Nanoceria, typically used for "clean-air" catalytic converter technologies because of its ability to capture, store, and release oxygen, is the same material that has the potential to be used in nanomedicine. Specifically, nanoceria can be used to control oxygen content in cellular environments; as a "nanozyme", nanoceria mimics enzymes by acting as an antioxidant agent. The computational design procedures for predicting active materials for catalytic converters can therefore be used to design active ceria nanozymes. Crucially, the ceria nanomedicine is not a molecule; rather, it is a crystal and exploits its unique crystal properties. Here, we use ab initio and classical computer modeling, together with the experiment, to design structures for nanoceria that maximize its nanozymetic activity. We predict that the optimum nanoparticle shape is either a (truncated) polyhedral or a nanocube to expose (active) CeO2{100} surfaces. It should also contain oxygen vacancies and surface hydroxyl species. We also show that the surface structures strongly affect the biological activity of nanoceria. Analogous to catalyst poisoning, phosphorus "poisoning", the interaction of nanoceria with phosphate, a common bodily electrolyte, emanates from phosphate ions binding strongly to CeO2{100} surfaces, inhibiting oxygen capture and release and hence its ability to act as a nanozyme. Conversely, the phosphate interaction with {111} surfaces is weak, and therefore, these surfaces protect the nanozyme against poisoning. The atom-level understanding presented here also illuminates catalytic processes and poisoning in "clean-air" or fuel-cell technologies because the mechanism underpinning and exploited in each technology, oxygen capture, storage, and release, is identical.
Keywords: antioxidant; cerium oxide nanoparticles; density functional theory; enzyme mimetic activity; molecular dynamics; oxidative stress; phosphate; prescription for therapeutic activity.