From Carriers to Mitigators: Environmental Aging Unexpectedly Transforms Nanoplastics into Limiters of Cadmium Bioavailability in Osteoblasts

Nanoplastics are generally regarded as exacerbating heavy metal toxicity by acting as Trojan horse carriers of metal ions. Here, we demonstrate that aged polystyrene nanoplastics (PS-NPs) unexpectedly mitigate cadmium [Cd(II)]-induced acute cytotoxicity in osteoblasts, suggesting a modulatory role beyond passive transport. Aged PS-NPs effectively adsorb Cd(II) via electrostatic and coordination interactions, forming larger aggregates that significantly limit cellular uptake compared to free Cd(II). This mitigating effect was further associated with restricted Cd(II) release, altered subcellular trafficking, and limited mitochondrial penetration, as revealed by super-resolution structured illumination microscopy (SIM). In addition, molecular-level analyses demonstrated that aged PS-NPs impaired Cd(II) binding to biomolecules. Collectively, these mechanisms reduced Cd(II) bioavailability. Quantitatively, aged PS-NPs reduced intracellular free Cd(II) by ∼14-29% and attenuated cytotoxic responses by ∼15-33% with respect to oxidative stress, membrane damage, and apoptosis during 24 h of acute co-exposure. Our findings reveal an unexpected mitigating role of aged nanoplastics in metal toxicity, challenging their conventional view as merely passive carriers. However, given the environmental persistence of both nanoplastics and Cd(II), their long-term co-exposure risks warrant urgent assessment.