Oxidase activity of polymeric coated cerium oxide nanoparticles

• US 8,883,519 B1
• Filed: 02/12/2010
• Issued: 11/11/2014
• Est. Priority Date: 03/17/2009
• 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, J. Manuel, Asati, Atul, Santra, Santimukul, Kaittanis, Charalambos, Nath, Sudip
• Primary Examiner(s): Nguyen, Bao Thuy L
• Assistant Examiner(s): DO, PENSEE T
• Application Number:
  US12/704,678
• Time in Patent Office: 1,733 Days
• Field of Search: 436/525, 436/518
• US Class Current: 436/525
• CPC Class Codes: B01J 2231/005 General concepts, e.g. reviews, relating to methods of using catalyst systems, the concept being defined by a common method or theory, e.g. microwave heating or multiple stereoselectivity
• CPC Class Codes: B01J 31/26 containing in addition, inorganic metal compounds not provided for in groups B01J31/02 - B01J31/24
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: G01N 33/5432 Liposomes or microcapsules
• CPC Class Codes: G01N 33/54346 Nanoparticles
• CPC Class Codes: G01N 33/57423 of lung
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: G01N 33/587 Nanoparticles
• CPC Class Codes: G01N 33/9413 Dopamine

Abstract

Methods, systems, compositions include biocompatible polymer coated nanoceria that function as aqueous redox catalyst with enhanced activity at an acidic to moderately alkaline pH value between 1 and 8. The compositions are used as oxidizing agents for decomposition, decontamination or inactivation of organic contaminants, such as, pesticides and chemical warfare agents. Another use includes nanoceria as targetable nanocatalyst prepared by conjugating various targeting ligands to the nanoparticle coating to form a colorimetric or fluorescent probe in immunoassays and other molecule binding assays that involve the use of a molecule in solution that changes the color of the solution or emits a fluorescent signal, where localization of nanoceria to organs or tissue is assessed by treatment with an oxidation sensitive dye or other detection devices. Versatility and uses of the nanoceria compositions are controlled by pH value, choice of dye substrate and thickness of the polymer coating on the ceria nanoparticles.

Claims

1. Polymer coated cerium oxide nanoparticles, each comprising a cerium oxide core with an average hydrodynamic diameter of approximately 7 nm, and a polymer coating with a thickness to an extent such that said polymer coated cerium oxide nanoparticles have an average hydrodynamic diameter in a range from approximately 12 nm to approximately 100 nm, wherein oxidant property of the polymer coated cerium oxide nanoparticles varies with the thickness of the polymer coating of the polymer coated cerium oxide nanoparticles, and is pH dependent.

2. The polymer coated cerium oxide nanoparticles of claim 1, wherein the oxidant property of the polymer coated cerium oxide nanoparticles decreases with an increase in the thickness of the polymer coating of the polymer coated cerium oxide nanoparticles.

3. The polymer coated cerium oxide nanoparticles of claim 1, wherein said polymer coated cerium oxide nanoparticles are formed by mixing a biocompatible polymer with an aqueous reaction mixture of a cerium salt and ammonium hydroxide after an initial formation of cerium oxide nanoparticles in the reaction mixture, thereby obtaining said average hydrodynamic diameters of the cerium oxide core and the polymer coated nanoparticles.

4. The polymer coated cerium oxide nanoparticles of claim 1, wherein the biocompatible polymer is at least one selected from the group consisting of carbohydrate polymer, synthetic polyol, carboxylated polymer, and derivatives thereof.

5. The polymer coated cerium oxide nanoparticles of claim 4, wherein the carboxylated polymer is polyacrylic acid.

6. The polymer coated cerium oxide nanoparticles of claim 5, wherein the polysaccharide is dextran.

7. The polymer coated cerium oxide nanoparticles of claim 4, wherein the carbohydrate polymer is a polysaccharide.

8. The polymer coated cerium oxide nanoparticles of claim 4, wherein the carbohydrate polymer is reduced dextran, carboxyl methyl reduced dextran, arabinogalactan, or chitosan.

9. The polymer coated cerium oxide nanoparticles of claim 1, wherein the polymer coated cerium oxide nanoparticles exhibit oxidant property in an acidic condition with pH between approximately 1 and approximately 4.

10. The polymer coated cerium oxide nanoparticles of claim 1, wherein the polymer coated cerium oxide nanoparticles are polyacrylic acid-coated cerium oxide nanoparticles having the average hydrodynamic diameter approximately 12 nm.

11. The polymer coated cerium oxide nanoparticles of claim 1, wherein the polymer coated cerium oxide nanoparticles are dextran-coated cerium oxide nanoparticles having the average hydrodynamic diameter approximately 100 nm.

12. The polymer coated cerium oxide nanoparticles of claim 1, wherein the polymer coated cerium oxide nanoparticles further comprise a ligand conjugated to the polymer coating.

13. The polymer coated cerium oxide nanoparticles of claim 12, wherein the ligand is folic acid and the polymer coated cerium oxide nanoparticles are folate-conjugated.

14. The polymer coated cerium oxide nanoparticles of claim 12, wherein the polymer coated cerium oxide nanoparticles having a conjugated ligand bind specifically to a target of an immunoassay and also oxidize a dye for detection in the immunoassay.

15. The polymer coated cerium oxide nanoparticles of claim 1, wherein the polymer coated cerium oxide nanoparticles further comprise an antibody conjugated to the polymer coating.

16. The polymer coated cerium oxide nanoparticles of claim 15, wherein the polymer coated cerium oxide nanoparticles having a conjugated antibody enable detection of a target in a horseradish peroxidase based immunoassay in the absence of the horseradish peroxidase and hydrogen peroxide.

17. The polymer coated cerium oxide nanoparticles of claim 1, wherein the polymer coated cerium oxide nanoparticles are a redox catalyst with an enhanced activity at an acidic pH between approximately 1 and approximately 4.

18. The polymer coated cerium oxide nanoparticles of claim 1, wherein the polymer coated cerium oxide nanoparticles are an oxidizing agent in decomposition, decontamination and inactivation of organic contaminants, pesticides, nerve agents or chemical warfare agents at an acidic pH between approximately 1 and approximately 4.

19. The polymer coated cerium oxide nanoparticles of claim 1, wherein at an acidic pH between approximately 1 and approximately 4 the biocompatible polymer coated cerium oxide nanoparticles are an oxidant to chromogenic dyes, fluorescent dyes, and photoluminescent dyes used for peroxidase or oxidase detection, and enable to oxidize the dyes to cause a color change.

20. The polymer coated cerium oxide nanoparticles of claim 19, wherein said dyes comprise 3,3′

,5,5′

-tetramethyl benzidine (TMB) or 2,2-azinobis-(3-ethylbenzothizoline-6-sulfonic acid) (AzBTS).

21. A reagent for use in biochemical analysis and detection comprising a plurality of polymer coated cerium oxide nanoparticles, each thereof comprising a cerium oxide core with an average hydrodynamic diameter of approximately 7 nm, and a polymer coating with a thickness to an extent such that said polymer coated cerium oxide nanoparticles have an average hydrodynamic diameter in a range from approximately 12 nm to approximately 100 nm, wherein oxidant property of the polymer coated cerium oxide nanoparticles varies with the thickness of the polymer coating of the polymer coated cerium oxide nanoparticles, and is pH dependent.

22. The diagnostic device reagent of claim 21, wherein the oxidant property of the polymer coated cerium oxide nanoparticles decreases with an increase in the thickness of the polymer coating of the polymer coated cerium oxide nanoparticles.

23. The reagent of claim 21, wherein said polymer coated cerium oxide nanoparticles are formed by mixing a biocompatible polymer with an aqueous reaction mixture of a cerium salt and ammonium hydroxide after an initial formation of cerium oxide nanoparticles in the reaction mixture, thereby obtaining said average hydrodynamic diameters of the cerium oxide core and the polymer coated nanoparticles.

24. The reagent of claim 21, wherein the biocompatible polymer is at least one selected from the group consisting of carbohydrate polymer, synthetic polyol, carboxylated polymer, and derivatives thereof.

25. The reagent of claim 24, wherein the carboxylated polymer is polyacrylic acid.

26. The reagent of claim 24, wherein the carbohydrate polymer is a polysaccharide.

27. The reagent of claim 26, wherein the polysaccharide is dextran.

28. The reagent of claim 24, wherein the carbohydrate polymer is reduced dextran, carboxyl methyl reduced dextran, arabinogalactan, or chitosan.

29. The reagent of claim 21, wherein the polymer coated cerium oxide nanoparticles are polyacrylic acid-coated cerium oxide nanoparticles having the average hydrodynamic diameter approximately 12 nm.

30. The reagent of claim 21, wherein the polymer coated cerium oxide nanoparticles are dextran-coated cerium oxide nanoparticles having the average hydrodynamic diameter approximately 100 nm.

31. The reagent of claim 21, wherein the polymer coated cerium oxide nanoparticles further comprise a ligand conjugated to the polymer coating.

32. The reagent of claim 31, wherein the polymer coated cerium oxide nanoparticles having a conjugated ligand bind specifically to a target of an immunoassay and also oxidize a dye for detection in the immunoassay.

33. The reagent of claim 21, wherein the ligand is folic acid and the polymer coated cerium oxide nanoparticles are folate-conjugated.

34. The reagent of claim 21, wherein folate-conjugated polymer coated cerium oxide nanoparticles are specific to folate receptors of cells.

35. The reagent of claim 21, wherein the polymer coated cerium oxide nanoparticles further comprise an antibody conjugated to the polymer coating.

36. The reagent of claim 35, wherein the polymer coated cerium oxide nanoparticles having a conjugated antibody enable detection of a target in a horseradish peroxidase based immunoassay in the absence of the horseradish peroxidase and hydrogen peroxide.

37. The reagent of claim 21, wherein at an acidic pH between approximately 1 and approximately 4 the biocompatible polymer coated cerium oxide nanoparticles are an oxidant to chromogenic dyes, fluorescent dyes, and photoluminescent dyes used for peroxidase or oxidase detection, and enable to oxidize the dyes to cause a color change.

38. The reagent of claim 37, wherein said dyes comprise 3,3′

,5,5′

-tetramethyl benzidine (TMB) or 2,2-azinobis-(3-ethylbenzothizoline-6-sulfonic acid) (AzBTS).