Nanoparticles for photodynamic therapy, X-ray induced photodynamic therapy, radiotherapy, radiodynamic therapy, chemotherapy, immunotherapy, and any combination thereof

Patent metadata

Field	Value
Publication number	US-10806694-B2
Application number	US-201815884036-A
Country	US
Kind code	B2
Filing date	Jan 30, 2018
Priority date	Oct 14, 2014
Publication date	Oct 20, 2020
Grant date	Oct 20, 2020

Abstract

Metal-organic frameworks (MOFs) comprising photosensitizers are described. The MOFs can also include moieties capable of absorbing X-rays or other ionizing irradiation energy and/or scintillation. Optionally, the photosensitizer or a derivative thereof can form a bridging ligand of the MOF. Further optionally, the MOF can comprise inorganic nanoparticles in the cavities or channels of the MOF or can be used in combination with an inorganic nanoparticle. Also described are methods of using MOFs and/or inorganic nanoparticles in photodynamic therapy, X-ray induced photodynamic therapy, radiotherapy, radiodynamic therapy, or in radiotherapy-radiodynamic therapy, either with or without the co-administration of one or more immunotherapeutic agent and/or one or more chemotherapeutic agent.

First claim

What is claimed is:

1. A composition comprising a metal-organic framework (MOF) comprising:
a) a photosensitizer; and
b) a plurality of metal-containing secondary building units (SBUs) linked together via one or more bridging ligands, wherein the SBUs comprise hafnium (Hf) oxo clusters and wherein each of the one or more bridging ligands comprises an organic compound bound to two or three SBUs.

2. The composition of claim 1 , wherein the Hf oxo clusters are Hf 6 oxo clusters.

3. The composition of claim 1 , wherein the Hf oxo clusters are Hf 12 oxo clusters or a combination of Hf 12 and Hf 6 oxo clusters.

4. The composition of claim 1 , wherein each of the one or more bridging ligands comprises at least two groups wherein each of said two groups is individually selected from the group consisting of a carboxylate, a nitrogen-containing group, a phenol, an acetylacetonate, a phosphonate, and a phosphate.

5. The composition of claim 1 , wherein at least one of the one or more bridging ligands comprises the photosensitizer or a derivative of the photosensitizer.

6. The composition of claim 5 , wherein at least one of the one or more bridging ligands comprises a porphyrin, a chlorin, a chlorophyll, a phthalocyanine, a ruthenium-bipyridine complex, or an iridium-bipyridine complex.

7. The composition of claim 6 , wherein at least one of the one or more bridging ligands comprises a diphenyl-di(benzoate)porphyrin, a dibenzoato(bipyridine)ruthenium bis(bipyridine), or a dibenzoato-(bipyridine)ruthenium bis(phenylpyridine).

8. The composition of claim 1 , wherein at least one of the one or more bridging ligands comprises 5, 15-di(p-benzoato)porphyrin (DBP) or a derivative and/or metal complex thereof; 5, 15-di(p-benzoato)chlorin (DBC) or a derivative and/or metal complex thereof; 5, 15-di(p-benzoato)bacteriochlorin (DBBC) or a derivative and/or metal complex thereof; a platinum or palladium complex of di(5′-benzoatosalycylidene)-1,2-cyclohexylidenediamine; or motexafin lutetium.

9. The composition of claim 1 , further comprising a non-covalently bound chemotherapeutic agent and/or immunotherapeutic agent.

10. The composition of claim 9 , wherein the MOF further comprises a non-covalently bound immunotherapeutic agent, wherein said immunotherapeutic agent is an IDO inhibitor (IDOi).

11. The composition of claim 10 , wherein the IDOi is selected from the group consisting of ICBN24360, 1-methyl-D-tryptophan, and 1-methyl-L-tryptophan.

12. The composition of claim 1 , further comprising a polyethylene glycol (PEG) moiety and/or one or more lipid moiety bound covalently or electrostatically.

13. A pharmaceutical formulation comprising a composition of claim 1 and a pharmaceutically acceptable carrier.

14. A method for treating a cancer in a patient, the method comprising:
administering to a patient the composition of claim 1 ; and
exposing at least a portion of the patient to ionizing irradiation energy.

15. A method for treating a disease in a patient, wherein the disease is selected from a head and neck cancer, breast cancer, prostate cancer, a glioblastoma, a gynecological tumor, a brain tumor, colorectal cancer, and pancreatic cancer; the method comprising:
administering to a patient the composition of claim 1 ; and
exposing at least a portion of the patient to ionizing irradiation energy.

16. A method for treating a metastatic cancer in a patient, the method comprising:
administering to a patient the composition of claim 1 ; and
exposing at least a portion of the patient to ionizing irradiation energy.

17. A method for treating a disease in a patient, wherein the disease is selected from a head and neck cancer, breast cancer, prostate cancer, a glioblastoma, a gynecological tumor, a brain tumor, colorectal cancer, pancreatic cancer, and a metastatic cancer, the method comprising:
administering to a patient the composition of claim 1 ; and
exposing at least a portion of the patient to ionizing irradiation energy;

wherein the method further comprises administering to the patient an immunotherapy agent.

18. The method of claim 17 , wherein the immunotherapy agent is selected from the group consisting of a PD-1/PD-L1 antibody, an IDO inhibitor, CTLA-4 antibody, a OX40 antibody, a TIM3 antibody, a LAG3 antibody, an siRNA targeting PD-1/PD-L1, an siRNA targeting IDO and an siRNA targeting CCR7.

Assignees

• Univ Chicago

Inventors

• Lin Wenbin
• He Chunbai
• Lu Kuangda
• Ni Kaiyuan
• Lan Guangxu

Classifications

• A61K9/19

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• A61K31/409

  having four such rings, e.g. porphine derivatives, bilirubin, biliverdine (hemin, hematin A61K31/555) · CPC title

• A61K31/405

  Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin · CPC title