Key Takeaways & Executive Findings
- •• • 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.
Abstract
Lithium cobalt oxide (LCO) nanoparticles (NPs), generated during the lifecycle of LCO batteries via mechanical wear, pose respiratory health risks. This study systematically assessed LCO NPs' physicochemical properties, ion release, and immunotoxicity using multi-scale models. LCO NPs exhibited irregular morphology, layered crystal structure, good dispersion, and negative surface charge. Cobalt ion release was minimal: 1.03% in deionized water and 0.11% in cell culture medium. In vitro, LCO NPs significantly induced reactive oxygen species (ROS) production and secretion of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) in macrophages, promoting M1 polarization. In vivo, intranasal exposure caused dose-dependent pulmonary accumulation, alveolar destruction, inflammatory cell infiltration, and elevated cytokines in bronchoalveolar lavage fluid (BALF). Transcriptomic analysis revealed significant enrichment of NF-κB, JAK-STAT, and Toll-like receptor signaling pathways, implicating these in macrophage activation and inflammation amplification. This multi-level study elucidates LCO NPs' immunotoxicity mechanisms, providing a scientific basis for environmental health risk assessment and management of lithium-ion battery materials.
1. Introduction
The proliferation of lithium cobalt oxide (LCO) batteries in portable electronics and electric vehicles has raised concerns about occupational and environmental exposure to LCO nanoparticles (NPs). During production, use, and recycling, mechanical wear generates nano-sized particles that can be inhaled, yet systematic studies on their pulmonary immunotoxicity are scarce. Existing toxicological assessments often focus on soluble metal ions, but LCO NPs exhibit low ion release, suggesting particle-specific effects that are poorly understood. This knowledge gap hinders accurate risk assessment and the development of safety guidelines for battery material handling.
This study addresses the bottleneck by employing a comprehensive multi-scale toxicity assessment framework, integrating physicochemical characterization, in vitro macrophage assays, in vivo murine models, and transcriptomic analysis. By quantifying ion release, inflammatory cytokine secretion, and signaling pathway activation, the research delineates the molecular mechanisms underlying LCO NP-induced lung inflammation. The findings provide critical data for regulatory bodies and industry stakeholders, enabling evidence-based occupational exposure limits and the design of safer battery materials.
Loading authentic research manuscript (Pages 1–5)...
ZHAO Xinglin, ZHANG Zhenyong, ZHANG Kena, CHEN Yangsheng, LIU Yin, ZHAO Bin (2026). Macrophage-Mediated Pulmonary Inflammatory Response and Underlying Mechanisms Induced by Lithium Cobalt Oxide Nanoparticles. Environmental Chemistry. https://doi.org/10.7524/j.issn.0254-6108.2026021301
Research & Educational Purpose Only: The translations, structured abstracts, analytical annotations, and data reports provided by SinoGreenTechare intended exclusively for academic research, internal corporate R&D, and educational benchmarking. They do not constitute formal engineering, chemical safety, legal, or professional advice.
Copyright & Intellectual Property Notice: Original copyright of the underlying source articles and experimental data remains with the respective authors, institutions, and original publishing journals. SinoGreenTech claims intellectual property only over its proprietary translations, analytical syntheses, and AEO structured enhancements in accordance with international fair use and academic citation principles.
Frequently Asked Questions
What is the dissolution rate of cobalt ions from LCO NPs in biological media, and how does this influence the interpretation of toxicity results?
The dissolution rate is minimal: 1.03% in deionized water and 0.11% in cell culture medium. This low ion release suggests that the observed toxicity is primarily due to particle-specific effects rather than soluble cobalt ions, which is critical for risk assessment and regulatory classification.
Which signaling pathways are activated by LCO NPs, and what is the evidence for their involvement?
Transcriptomic analysis revealed significant enrichment of NF-κB, JAK-STAT, and Toll-like receptor signaling pathways. These pathways are known regulators of inflammation and macrophage polarization. However, the study notes that these are high-throughput screening results, and targeted validation (e.g., qPCR, Western blot, inhibitor studies) is needed to confirm their functional roles.
What are the key pathological features observed in mice after intranasal exposure to LCO NPs?
Mice exhibited dose-dependent pulmonary accumulation of LCO NPs, with high-dose groups showing systemic cobalt translocation. Histopathology revealed alveolar structure destruction and inflammatory cell infiltration, and BALF levels of IL-6, IL-1β, and TNF-α were significantly elevated, confirming acute lung inflammation.
How does this study contribute to the environmental health risk assessment of lithium-ion battery materials?
By providing a multi-level toxicity assessment framework, the study offers mechanistic insights into LCO NP immunotoxicity, which is essential for setting occupational exposure limits and developing safer battery materials. The low ion release and particle-driven effects underscore the need for particle-specific risk assessment strategies.
What are the limitations of this study, and what future research directions are suggested?
The transcriptomic findings are high-throughput and require targeted validation. Future studies should employ pathway inhibitors or gene knockout models to confirm the causal roles of NF-κB, JAK-STAT, and TLR pathways. Additionally, chronic exposure studies and assessments of other battery materials are recommended.
Related Chinese Research & Cross-Citations
Exploring the Potential Molecular Mechanisms of Eight Environmental Pollutants in Lung Adenocarcinoma through Network Toxicology, Machine Learning, and Multi-Omics Analysis
Epidemiological studies have established a significant association between exposure to environmental pollutants (EP) and the risk of lung adenocarcinoma (LUAD). This study integrates network toxicology and multi-omics analysis to elucidate the EP-LUAD molecular regulatory network and identify key regulatory genes, thereby revealing novel mechanisms of environmental carcinogenesis. Transcriptomic data from GEO and TCGA databases yielded 4,971 and 4,488 disease-related targets, respectively. Integration of toxicology databases (TargetNet, Swiss Target Prediction, CTD, SEA) identified 24,860 potential targets for eight common pollutants (SO2, NO, CO, NO2, O3, benzene, toluene, and polycyclic aromatic hydrocarbons). Intersection of these datasets produced 1,536 EP-LUAD common target genes. Protein-protein interaction network analysis identified 247 core targets. Machine learning selected five key genes: AGER, CAV1, CD44, CEP55, and GNB3, which demonstrated robust diagnostic and prognostic efficacy. Their expression correlated with immune cell infiltration, including CD4+ memory T cells and macrophages. Single-cell RNA sequencing revealed epithelial cell-specific expression patterns. Molecular docking confirmed stable pollutant-target binding, with PAH showing highest affinity for CD44 (binding energy −9.32 kcal·mol−1) and GNB3 (−8.32 kcal·mol−1). These findings establish AGER, CAV1, CD44, CEP55, and GNB3 as core molecular mediators of pollution-related LUAD. The high-affinity binding of PAH to CD44 and GNB3 underscores its carcinogenic potential. This study constructs a multi-level regulatory network for EP-LUAD, revealing underlying molecular mechanisms and providing novel potential targets and theoretical basis for early warning and intervention.
Effects of Different Functionalized Nanoplastics on the Transformation of Extracellular Antibiotic Resistance Genes in Aquatic Environments
The rapid dissemination of antibiotic resistance genes (ARGs) in aquatic environments poses serious threats to public health and environmental safety under the 'One Health' framework. Nanoplastics (NPs), as co-occurring pollutants, can exacerbate ARG risks by promoting horizontal gene transfer (HGT), yet the influence of different functional groups on extracellular ARG (eARG) transformation remains unclear. This study investigated the effects of carboxy-modified polystyrene NPs (PS-COOH) and amino-functionalized polystyrene NPs (PS-NH2) compared to unmodified polystyrene NPs (PS) on the transformation of the extracellular resistance plasmid IE-V1955 (carrying an ampicillin resistance gene) into Escherichia coli DH5α. Results showed that PS-COOH exposure promoted plasmid transformation similarly to PS, with effects increasing over 0.1–20 mg·L−1. Low concentrations (0.1–0.5 mg·L−1) of PS-NH2 also enhanced transformation, with stronger effects than PS-COOH at equal doses, whereas high concentrations (1–20 mg·L−1) inhibited it. Mechanistically, PS-COOH (0.1–20 mg·L−1) and low PS-NH2 induced intracellular reactive oxygen species (ROS), increased cell membrane permeability, elevated the protein-to-polysaccharide ratio in extracellular polymeric substances (EPS), and promoted biofilm formation, thereby facilitating transformation. High PS-NH2 concentrations caused excessive ROS leading to cell lysis and formed aggregates with plasmids larger than membrane pores, blocking uptake. These findings provide a theoretical basis for assessing the combined environmental health risks of NPs and ARGs.
Cardiovascular Toxicity Induced by Micro/Nano-Plastics and Its Mechanisms
Micro/nano-plastics (MNPs) are emerging contaminants widely detected in human circulatory systems, including blood, heart, and vascular endothelium, raising concerns about cardiovascular health risks. This systematic review analyzed 61 peer-reviewed studies (2008–2024) to elucidate the cardiotoxic effects and molecular mechanisms of MNPs. Evidence indicates that MNPs exposure elevates risks of atherosclerosis, thrombosis, and arrhythmias through oxidative stress, inflammatory cascades, endothelial dysfunction, and metabolic dysregulation. Notably, co-exposure with persistent organic pollutants (POPs) or heavy metals may produce synergistic or antagonistic effects. Current research relies predominantly on animal and cell models, with critical gaps in low-dose, long-term exposure data and epidemiological evidence. Future studies should optimize experimental designs, integrate metabolomics and epigenetics, and explore transgenerational effects and combined toxicity mechanisms to inform pollution control policies and mitigate cardiovascular risks.
Body Burden of Polybrominated Diphenyl Ethers and Joint Effects on Thyroid Function in a Physical Examination Population in Shenzhen
This study characterized the body burden of polybrominated diphenyl ethers (PBDEs) in a physical examination population in Shenzhen and evaluated its impact on thyroid function. Serum samples from 368 residents were analyzed for eight PBDE congeners using atmospheric pressure gas chromatography-tandem mass spectrometry (APGC-MS/MS). The median concentration of ∑8PBDEs was 10.2 ng·g⁻¹ lipid weight (lw), ranging from 0.13 to 2089.4 ng·g⁻¹ lw, with BDE-209 predominating (59.7% of total). Multiple linear regression revealed that a 1.7-fold increase in serum BDE-153 was associated with a 0.4% increase in free triiodothyronine (FT3) (P<0.05), while a 1.7-fold increase in BDE-183 was associated with a 0.9% decrease in total triiodothyronine (T3) and a 0.7% decrease in FT3 (P<0.05). Bayesian kernel machine regression (BKMR) indicated a negative correlation between mixed PBDE exposure and thyroid-stimulating hormone (TSH) at high exposure levels. Weighted quantile sum (WQS) regression showed that mixed exposure was associated with decreased T3 levels and T3/FT3 ratio, with BDE-153 and BDE-183 as the primary contributors. These findings suggest that PBDE exposure may adversely affect thyroid function and disrupt thyroid hormone homeostasis, with BDE-183 and BDE-153 playing key roles. This study provides a scientific basis for PBDE health risk assessment and thyroid protection.
Mechanisms of Natural Organic Matter in Regulating Microplastic Aggregation and Transport in Soil-Groundwater Systems: A Review
Microplastics (MPs) are persistent emerging contaminants ubiquitously distributed in soil-groundwater environments, where their aggregation and transport critically govern pollutant fate and ecological risks. Natural organic matter (NOM), a complex assemblage of organic compounds, interacts with MPs and porous media via hydrogen bonding, π-π interactions, hydrophobic effects, and electrostatic binding, thereby modulating MP surface properties and environmental behavior. This review systematically synthesizes the mechanisms by which NOM influences MP aggregation and transport, with emphasis on the distinct roles of humic substances, proteins, and extracellular polymeric substances (EPS), and their synergistic modulation with solution chemistry (pH, ionic strength, ion type). Additionally, NOM accelerates MP aging and alters surface characteristics, consequently impacting transport capacity. Current research limitations are identified, and future directions are proposed to inform MP pollution risk assessment and management strategies. Key findings indicate that NOM generally enhances MP stability and mobility at low ionic strengths, while high ionic strengths may induce aggregation depending on NOM type and ion valence. Humic substances predominantly increase electrostatic repulsion, whereas proteins and EPS can bridge particles, promoting aggregation. Aging processes, accelerated by NOM photochemical activity, increase surface oxygen functionality and hydrophilicity, further altering transport. The review underscores the need for systematic studies under environmentally relevant conditions to predict MP fate accurately.
Neurotoxicity of Carboxyl-Modified Polystyrene Microplastics on Zebrafish at Early Developmental Stage
Carboxyl-modified polystyrene microplastics (PS-COOH) are negatively charged particles formed by surface oxidation and functional group modification of polystyrene microplastics (PS), widely used in biomedical and analytical chemistry. However, studies on their neurotoxic effects on aquatic organisms are scarce. This study employed zebrafish (Danio rerio) as a model organism, exposing embryos to environmentally relevant concentrations (0.1, 1, 10, 100 μg·L−1) of PS and PS-COOH. Neurotoxic effects were assessed by measuring tail coiling frequency at 24 hpf and swimming velocity under alternating light/dark cycles at 120 hpf. Results demonstrated that both PS and PS-COOH induced neurotoxicity, with PS-COOH significantly reducing tail coiling frequency and average swimming speed compared to PS (P<0.05). Exposure to 10 μg·L−1 PS-COOH disrupted neurotransmitter homeostasis, altering levels of acetylcholine (ACh), serotonin (5-HT), and γ-aminobutyric acid (GABA). Transgenic zebrafish Tg(huc:EGFP) fluorescence assays revealed that PS-COOH (0.1–100 μg·L−1) caused damage to central neurons. These findings indicate that PS-COOH exposure impairs cholinergic, serotonergic, and GABAergic neurotransmission, induces neuronal damage, and exerts neurotoxic effects on zebrafish larvae. This study provides a theoretical basis for assessing the ecological and health risks of modified microplastics.