title: Evaluation of endocytosis of silica particles used in biodegradable implants in the brain.
abstract: Silica nanoparticles embedded in a biodegradable scaffold have been proposed to offer several advantages when used in laser-tissue-soldering of blood vessels in the brain. During degradation, these nanoparticles are likely to be released into the surrounding brain tissue. The aim of this study was to investigate possible cellular uptake mechanism(s) of the two silica nanoparticle types in microglial cells as well as their effect on autophagy and inflammatory cytokines. The nanoparticle uptake was analysed quantitatively using high-content analysis. Nanoparticle incubation did not modulate cytokine secretion and autophagy at any time point investigated. The nanoparticles were taken up by the microglia cells in a time- and particle-dependent manner. The maximal uptake was reached after 4hours and the nanoparticles were found in the endoplasmic reticulum and lysosomes. Macropinocytosis and phagocytosis were predominantly responsible for the uptake, whereas clathrin- and caveolin-independent endocytosis were involved to a minor extent.
authors.affiliation: Veterinary Pharmacology and Toxicology, Department Clinical Research and Veterinary Public Health, Vetsuisse Faculty University Bern, Bern, Switzerland.
authors.forename: Jana
authors.initials: J
authors.lastname: Zielinski
authors.affiliation: Veterinary Pharmacology and Toxicology, Department Clinical Research and Veterinary Public Health, Vetsuisse Faculty University Bern, Bern, Switzerland; Institute of Applied Physics, University Bern, Bern, Switzerland.
authors.forename: Anja-Maria
authors.initials: AM
authors.lastname: Möller
authors.affiliation: Institute of Applied Physics, University Bern, Bern, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Frenz
authors.affiliation: Veterinary Pharmacology and Toxicology, Department Clinical Research and Veterinary Public Health, Vetsuisse Faculty University Bern, Bern, Switzerland. Electronic address: meike.mevissen@vetsuisse.unibe.ch.
authors.forename: Meike
authors.initials: M
authors.lastname: Mevissen
mesh_terms: D020341:Absorbable Implants; D001921:Brain; D002966:Clathrin; D004705:Endocytosis; D006801:Humans; D053758:Nanoparticles; D012822:Silicon Dioxide / Q000493:pharmacokinetics*
chemical_list: D002966:Clathrin; D012822:Silicon Dioxide
keywords: High-content analysis; Microglia; Nanoparticles; Uptake mechanism