Catastrophic inflammatory death of monocytes and macrophages by overtaking of a critical dose of endocytosed synthetic amorphous silica nanoparticles/serum protein complexes. (July 2013)

• Record Type: Journal Article
• Authors: Fedeli, Chiara; Selvestrel, Francesco; Tavano, Regina; Segat, Daniela; Mancin, Fabrizio; Papini, Emanuele
• Is Part Of: Nanomedicine. Volume 8:Number 7(2013)
• Page Start: 1101
• Page End: 1126
• Publication Date: 2013-07
• Subjects: amorphous silica -- cell death -- fetal calf serum -- inflammatory cytokines -- LUDOX® SiO2-NPs -- macrophages -- monocytes -- mononuclear phagocyte system -- nanoparticles -- reticular endothelial system -- Stöber SiO2-NPs; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm.12.136
• Languages: English
• ISSNs: 1743-5889

Abstract

Aims: We tested whether phagocytic monocytes/macrophages are more susceptible than nonphagocytes to nanoparticle (NP) toxicity.Materials & methods: We compared in vitro cell death and proinflammatory cytokine production in human monocytes, macrophages, lymphocytes and HeLa cells due to synthetic amorphous silica (SiO2 )-NPs in different serum concentrations and correlated them with cellular uptake and distribution.Results: Phagocytes were approximately ten-times more sensitive than nonphagocytes to SiO2 -NPs and more effectively endocytosed SiO2 -NP–serum protein nanoagglomerates, so determining their accumulation in acidic endocytic compartments well beyond a critical/cytotoxic threshold. Monocyte/macrophage death was paralleled by cytokine secretion.Conclusion: The physiological specialization of monocytes/macrophages to effectively capture NPs may expose them to the risk of catastrophic inflammatory death upon saturation of their maximal storage capacity. Original submitted 9 March 2012; Revised submitted 3 August 2012; Published online 13 December 2012