19.4Biological Effect, Functional Mechanism, and Applications

High-speed ßuorescence microspectrophotometry showed that nanoceria shift from lower excitation energies (354Ð356 nm) to higher excitation energies (451 nm) followed by a slow return to the original spectra during radical challenge suggesting oxidation of Ce3+ sites to Ce4+ by free radicals and the return to lower excitation energies indicating the Ce3+ site as regenerative for the redox cycle [10, 19]. Although not yet established, we speculate that the ÒdefectsÓ in the lattice structure of nanoceria act as reactive sites for free radical scavenging. Nanoceria have been shown to directly act as biological antioxidants [33, 34]. The combination of properties of nanoceria, such as biocompatibility, small size, and cell and nuclear membrane permeability [15, 21, 24, 35], have resulted in their wide utilization in a variety of biological Þelds [11]. To test the ability of the CNPs to react with superoxide, two preparations were used. Preparation A consisted of polycrystalline particles of 3Ð5 nm with Ce3+ concentration of 40%, while preparation B consisted of hard, agglomerated 5Ð8 nm particles with Ce3+ concentration of 22% [36]. The ferricytochrome C assay demonstrated that preparation A exhibited superoxide dismutase (SOD) activity in a redox-state dependent manner and that the ability to scavenge superoxide is directly related to Ce3+ concentrations at the surface of the particle. Preparation B also displayed SOD activity, but was far less efÞcient [36]. The SOD mimetic activity of CNPs was conÞrmed by electron paramagnetic resonance (EPR) analysis [37]. The ÒAmplex RedÓ assay showed that preparation B exhibited signiÞcant catalase mimetic activity and that the breakdown of hydrogen peroxide was dependent on the Ce4+ state [38]. Moreover, modiÞcation of CNPs (PEGylation) did not reduce their regenerative capacity and SOD activities [20].

The molecular mechanism underlying the catalysis is currently unknown. The possible chemical reaction is as follows [39]:

Ce3+ → Ce4+ + eÐ

←

Ce3+ + OH· → Ce4+ + OHÐ

Ce4+ + O2·Ð → Ce3+ + O2

19.4.1Bacteria

CeO2 nanoparticles can be absorbed by the outer membrane of Escherichia coli and induce toxicity through reduction on the surface of bacteria [40] which was shown to be dependent on the Ce4+ absorbance of UV light and oxygen storage [41].