Redox Activity and Nano–Bio Interactions Determine the Skin Injury Potential of Co₃O₄-Based Metal Oxide Nanoparticles toward Zebrafish

Redox-active metal oxide nanoparticles show varying oxidizing capacities and injury potentials toward biological systems. Here, two metal oxide libraries including transition-metal-doped Co₃O₄ and PdO-Co₃O₄ with strong chemical contacts were design-synthesized and used to investigate their biological injury potential and mechanisms using zebrafish as a model organism. Among different dopants, Cu significantly increased the oxidizing capacity of Co₃O₄. An increased amount of PdO resulted in higher density of heterojunctions, which also led to higher oxidizing capacity. The oxidizing capacity of these nanoparticles was positively correlated with higher mortality of dechorionated embryos and severe larval skin injury upon exposure. Using transgenic zebrafish Tg(LysC:eGFP), we show in real time that the redox-active nanoparticles induced skin injury and activated the infiltration of immune cells. Such inflammatory response was confirmed by the increased mRNA expression level of Nrf2a, HO-1, IL-1β, and IL-6 genes. Although the exposure to the nanoparticles alone was not lethal, the skin injury did lower the tolerance level against other environmental contaminants. More importantly, after withdrawing from the nanoparticle exposure, larvae with skin injury could recover within 24 h in uncontaminated medium, indicating such injury was transient and recoverable.