pH-Responsive Morphology-Controlled Redox Behavior and Cellular Uptake of Nanoceria in Fibrosarcoma

The present work reports structural/microstructural correlations with biological performance for three nanoceria morphologies, aiming to elucidate the major factors in their interactions with fibrosarcoma. These include the pH of the in vitro medium and the crystallinities, stoichiometries, surface areas and chemistries, and maximal oxygen vacancy concentrations ([V_O^••]_Max). Although the [V_O^••]_Max is dominant in the redox behavior, the role of the morphology was manifested in the order of effectiveness of the redox regulation, which was nanocubes (NC) < nanorods (NR) < nanooctahedra (NO). The proposed mechanism illustrates the role of V_O^•• in explaining antioxidant behavior at physiological pH 7.4 and prooxidant behavior in the tumor microenvironment pH 6.4. Cellular uptake at pH 7.4 was dominated by the morphology of the nanoparticle, demonstrating the order NO < NC < NR. Control of the [V_O^••]_Max, morphology, and dependent structural and microstructural parameters can be used to optimize the uptake and redox performance of nanoceria.