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Monocytes/macrophages are essential in innate immune response against pathogens also because their ability to release extracellular traps named METs (monocytes/macrophages extracellular traps). These structures are composed of DNA fibers decorated with nuclear and cytoplasmic proteins and their production process is called METosis. In this study attention has been focused on the ability of differently charged molecular systems (polyhedral oligomeric silsesquioxanes, POSS positively or negatively charged) to induce METosis.METs formation was induced by lipopolysaccharide (250 μg/ml, positive control) and POSS positive and negative (0.05–1 mg/ml) treatment. METs were visualized and quantified by confocal microscopy using Sytox green staining. Oxidative stress, autophagy, as well as endocytosis involvement in the POSS induced METosis was evaluated.Results obtained indicate a POSS positive or negative dose dependent ability in inducing MET release independently to their charge and that this phenomenon is a consequence of POSS +/− internalization. Moreover, studies using many reactive oxidative species (ROS) blockers and autophagy inhibitor showed a strong reduction in POSS induced METosis indicating their involvement.POSS +/− induce extracellular traps production in human monocytes/macrophages by oxidative and autophagic pathway.