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However, the underlying molecular mechanisms behind NPP induced immune cell (monocyte\/macrophage) toxicity and their relationship with existing pathological conditions remain largely unexplored. The current study explored the interaction of NPPs with serum proteins and composition of protein corona through proteomic analysis (LC\u2010HRMS\/MS). Further, we investigated the immunotoxic effects on THP\u20101 macrophage cells via various cellular and molecular assays, including cytotoxicity, oxidative stress, mitochondrial function, intracellular calcium homeostasis, apoptosis and stress signaling pathway assessment. This study further assessed the amplification potential of NPPs on inflammatory (TNF \u03b1 and lipopolysaccharide), atherogenic (ox\u2010LDL) and environmental (polycyclic aromatic hydrocarbons (PAH)) stress conditions. The findings demonstrated that NPPs triggered cytotoxicity in a dose dependent manner along with excessive ROS generation, mitochondrial impairment, elevated intracellular calcium levels and apoptosis by altering BAX and BCL2 expression. We also found that NPPs activated stress signaling pathways through modulating HSP27, SAPK\/JNK, p38 MAPK and c\u2010Jun phosphorylation. Interestingly, pathway inhibition studies confirmed the involvement of p38 MAPK, ERK and mitochondrial ROS signaling in NPP\u2010associated toxicity. In addition, NPPs exposure augmented inflammatory response, promoted atherogenesis (foam cell formation), amplified PAH induced toxicity. Together, these observations revealed precise adverse outcome pathways (AoP) and stress amplification effects of NPPs on macrophages and consequent toxic effects on the immune system.<\/jats:p>","DOI":"10.1002\/jbt.71103","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:52:47Z","timestamp":1788245567000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nanoplastic Particle Exposure Induces Toxicity and Amplifies Cellular Stress in THP\u20101 Macrophages: Insights on Molecular Pathways and Circulating Proteome Interaction"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8600-7753","authenticated-orcid":false,"given":"Balamurali","family":"Mahalakshmi","sequence":"first","affiliation":[{"name":"Environmental Health and Toxicology Laboratory, Department of Environmental Sciences School of Life Sciences Bharathiar University Coimbatore Tamil 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