Macrophage-Mediated Pulmonary Inflammatory Response and Underlying Mechanisms Induced by Lithium Cobalt Oxide Nanoparticles

• • LCO NPs induced significant ROS production and secretion of IL-6, IL-1β, and TNF-α in macrophages, driving M1 polarization, with cobalt ion release as low as 1.03% in water and 0.11% in culture medium, indicating particle-specific toxicity rather than ion-mediated effects. • • Intranasal exposure in mice led to dose-dependent pulmonary accumulation of LCO NPs, with high-dose groups showing systemic cobalt translocation, and histopathology confirmed alveolar destruction and inflammatory cell infiltration, validating acute lung injury. • • Transcriptomic profiling identified significant enrichment of NF-κB, JAK-STAT, and Toll-like receptor signaling pathways, providing mechanistic insight into macrophage activation and inflammatory cascades, though targeted validation is required. • • The study establishes a multi-level toxicity assessment framework (material-cell-organism) that can be applied to evaluate immunotoxicity of other battery materials, supporting occupational exposure limits and safe design strategies.