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

ABSTRACT

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 Co ^{2 +} 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.