Decoupling Ion Release from Biointerface Persistence in Redox-Active Cobalt Nanoparticle Toxicity in a Zebrafish Model.

Redox-active nanomaterials derive important functional properties from surface-mediated electron transfer, yet chemical stabilization is commonly assumed to reduce biological hazards by suppressing oxidation and metal-ion release. Here, we tested this assumption using a chemically matched series of cobalt-gold nanoparticles (Co-AuNPs) with increasing surface complexity: exposed gold nanoflowers (NFLs), citrate-capped Co-Au core-shell nanoparticles, and hybrid lipid membrane (HLM)-coated Co-AuNPs. Increasing surface passivation reduced oxidative dissolution and Co2 + release under both chemical and physiological conditions. However, zebrafish embryo assays revealed a persistence-dominated exposure regime in which the most chemically stabilized nanoparticles produced the strongest toxic response. Citrate-capped NFLs exhibited the highest ICP-MS-measured dissolved cobalt concentrations but showed lower toxicity, whereas HLM-coated Co-AuNPs exhibited substantially lower dissolved cobalt despite producing greater developmental toxicity. These findings show that dissolved cobalt alone does not account for biological effects. Citrate-capped Co-AuNPs further demonstrate that dispersion stability alone is also insufficient to predict toxicity. Instead, the results support a model in which sustained biointerface persistence contributes substantially to toxicity when dissolution is suppressed.