Polymer coated ceria nanoparticles for selective cytoprotection

• US 9,119,391 B1
• Filed: 07/08/2008
• Issued: 09/01/2015
• Est. Priority Date: 07/16/2007
• Status: Active Grant

• Current Assignee: University of Central Florida Research Foundation Inc. (State University System of Florida)
• Original Assignee: University of Central Florida Research Foundation Inc. (State University System of Florida)
• Inventors: Perez, Jesus Manuel, Asati, Atul, Nath, Sudip, Kaittanis, Charalambos
• Primary Examiner(s): Ware, Debbie K
• Assistant Examiner(s): Srivastava, Kailash C
• Application Number:
  US12/169,179
• Time in Patent Office: 2,611 Days
• US Class Current: 1/1
• CPC Class Codes: A01N 1/02 Preservation of living parts
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 9/5161 Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin

Abstract

Methods, systems and compositions are disclosed wherein normal, non-transformed, healthy biological cells are protected from oxidative stress, radiation therapy and chemotherapy while diseased, transformed cells, such as, cancer cells, are provided no protection by the biocompatible, polymer coated nanoceria composition of the present invention. The polymer-coated nanoceria preparation herein exhibits no toxicity to normal cells and exhibits pH-dependent antioxidant properties at neutral or physiological pH values, between approximately 6.5 to approximately 11.0 and is inactive as an antioxidant at acidic pH values between approximately 2.0 to approximately 6.4. Improved therapeutic agents and cytoprotecting devices are based on the newly discovered, pH dependent properties of polymer-coated nanoceria that provide selective cytoprotection.

Claims

1. A process for protecting normal, non-transformed biological cells using a pH-dependent therapeutic agent, comprising:

providing a plurality of biocompatible, polymer-coated cerium oxide nanoparticles having a pH-dependent antioxidant property, said polymer-coated cerium oxide nanoparticles being an active antioxidant in pH range from 7 to approximately 11 while having a substantially reduced antioxidant activity at an acidic pH from approximately 2 to 6, said polymer-coated cerium oxide nanoparticles not able to reversibly switch from Ce₃⁺ to Ce₄⁺ at said acidic pH; and

adding an effective amount of said polymer-coated cerium oxide nanoparticles to a cell environment containing normal biological cells and diseased biological cells so as to contact said normal biological cells and diseased biological cells, thereby selectively protecting said normal, non-transformed cells from hydroxyl-radical induced oxidative, nitroxyl-radical induced oxidative stress, radiation therapy, inflammation or chemotherapy, while providing no cytoprotection to said diseased cells.

2. The process of claim 1, wherein the normal biological cells have a pH value between approximately 6.5 to approximately 11.0 and the diseased biological cells have a pH value between approximately 2.0 and approximately 6.4.

3. The process of claim 1, wherein the plurality of biocompatible, polymer-coated cerium oxide nanoparticles are coated with a biodegradable polymer selected from at least one of a carbohydrate polymer, a synthetic polyol, a carboxylated polymer, and derivatives thereof.

4. The process of claim 1, wherein the polymer-coated cerium oxide nanoparticles are coated with a crosslinked-aminated biodegradable polymer selected from at least one of a carbohydrate polymer, a synthetic polyol, a carboxylated polymer and derivatives thereof.

5. The process of claim 1 wherein the normal biological cells include cardiomyocytes, dermal fibroblasts, lung tissue cells or breast tissue cells.

6. The process of claim 1, wherein the diseased biological cells include lung cancer cells, breast cancer cells, or dermal cancer cells.

7. The process of claim 3, wherein the biodegradable polymer is polyacrylic acid or polysaccharide.

8. The process of claim 7, wherein the polysaccharide is dextran.

9. The process of claim 3, wherein a colloidal suspension formed by the polymer-coated cerium oxide nanoparticles is stable in water or phosphate buffer solution.

10. The process of claim 4, wherein the biodegradable polymer is polyacrylic acid or polysaccharide.

11. The process of claim 10, wherein the polysaccharide is dextran.

12. The process of claim 4, wherein a colloidal suspension formed by the polymer-coated cerium oxide nanoparticles is stable in water or phosphate buffer solution.