Nanoplastics Impair Neuroimmune Integrity Via Cellular Retention and Multiple Organelle Stress

The biological persistence of nanoplastics (NPs) has raised growing concern regarding their potential to accumulate in human tissues yet their impact on neuroimmune cellular function remains largely undefined. Here, we investigated the neuroimmune effects of polystyrene NPs (100, 200, and 1000nm; 10 and 100μg/mL) across neuronal (SH-SY5Y, PCNs) and immune cells (THP1, macrophages). Cellular responses were assessed through analyses of cytotoxicity, immunocytochemistry and cytokine profiling. NPs exposure did not induce acute cytotoxicity but promoted persistent intracellular retention accompanied by lysosomal dysfunction, dysregulated autophagic flux, ER stress, and constrained mitochondrial function, thereby inducing a sublethal multi-organelle stress response. Macrophages exhibited greater vulnerability consistent with phagocytic burden, while inflammatory challenge further enhanced NPs uptake, reinforcing intracellular persistence. In contrast, neurons showed limited extracellular cytokine secretion yet accumulated intracellular IL-1β, suggesting low-grade inflammatory activation. Such responses were recapitulated in PCNs, supporting translational relevance across neuronal models. The cumulative nature of these observations suggests that NPs exposure may give rise to previously unrecognized accumulation-related pathologies, a phenomenon we term "plasticoma" as a conceptual framework, to describe the preferential deposition of non-degradable plastic particles within cells, to frame and stimulate future investigations into NP accumulation and pathology. These findings position NPs as potential determinant of neuroimmune dysfunction and highlight the importance of strategies aimed at mitigating their biological accumulation.