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

Patent metadata

Field	Value
Publication number	US-2020163899-A1
Application number	US-201716083416-A
Country	US
Kind code	A1
Filing date	Mar 8, 2017
Priority date	Mar 8, 2016
Publication date	May 28, 2020
Grant date	—

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

1 . A combined method for treating a subject comprising:
administering a Prussian blue nanoparticle, a composition containing the nanoparticle, or a cell comprising the nanoparticle, to a subject in need thereof,
treating the subject with at least one other immunotherapy; and
photothermally treating the subject;
optionally wherein the immunotherapy comprises administering a T cell that is conjugated or otherwise associated with the Prussian blue nanoparticles, and
optionally, wherein the subject has cancer.

2 . The combined method of claim 1 , wherein the Prussian blue nanoparticles comprise Prussian blue.

3 . The combined method of claim 1 , wherein the Prussian blue nanoparticle consists essentially of Prussian blue.

4 . The combined method of claim 1 , wherein the Prussian blue nanoparticle comprises Prussian blue in an amount sufficient to permit it to participate in said photothermal treatment.

5 . The combined method of claim 1 , wherein the Prussian blue comprises, consists essentially of, or consists of a compound or composition having a chemical formula of:
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, Dyand 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, Dyand 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.

6 . The combined method of claim 1 , wherein the Prussian blue component comprises, consists essentially of, or consists of any one or more of the Prussian blue compounds disclosed by U.S. 2014/0271487 which is incorporated by reference.

7 . The combined method of claim 1 , wherein the nanoparticle has an average diameter ranging from about 1 nanometer to about 10 microns.

8 . The combined method of claim 1 , wherein the nanoparticle exhibits peak photonic absorbance at a wavelength ranging from about 600 nm to about 1,200 nm.

9 . The combined method of claim 1 , wherein the nanoparticle converts to heat absorbed incident light having a wavelength ranging from ranging from about 600 nm to about 1,200 nm by a photothermal conversion process or other mechanism.

10 . The combined method of claim 1 , wherein the nanoparticle converts to heat absorbed incident light having a wavelength ranging from ranging from about 600 nm to about 1,200 nm, wherein the amount of heat produced results in an increase in nanoparticle temperature ranging from 0.1 to 100° C.

11 . The combined method of claim 1 , wherein the nanoparticle converts to heat absorbed incident light having a wavelength ranging from ranging from about 600 nm to about 1,200 nm at a photothermal conversion efficiency ranging from about 0.1% to about 90%.

12 . The combined method of claim 1 , wherein the nanoparticle is coated, compounded or combined with at least one substance that reduces or prevents degradation of the Prussian blue component (e.g., degradation caused by contact with hydroxyl ions or other reactive components) in blood, plasma or lymph compared to an otherwise identical nanoparticle that is not coated, compounded or combined.

13 . The combined method of claim 1 , wherein the nanoparticle when introduced in vivo into blood, plasma, CSF, tissue fluid, lymph or other bodily fluids substantially prevents degradation of the Prussian blue component for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 30, 60, 120, 180 minutes or other time sufficient for the nanoparticle to come into contact with a cancer, neoplastic or tumor cell or other target cell; and optionally for a time sufficient for it to attach or endocytosed by said target cell, and optionally for a time sufficient for it to absorb radiation applied during a photothermal treatment.

14 . The combined method of claim 1 , wherein the nanoparticle comprises at least one, two or three protective layer(s) that reduces or prevents contact between the Prussian blue component of the nanoparticle and hydroxyl ions in blood, plasma or lymph.

15 . The combined method of claim 1 , wherein the nanoparticle comprises a nanoshell, liposome, micelle, or liposome-like synthetic particle.

16 . The combined method of claim 1 , wherein the nanoparticle comprises a coating.

17 . The combined method of claim 1 , wherein the nanoparticle comprises a coating selected from the group consisting of a polymer that comprises, consists essentially of, or consists of ADOGEN® 464, ALKANOL® 6112, BRIJ® 52, BRIJ® 93, BRIJ® S2, BRIJ® S, BRIJ® L4, BRIJ® O10, BRIJ® S 10, BRIJ® S20, Ethylenediamine tetrakis(ethoxylate-block-propoxylate) tetrol, IGEPAL® CA-210, IGEPAL® CA-520, IGEPAL® CA-720, IGEPAL® CO-630, IGEPAL® CO-890, IGEPAL® DM-970, MERPOL® DA, MERPOL® HCS, MERPOL® OJ, MERPOL® SE, MERPOL® SH, MERPOL® A, poly(ethylene glycol) sorbitan tetraoleate, poly(ethylene glycol) sorbitol hexaoleate, poly(ethylene glycol), polyethylene-block-poly(ethylene glycol), sorbitan monopalmitate, 2,4,7,9-tetramethyl-5-decyne-4,7-diol ethoxylate, 2,4,7,9-tetramethyl-5-decyne-4,7-diol, TRITON™ N-101, TRITON™ X-100, TRITON™ X-100 reduced, TRITON™ X-114, TRITON™ X-405, reduced, TWEEN® 20, TWEEN® 40, TWEEN® 60, TWEEN® 85, ZONYL® FS-300, ZONYL® FSA, ZONYL® FSN, ZONYL® FSO fluorosurfactant, acrylic acid (AA), 4,4′-azobis(4-cyanopentanoic acid); ACPA), 2,2′-azobisisobutyronitrile (AIBN), sodium bis(2-ethylhexyl) sulfosuccinate (AOT), sodium dihexyl sulfosuccinate (AMA-80), Amphi-Dex, acrylonitrile (AN), bis(2-pyridylmethyl)-octadecylamine (BPMODA), BRIJ® 30 (polyoxyethylene-4-lauryl ether), 1-butyl-3-methylimidazolium hexafluorophosphate ([C4mim]PF6), poly(oxyethylene) octyl phenyl ether (CA897),CMC-A9, carboxymethylated poly(ethylene glycol) (CMPEG), cetyltrimethylammonium bromide (CTAB), cetyltrimethylammonium chloride (CTMA-Cl), didodecyldimethylammonium bromide (DDAB), dodecanoic acid 2-(2-hydroxyethoxy)ethyl ester (DDA-HEEE), decyltrimethylammonioumbromide (DeTAB), dodecyl mercaptane (DDM), dextran ester (DexEst), SG1-based difunctional alkoxyamine (DIAMA-Na), dimethyl acetamide (DMAc), dodecyl methacrylate (DMA), (dimethylamino)ethyl methacrylate (DMAEMA), 3-(N,N-dimethylmyristylammonio) (DMMA-PS), dodecyl mercaptane, dodecyltrimethylammonioumbromide (DTAB), methacrylic acid copolymer (EUDRAGIT® L100-55), poly(ethylene-co-butylene)-b-poly(ethylene oxide) (KLE3729), lauryl methacrylate (LMA), monomethoxy-poly(ethylene glycol) (mPEG), monomethoxy-poly(ethylene oxide)-poly(lactic acid) (mPEO-PLA), methyl methacrylate (MMA), octyl trimethyl ammonium bromide (OTAB), polyaniline-poly(styrenesulfonic acid) (PANI-PSS), poly(γ-benzyl-1-glutamate)-b-poly(ethylene oxide) (PBG-PEO), poly(ε-caprolactum) (PCL), poly(oxyethylene)-poly(oxypropylene) copolymer (PE/F68), poly(ethylene oxide) (PEO), p

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 Mathieu F

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61K41/0052

  Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy · 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

• A61K33/26

  Iron; Compounds thereof · CPC title