Redox active cerium oxide nanoparticles and associated methods

• US 9,585,840 B1
• Filed: 07/13/2012
• Issued: 03/07/2017
• Est. Priority Date: 07/10/2009
• 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: Brenneisen, Peter, Seal, Sudipta, Karakoti, Ajay
• Primary Examiner(s): Shomer, Isaac
• Application Number:
  US13/548,795
• Time in Patent Office: 1,698 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 9/143 with inorganic compounds
• CPC Class Codes: A61K 9/5161 Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
• CPC Class Codes: C08K 2003/2213 of cerium
• CPC Class Codes: Y10S 977/773 Nanoparticle, i.e. structure having three dimensions of 100 nm or less
• CPC Class Codes: Y10S 977/911 Cancer cell destruction

Abstract

Nanoparticles disclosed in the invention comprise a dextran-coated crystalline structure of cerium oxide wherein tetravalent Ce⁴⁺ predominates over trivalent Ce³⁺ and wherein said nanoparticles have a diameter of approximately from 3 to 5 nm. The nanoparticles exhibit both superoxide dismutase activity and catalase activity in an environment having a substantially neutral or acidic pH. The nanoparticles may be used to make and may be contained in a medication. The subject nanoparticles are useful in a method of promoting a cytotoxic anti-invasive effect on squamous tumor cells and inhibit tumor invasiveness.

Claims

1. A method of promoting a cytotoxic anti-invasive effect on squamous tumor cells having an acidic internal cell environment, the method comprising contacting the cells with a nanoparticle composition comprising a cerium oxide core coated with dextran, wherein Ce⁴⁺ is in higher concentration than Ce³⁺ in the composition as measured by an absorption edge which lies beyond 350 nm, and wherein the nanoparticles have a diameter of approximately 3 to 5 nm, wherein the concentration of the nanoparticles in contact with the tumor cells is from 100 to 300 micromolar.

2. A method of inhibiting tumor invasiveness, the method comprising contacting tumor cells with a composition of dextran coated cerium oxide nanoparticles containing a predominance of Ce⁴⁺ over Ce³⁺ as measured by an absorption edge which lies beyond 350 nm, wherein the tumor cells are squamous cell skin cancer, wherein the concentration of the nanoparticles in contact with the tumor cells is from 100 to 300 micromolar.

3. The method of claim 2, wherein the nanoparticles have a diameter of approximately 3 to 5 nanometers.

4. A method of reducing tumor invasiveness of a squamous cell tumor, the method comprising contacting fibroblasts in the tumor'"'"'s stroma with a composition of dextran-coated cerium oxide nanoparticles having a predominance of Ce⁴⁺ over Ce³⁺ as measured by an absorption edge which lies beyond 350 nm, wherein the concentration of the nanoparticles in contact with the tumor cells is from 100 to 300 micromolar.

5. The method of claim 4, wherein the wherein the nanoparticles have a diameter of approximately 3 to 5 nanometers.

6. The method of claim 4, wherein the nanoparticles are toxic to squamous cell tumor cells and non-toxic to normal cells.

7. The method of claim 4, wherein the method inhibits the transition of fibroblasts to myofibroblasts.