Environmental Gating of Cerium Species- versus Contact-Associated Toxicity in Rod-Like Cerium Nanomaterials

How medium chemistry shifts the relative contributions of composition-associated interfacial processes and particle-cell contact remains unresolved. Here we compare morphologically matched rod-like cerium dioxide (CeO₂) and cerium phosphate (CePO₄) against Escherichia coli in organic- and ligand-rich Luria-Bertani broth (LB) and nutrient-free, ligand-poor normal saline (NS). In LB, CePO₄ (100 mg/L) significantly delayed growth (OD₆₀₀ decreased by 16.1% at 3 h) and reduced viability (CFU decreased by 14.7%; Live/Dead decreased by 15.8%), whereas CeO₂ produced no detectable effect at the same dose. Ce L₃-edge XANES with linear-combination fitting of bacterial pellets indicated CePO₄ remained predominantly Ce (III) and showed a minor carboxylate-like proxy contribution (5.7% at 3 h; 9.5% at 6 h), accompanied by a larger operationally defined exchangeable cerium pool (acid-desorbable cerium: 255.5 ± 42.5 μg/L for CePO₄ versus 141.3 ± 23.7 μg/L for CeO₂). In NS, interfacial transformation was curtailed and toxicity increased for both materials, showing enhanced membrane injury consistent with a greater contribution from particle-cell contact under ligand-poor conditions. Proteomics and a conditional single-ion membrane simulation support the plausibility that hydrated Ce(III), if present at the bacterial interface, can coordinate outer-membrane phosphate groups, linking interfacial cerium availability to stress phenotypes. Together, these results show that medium chemistry shifts the relative contributions of cerium species-associated and particle-contact-associated processes, informing safer-by-design cerium nanomaterials and more realistic antibacterial testing frameworks.