Long-term exposure to nanoparticles alters senescence-associated markers and immune responses in human monocyte-derived macrophages

Abstract

Background: Macrophages are essential in maintaining tissue homeostasis. However, their functionality and phenotype can be impaired by senescence, which impacts immune competence and inflammatory responses. Despite the growing use of engineered nanoparticles (NPs) in biomedical applications or chronic exposure to environmental NPs, their impact on macrophage senescence and immune function remains poorly understood, particularly in the context of prolonged NP exposure. Results: Here, we first confirm that human monocyte-derived macrophages (MDMs) undergo senescence in vitro, as indicated by a panel of senescence-associated markers that increased within 10 days of culture. Then, we investigate how gold (AuNPs), silica (SiO₂ NPs), and polyethylene terephthalate (PET NPs) influence senescence-associated markers, and immunocompetence in MDMs. By examining key markers such as senescence-associated beta-galactosidase (SA-β-gal), CDKN2A (p16), and senescence-associated secretory phenotype (SASP) cytokines, e.g., interleukin (IL)-6 and IL-8, over extended exposure periods up to 10 days, we revealed material-specific effects: AuNPs induce a strong pro-inflammatory response, SiO₂ NPs demonstrate low inflammatory potential, and PET NPs modulate the gene expression level of CDKN2A involved in cell cycle regulation. Conclusion: Our findings underscore the need to characterize long-term NP behavior in biological systems and reveal material-specific effects on macrophage senescence-associated traits and immune function. Rather than assessing NP-induced senescence, this study defines how prolonged NP exposure modulates selected senescence-associated signatures in non-proliferative macrophages, offering valuable insights into the functional consequences of chronic NP accumulation.