Functionalized Prussian blue nanoparticles, combination Prussian blue nanoparticle-based nano-immunotherapy and applications thereof

Patent metadata

Field	Value
Publication number	US-11931465-B2
Application number	US-201716083416-A
Country	US
Kind code	B2
Filing date	Mar 8, 2017
Priority date	Mar 8, 2016
Publication date	Mar 19, 2024
Grant date	Mar 19, 2024

Abstract

Combination treatment with Prussian blue nanoparticles and at least one immunotherapeutic treatment. Stable, functionalized Prussian blue nanoparticles, including those with enhanced stability under alkaline conditions, and methods of cancer, neoplasm, and tumor treatment using them, including photothermal treatment and combination immunotherapeutic treatments.

First claim

The invention claimed is:

1. A combined immunotherapeutic and photothermal method for treating a subject having a neoplasm, tumor, or cancer comprising:
treating the subject with an immunotherapy that comprises administering a checkpoint inhibitor which is an anti-CTLA-4 checkpoint inhibitor and/or an anti-PD-1/PD-L1 checkpoint inhibitor and wherein the checkpoint inhibitor is selected from the group consisting of ipilimumab, nivolumab, pembrolizumab and atezolizumab,
administering intratumorally Prussian blue nanoparticles comprising Prussian blue nanoparticles coated with first and second polymer coatings having opposite charges to each other; and
photothermally treating the subject; wherein the neoplasm, tumor or cancer is neuroblastoma; and wherein the first and second polymer coatings comprise polyallylamine hydrochloride and poly(acrylic acid).

2. The method of claim 1 , wherein the Prussian blue nanoparticles comprise a compound having the chemical formula:
A x B y M z [M′(CN 6 ] a ·n (H 2 O)

wherein:
A represents at least one of VO″, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, In, Ga, Sr, lr, Nb, Li, Na, K, Rb, Cs, Fr, TI, Mo, Ru, Rh, Pd, Ag, Cd, In, Lu, Ba, Hf, Ta, W, Os, Pt, Hg, La, Eu, Gd, Tb, Dy and Ho, in any oxidation state and any combination thereof;
B represents at least one of VO″, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, In, Ga, Sr, lr, Nb, Li, Na, K, Rb, Cs, Fr, TI, Mo, Ru, Rh, Pd, Ag, Cd, In, Lu, Ba, Hf, Ta, W, Os, Pt, Hg, La, Eu, Gd, Tb, Dy and Ho, in any oxidation state and any combination thereof;
M represents at least one of VO″, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, In, Ga, Sr, lr, Nb, Li, Na, K, Rh, Cs, Fr, TI, Mo, Ru, Rh, Pd, Ag, Cd, In, Lu, Ba, Hf, Ta, W, Os, Pt, Hg, La, Eu, Gd, Tb, Dy and Ho, in any oxidation state and any combination thereof;
M′ represents at least one of VO″, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, In, Ga, Sr, lr, Nb, Li, Na, K, Rb, Cs, Fr, TI, Mo, Ru, Rh, Pd, Ag, Cd, In, Lu, Ba, Hf, Ta, W, Os, Pt, Hg, La, Eu, Gd, Tb, Dy and Ho, in any oxidation state and any combination thereof;
x is from 0.1 to about 1;
Y is from 0 to about 1;
z is from 0.1 to about 4;
a is from 0.1 to about 4; and
n is from 0.1 to about 24.

3. The method of claim 2 , wherein in the formula
A x B y M z [M′(CN 6 ] a ·n (H 2 O), A=B=K.

4. The method of claim 2 , wherein the Prussian blue nanoparticles comprise KFe(Fe(CN) 6 ).

5. The method of claim 2 , wherein in the formula
A x B y M z [M′(CN 6 ] a ·n (H 2 O), A=K and B=Gd.

6. The method of claim 2 , wherein in the formula A x B y M z [M′(CN 6 ] a ·n (H 2 O), A=K and B=Mn.

7. The method of claim 1 , wherein the immunotherapy further comprises administering T cells.

8. The method of claim 1 , wherein the immunotherapy further comprises administering T cells that recognize at least one cancer antigen.

9. The method of claim 1 , where in the first and second polymer coatings comprise polyallylamine hydrochloride (PAH) and poly(acrylic acid)(PAA) further coated with polyethylene glycol (PEG) in the following order from core to surface: Prussian blue nanoparticles, PAH, PAA and PEG.

10. The method of claim 1 , wherein the immunotherapy comprises administering the anti-CTLA-4 checkpoint inhibitor ipilimumab.

11. The method of claim 1 , wherein the immunotherapy comprises administering an anti-PD-1/PD-L1 checkpoint inhibitor comprising nivolumab, pembrolizumab or atezolizumab.

12. The method of claim 1 , wherein the T cells or the checkpoint inhibitors are conjugated to the Prussian blue nanoparticles.

13. The method of claim 1 , wherein the Prussian blue nanoparticles have an average size ranging from 1 nm to 10 microns.

14. The method of claim 1 , wherein the nanoparticles further comprise an antibody, aptamer, or other ligand that binds to a cancer cell antigen.

15. The method of claim 1 , wherein the photothermal treatment comprises radiating the Prussian blue nanoparticles with light having a wavelength of 600 nm to 1,200 nm.

Assignees

• Childrens Nat Medical Ct

Inventors

• Fernandes Rohan
• Sze Raymond W
• Cruz Conrad Russell Y
• Sandler Anthony D
• Bollard Catherine M
• Sweeney Elizabeth E
• Cano-Mejia Juliana
• Burga Rachel
• Dumont Matthieu F

Classifications

• A61K40/42

  Cancer antigens · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• A61K9/5146 Primary

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides · CPC title

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61K9/5068

  Cell membranes or bacterial membranes enclosing drugs (liposomes with additional exogenous lipids A61K9/127) · CPC title