A phosphate-dependent shift in redox state of cerium oxide nanoparticles and its effects on catalytic properties

Abstract

Cerium oxide nanoparticles (CeNPs) have shown promise as catalytic antioxidants in cell culture and animal models as both superoxide dismutase and catalase mimetics. The reactivity of the cerium (Ce) atoms at the surface of its oxide particle is critical to such therapeutic properties, yet little is known about the potential for a protein or small molecule corona to form on these materials in vivo. Moreover Ce atoms in these active sites have the potential to interact with small molecule anions, peptides, or sugars when administered in culture or animal models. Several nanomaterials have been shown to alter or aggregate under these conditions, rendering them less useful for biomedical applications. In this work we have studied the change in catalytic properties of CeNPs when exposed to various biologically relevant conditions in vitro. We have found that CeNPs are resistant to broad changes in pH and also not altered by incubation in cell culture medium. However to our surprise phosphate anions significantly altered the characteristics of these nanomaterials and shifted the catalytic behavior due to the binding of phosphate anions to cerium. Given the abundance of phosphate in biological systems in an inorganic form, it is likely that the action of CeNPs as a catalyst may be strongly influenced by the local concentration of phosphate in the cells and/or tissues in which it has been introduced.

Attaching DNA to Nanoceria: Regulating Oxidase Activity and Fluorescence Quenching

“…Previous work has shown that the superoxide dismutase activity of nanoceria is inhibited by simple inorganic phosphate ions. 34 However, its oxidase activity is not significantly affected as shown in the current study. Only when DNA with poly-phosphate backbone is used, its oxidase activity was inhibited.…”

Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications

“…However, its antioxidative quality is only effective when the two enzyme-like activities of CeONP are coordinated, that is, the H 2 O 2 decomposition rate should be equal to or greater than its generation rate. According to recent reports, many factors such as particle size, Ce 3 þ /Ce 4 þ ratio, 32,43,50 buffer species 51 and pH conditions 51,52 could affect the enzyme-mimetic properties of CeONP.…”

“…For buffer species, exposure of CeONP to phosphate buffer would result in a decrease in SOD-mimetic activity and an increase in catalase-mimetic activity. 51 Given that phosphate is a basic substance in biological systems, its impact on the activity of CeONP should be taken into account when CeONP is used in cell culture or animal studies. However, the ability to reverse the 'poisoning' of the SOD-mimetic activity in vivo can be investigated in future studies.…”

“…The pH value could also influence the catalytic properties of CeONP. 51,52 The catalase-mimetic activity of CeONP under a physiological pH is significantly diminished when under an acidic pH, whereas the SOD activity of CeONP is only slightly affected over a variety of pH changes. This suggests that at a more acidic pH, CeONP cannot detoxify the hydrogen peroxide at the same rate as it can at neutral pH, whereas the rate for superoxide converting to peroxide is not affected.…”

Ceria Nanoparticles as Enzyme Mimetics

“…As mentioned above, CuZn-SOD or some appropriate electron donors can greatly improve the SOD mimetic activity of nanoceria. [21] A study conducted by Singh et al [89] reported that nanoceria lost SOD activity when it was exposed to high concentration of phosphate anions due to the binding of phosphate anions to cerium. As a result, cerium phosphate blocked the redox cycling between Ce 3＋ and Ce 4＋ , which was essential for antioxidant/ catalytic activity of nanoceria.…”