title: Effect of silica and gold nanoparticles on macrophage proliferation, activation markers, cytokine production, and phagocytosis in vitro.
abstract: The accumulation of durable nanoparticles (NPs) in macrophages following systemic administration is well described. The ultimate biological impact of this accumulation on macrophage function, however, is not fully understood. In this study, nontoxic doses of two durable NPs, SiO2 and Au, at particle sizes of ~10 nm and 300 nm were used to evaluate the effect of bioaccumulation on macrophage function in vitro using RAW 264.7 mouse macrophage-like cells as a model system. Cell proliferation, cell cycle, cytokine production, surface marker activation, and phagocytosis responses were evaluated through a panel of assays using flow cytometry and confocal microscopy. The most dramatic change in RAW 264.7 cell function was a reduction in phagocytosis as monitored by the uptake of Escherichia coli. Cells exposed to both 10 nm Au NPs and 10 nm SiO2 NPs showed ~50% decrease in phagocytosis, while the larger NPs caused a less dramatic reduction. In addition to modifying phagocytosis profiles, 10 nm SiO2 NPs caused changes in proliferation, cell cycle, and cell morphology. Au NPs had no effect on cell cycle, cytokine production, or surface markers and caused interference in phagocytosis in the form of quenching when the assay was performed via flow cytometry. Confocal microscopy analysis was used to minimize this interference and demonstrated that both sizes of Au NPs decreased the phagocytosis of E. coli. Overall, our results demonstrate that Au and SiO2 NP uptake by macrophages can influence macrophage phagocytosis in vitro without altering surface markers and cytokine production in vitro. While the biological impact of these findings remains unclear, our results indicate that bioaccumulation of durable NPs within the macrophages may lead to a suppression of bacterial uptake and possibly impair bactericidal activity.
authors.affiliation: Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Simona
authors.initials: S
authors.lastname: Bancos
authors.affiliation: Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Stevens
authors.affiliation: Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Tyner
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D006046:Gold / Q000737:chemistry*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects*; D000067996:RAW 264.7 Cells; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D016207:Cytokines; D006046:Gold; D012822:Silicon Dioxide
keywords: bioaccumulation; gold nanoparticles; macrophage function; phagocytosis; silica nanoparticles