Products and methods for organ protection with noble nanoparticles

Patent metadata

Field	Value
Publication number	US-12048714-B2
Application number	US-202016843114-A
Country	US
Kind code	B2
Filing date	Apr 8, 2020
Priority date	Apr 8, 2020
Publication date	Jul 30, 2024
Grant date	Jul 30, 2024

Abstract

Products and methods for redirecting the pathological biochemical process of accumulation of reduced pyridine nucleotides under deleterious hypoxia conditions toward the reduction of the precursor salt and the biosynthesis of biologically compatible, antioxidant noble metal nanoparticles and the simultaneous restoring of the tissue redox state are provided. The products and methods have application in the treatment of hypoxia and hypoxia-related diseases and disorders. Such products and methods are also useful in organ transplantation and recovery, in screening of anti-hypoxia agents, and in detecting elevated levels of the reducing equivalents of the redox state, for example, NADH, NADPH, GSH, and TrxSH2, in cells, tissues, or organs.

First claim

We claim:

1. A method of preserving an isolated cell, tissue, or organ ex vivo for transplantation, the method comprising:
administering ex vivo to the isolated cell, tissue, or organ an effective amount of a noble metal precursor to form a noble metal nanoparticle in situ and increase the ratio of oxidized to reduced forms of nicotinamide adenine dinucleotide (NAD+/NADH), nicotinamide adenine dinucleotide phosphate (NADP+/NADPH), glutathione (GSSG/GSH), or thioredoxin (TrxSS/TrxSH 2 ) in the isolated cell, tissue, or organ;
wherein the noble metal precursor is selected from the group consisting of a noble metal halide, a noble metal hydroxide, a noble metal chloride, a complex of any one of the foregoing with one or more organic ligands, and combinations thereof; and
wherein the noble metal of the precursor is selected from the group consisting of gold (Au), silver (Ag), platinum (Pt), palladium (Pd), ruthenium (Ru), rhodium (Rh), osmium (Os), and iridium (Ir).

2. The method of claim 1 , wherein increasing the ratio of NAD+/NADH, NADP+/NADPH, GSSG/GSH, or TrxSS/TrxSH 2 reduces production of reactive oxygen species, reduces reactive nitrogen species, and/or reduces apoptosis.

3. The method of claim 1 , wherein the noble metal nanoparticle reduces the accumulation of reduced pyridine nucleotides in the cell, tissue, or organ.

4. The method of claim 1 , wherein the cell, tissue, or organ is suffering from or is at risk of suffering from a deficiency of oxidized forms of nicotinamide adenine dinucleotide (NAD+), nicotinamide adenine dinucleotide phosphate (NADP+), glutathione (GSSG), or thioredoxin (TrxSS).

5. The method of claim 1 , wherein the noble metal precursor is a gold chloride.

6. The method of claim 5 , wherein the gold chloride is gold monochloride (AuCl), gold dichloride (AuCl 2 ), gold trichloride (AuCl 3 ), tetragold octachloride (Au 4 Cl 8 ), or chloroauric acid (HAuCl 4 ).

7. The method of claim 1 , wherein the cell is a brain cell, a cardiac cell, a kidney cell, a lung cell, a liver cell, a stomach cell, an intestinal cell, a pancreatic cell, a blood cell, a retinal cell, a skin cell, or other cell of the eye.

8. The method of claim 1 , wherein the cell is a non-cancerous tumor cell.

9. The method of claim 1 , wherein the tissue is isolated from the brain, the heart, the kidney, the lung, the liver, the stomach, the intestine, the pancreas, the blood, the retina, or the skin.

10. The method of claim 1 , wherein the organ is the heart, the kidney, the lung, the liver, the stomach, the intestine, the pancreas, the blood, the retina, or the skin.

11. The method of claim 1 , wherein the effective amount is from about 0.1 pmol/g to about 1 mol/g.

12. The method of claim 1 , wherein the effective amount is administered at a concentration from about 1 nM to about 1 M.

Assignees

• Uchicago Argonne Llc

Inventors

• Rozhkova Elena A
• Shevchenko Elena

Classifications

• G01N33/502

  for testing non-proliferative effects · CPC title

• A61K9/5115

  Inorganic compounds · CPC title

• A61P39/06 Primary

  Free radical scavengers or antioxidants · CPC title

• G01N33/5008

  for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics · CPC title

• A61K9/0048

  Eye, e.g. artificial tears · CPC title