Anti-Inflammatory, Radioprotective, and Longevity Enhancing Capabilities of Cerium Oxide Nanoparticles

Abstract

The present invention provides cerium oxide nanoparticles for use both in therapeutic compositions in vivo and in research in vitro. The cerium oxide nanoparticles are of a known range of sizes having biological properties that are reproducible and beneficial. Pharmaceutical and other compositions are provided, as are methods of treatment.

1 - 93 . (canceled) 
   
   
       94 . Cerium oxide nanoparticles having a size range of from 11 nm to 500 nm. 
   
   
       95 . The cerium oxide nanoparticles of  claim 94 , wherein the nanoparticles have been sonicated to avoid agglomeration. 
   
   
       96 . A composition comprising the nanoparticles of  claim 94 , further comprising one or more biologically tolerable substances. 
   
   
       97 . The composition of  claim 96 , wherein the biologically tolerable substance is one or more of water, a salt, phosphate buffered saline, and a lipid. 
   
   
       98 . Cerium oxide nanoparticles having a size range of less than 1 nm to about 500 nm, in an amount sufficient to provide a single dose of particles to an animal to reduce or eliminate clinical symptoms resulting from damage due to free radicals in cells of the animal, or to prevent such clinical symptoms. 
   
   
       99 . Cerium oxide nanoparticles having a size range of less than 1 nm to about 500 nm, in an amount sufficient to provide a single dose of particles to an animal to reduce, eliminate, or prevent clinical symptoms resulting from inflammatory responses in cells of the immune system or to decrease the inflammatory capacity of cells of the immune system. 
   
   
       100 . A composition comprising a pharmaceutically suitable substance and the cerium oxide nanoparticles of  claim 98 . 
   
   
       101 . A composition comprising the cerium oxide nanoparticles of  claim 98 , further comprising one or more substances having a beneficial effect on the diet or nutrition of the animal. 
   
   
       102 . The composition of  claim 101 , which is a nutritional supplement or dietary supplement for the animal. 
   
   
       103 . A kit comprising the cerium oxide nanoparticles of  claim 98 . 
   
   
       104 . The kit of  claim 103 , wherein the cerium oxide nanoparticles are of a size range between 11 nm and 500 nm. 
   
   
       105 . A medical prosthesis made from joint replacements or joint additives coated with or containing cerium oxide nanoparticles of a size of at least about 1 nm to 500 nm in an amount sufficient to reduce inflammation in the subject. 
   
   
       106 . A method of increasing cell longevity, said method comprising:
 contacting a cell to cerium oxide nanoparticles of  claim 94  in an amount sufficient to result in increased cell longevity.   
   
   
       107 . The method of  claim 106 , wherein the amount of nanoparticles is sufficient to reduce free radical damage within the cell. 
   
   
       108 . The method of  claim 106 , wherein the cerium oxide nanoparticles are produced from a process other than a sol-gel method. 
   
   
       109 . The method of  claim 106 , wherein the amount of nanoparticles is sufficient to prevent aging of cells of a subject. 
   
   
       110 . The method of  claim 106 , wherein the size of the cerium oxide nanoparticles is from 11 nm to about 50 nm. 
   
   
       111 . The method of  claim 106 , wherein the size of the cerium oxide nanoparticles is from 40 nm to about 500 nm. 
   
   
       112 . The method of  claim 106 , wherein the cerium oxide particles have a size of about 20 nm. 
   
   
       113 . The method of  claim 106 , wherein greater than 95% of the cerium oxide particles have a size of between about 5 nm and about 40 nm. 
   
   
       114 . The method of  claim 106 , which is a method of radioprotection of cells exposed to radiation during a cancer treatment regimen or a method of prevention or treatment of brain disease, a spinal cord disease, neurological trauma, a neurodegenerative disorder, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, toxin-mediated damage, stroke, arthritis, joint disease, atherosclerosis, cardiovascular disease, diabetes, diseases of the retina, an allergy, asthma, chronic obstructive pulmonary disease, respiratory dysfunction, an autoimmune disease, inflammation, or a wound. 
   
   
       115 . The method of  claim 106 , which is an in vitro method. 
   
   
       116 . The method of  claim 106 , which is an ex vivo method in which at least one cell is removed from a multi-cellular organism, treated with the cerium oxide nanoparticles, and then returned to the organism. 
   
   
       117 . The method of  claim 116 , in which the blood from an organism is exposed to the cerium oxide nanoparticles, and then returned to the organism. 
   
   
       118 . An in vivo method of treating at least one cell with cerium oxide nanoparticles comprising:
 contacting the cell with cerium oxide nanoparticles of  claim 98 .   
   
   
       119 . The method of  claim 118 , wherein the size of the cerium oxide nanoparticles is from 11 nm to about 50 nm. 
   
   
       120 . The method of  claim 118 , wherein the cerium oxide particles have a size of about 20 nm. 
   
   
       121 . The method of  claim 118 , wherein greater than 95% of the cerium oxide particles have a size of between about 5 nm and about 40 nm. 
   
   
       122 . The method of  claim 118 , which is a method of radioprotection of cells exposed to radiation during a cancer treatment regimen or a method of prevention or treatment of brain disease, a spinal cord disease, neurological trauma, a neurodegenerative disorder, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, toxin-mediated damage, stroke, arthritis, joint disease, atherosclerosis, cardiovascular disease, diabetes, diseases of the retina, an allergy, asthma, chronic obstructive pulmonary disease, respiratory dysfunction, an autoimmune disease, inflammation, or a wound. 
   
   
       123 . A method of determining the effects of one or more environmental stimuli on free radical production in a cell, said method comprising:
 contacting at least one cell with cerium oxide nanoparticles of a size of at least 11 nm to provide treated cells;   optionally providing identical cells, but which are not contacted with cerium oxide nanoparticles to provide control cells;   observing the treated and, where provided, control cells for detectable changes in free radical levels; and   optionally, comparing the free radical levels in the treated and control cells.   
   
   
       124 . The method of  claim 123 , wherein the environmental stimuli is one or more chemicals.