Modeling the Kinetic Behavior of Reactive Oxygen Species with Cerium Dioxide Nanoparticles

The world of medicinal therapies has been historically, and remains to be, dominated by the use of elegant organic molecular structures. Now, a novel medical treatment is emerging based on CeO₂ nano-crystals that are discrete clusters of a few hundred atoms. This development is generating a great deal of exciting and promising research activity, as evidenced by this Special Issue of Biomolecules. In this paper, we provide both a steady-state and time-dependent mathematical description of a sequence of reactions: superoxide generation, superoxide dismutase, and hydrogen peroxide catalase and ceria regeneration. This sequence describes the reactive oxygen species (ROS); superoxide, O₂^-, molecular oxygen, O₂, hydroxide ion OH^- and hydrogen peroxide, H₂O₂, interacting with the Ce^3+, and Ce⁴⁺ surface cations of nanoparticle ceria, CeO₂. Particular emphasis is placed on the predicted time-dependent role of the Ce³⁺/Ce⁴⁺ ratio within the crystal. The net reaction is succinctly described as: H₂O₂ + 2O₂^- + 2H⁺ → 2H₂O + 2O₂. The chemical equations and mathematical treatment appears to align well with several critical in vivo observations such as; direct and specific superoxide dismutase (SOD), ROS control, catalytic regeneration, ceria self-regulation and self-limiting behavior. However, in contrast to experimental observations, the model predicts that the 4+ ceric ion state is the key SOD agent. Future work is suggested based on these calculations.