title: Macrophage silica nanoparticle response is phenotypically dependent.
abstract: Phagocytes are important players in host exposure to nanomaterials. Macrophages in particular are believed to be among the "first responders" and primary cell types that uptake and process nanoparticles, mediating host biological responses by subsequent interactions with inflammatory signaling pathways and immune cells. However, variations in local microenvironmental cues can significantly change the functional and phenotype of these cells, impacting nanoparticle uptake and overall physiological response. Herein we focus on describing the response of specific RAW 264.7 macrophage phenotypes (M1, INF-gamma/LPS induced and M2, IL-4 induced) to Stöber silica nanoparticle exposure in vitro and how this response might correlate with macrophage response to nanoparticles in vivo. It was observed that variations in macrophage phenotype produce significant differences in macrophage morphology, silica nanoparticle uptake and toxicity. High uptake was observed in M1, versus low uptake in M2 cells. M2 cells also displayed more susceptibility to concentration dependent proliferative effects, suggesting potential M1 involvement in in vivo uptake. Nanoparticles accumulated within liver and spleen tissues, with high association with macrophages within these tissues and an overall Th1 response in vivo. Both in vitro and in vivo studies are consistent in demonstrating that silica nanoparticles exhibit high macrophage sequestration, particularly those with Th1/M1 phenotype and in clearance organs. This sequestration and phenotypic response should be a primary consideration when designing new Stöber silica nanoparticle systems, as it might affect the overall efficacy.
authors.affiliation: University of Utah, Department of Bioengineering, 36 S. Wasatch Dr, Salt Lake City, UT 84112, USA; University of Utah, Utah Center for Nanomedicine, Nano Institute of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Herd
authors.affiliation: University of Utah, Department of Bioengineering, 36 S. Wasatch Dr, Salt Lake City, UT 84112, USA; University of Utah, Utah Center for Nanomedicine, Nano Institute of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Kristopher T
authors.initials: KT
authors.lastname: Bartlett
authors.affiliation: University of Utah, Utah Center for Nanomedicine, Nano Institute of Utah, Salt Lake City, UT 84112, USA; University of Utah, Department of Pharmaceutics and Pharmaceutical Chemistry, Salt Lake City, UT 84112, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Gustafson
authors.affiliation: Animal Reference Pathology, P.O. Box 17580, Salt Lake City, UT 84117, USA.
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: McGill
authors.affiliation: University of Utah, Department of Bioengineering, 36 S. Wasatch Dr, Salt Lake City, UT 84112, USA; University of Utah, Utah Center for Nanomedicine, Nano Institute of Utah, Salt Lake City, UT 84112, USA; University of Utah, Department of Pharmaceutics and Pharmaceutical Chemistry, Salt Lake City, UT 84112, USA. Electronic address: hamid.ghandehari@utah.edu.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Ghandehari
mesh_terms: D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D053758:Nanoparticles; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D012822:Silicon Dioxide
keywords: Drug delivery; Macrophage; Nanoparticles; Silica