to heparan sulphate proteoglycans on the surface of tumor cells.
11. The tumor-targeting papilloma virus-like particle of claim 1 , wherein the near infrared phthalocyanine dye molecules comprise photosensitizer molecules that are promoted to an excited state upon absorption of light and undergo intersystem crossing with oxygen to produce singlet oxygen.
12. A method, comprising:
administering, to a subject having a tumor, the tumor-targeting papilloma virus-like particle of claim 1 .
13. A method, comprising:
administering, to a subject having an ocular tumor, a tumor-targeting papilloma virus-like particle comprising about 50 to about 1000 photosensitive molecules that become toxic or produce a toxic molecule upon light activation.
14. The method of claim 13 , wherein the ocular tumor is located in the vitreous, choroidal space, iris, ciliary body, sclera, fovea, retina, optic disk, or optic nerve.
15. The method of claim 13 , wherein the tumor-targeting papilloma virus-like particle is administered topically, intraocularly, intravitreally, or suprachoroidally.
16. The tumor-targeting papilloma virus-like particle of claim 1 , wherein the near infrared phthalocyanine dye molecules comprise IR700 dye molecules conjugated to capsid proteins.
17. The tumor-targeting papilloma virus-like particle of claim 1 , comprising about 200 near infrared phthalocyanine dye molecules.
18. The tumor-targeting papilloma virus-like particle of claim 1 , comprising about 300 near infrared phthalocyanine dye molecules.
19. The tumor-targeting papilloma virus-like particle of claim 1 , comprising about 400 near infrared phthalocyanine dye molecules.
20. The method of claim 12 , wherein the tumor is an ocular tumor located in the vitreous, choroidal space, iris, ciliary body, sclera, fovea, retina, optic disk, or optic nerve.
21. The method of claim 12 , wherein the tumor is located in a lung, pleura, liver, pancreas, stomach, esophagus, colon, breast, ovary, prostate, brain, meninges, testis, kidneys, or bladder.
22. The method of claim 12 , wherein the tumor-targeting papilloma virus-like particle is administered topically, intraocularly, intravitreally, or suprachoroidally.