Untangling the biological effects of cerium oxide nanoparticles: The role of surface valence states

Cerium oxide nanoparticles (nanoceria; CNPs) have been found to have both pro-oxidant and antioxidant effects on different cell systems or organisms. In order to untangle the mechanisms which underlie the biological activity of nanoceria, we have studied the effect of five different CNPs on a model relevant aquatic microorganism. Neither shape, concentration, synthesis method, surface charge (ζ-potential), nor nominal size had any influence in the observed biological activity. The main driver of toxicity was found to be the percentage of surface content of Ce3+ sites: CNP1 (58%) and CNP5 (40%) were found to be toxic whereas CNP2 (28%), CNP3 (36%) and CNP4 (26%) were found to be non-toxic. The colloidal stability and redox chemistry of the most and least toxic CNPs, CNP1 and CNP2, respectively, were modified by incubation with iron and phosphate buffers. Blocking surface Ce3+ sites of the most toxic CNP, CNP1, with phosphate treatment reverted toxicity and stimulated growth. Colloidal destabilization with Fe treatment only increased toxicity of CNP1. The results of this study are relevant in the understanding of the main drivers of biological activity of nanoceria and to define global descriptors of engineered nanoparticles (ENPs) bioactivity which may be useful in safer-by-design strategies of nanomaterialsThis research was supported by CTM2013-45775-C2-1-R and CTM2013-45775-C2-2-R grants from MINECO, the Dirección General de Universidades e Investigación de la Comunidad de Madrid, Research Network S2013/MAE-2716 and National Science Foundation for Nanotechnology Research (EECS – 0901503, CBET-1261956). Gerardo Pulido-Reyes thanks the Spanish Ministry of Education for the award of an FPU grant