title: Cellular entry of nanoparticles via serum sensitive clathrin-mediated endocytosis, and plasma membrane permeabilization.
abstract: Increasing production and application of nanomaterials raises significant questions regarding the potential for cellular entry and toxicity of nanoparticles. It was observed that the presence of serum reduces the cellular association of 20 nm carboxylate-modified fluorescent polystyrene beads up to 20-fold, relative to cells incubated in serum-free media. Analysis by confocal microscopy demonstrated that the presence of serum greatly reduces the cell surface association of nanoparticles, as well as the potential for internalization. However, both in the presence and absence of serum, nanoparticle entry depends upon clathrin-mediated endocytosis. Finally, experiments performed with cells cooled to 4°C suggest that a proportion of the accumulation of nanoparticles in cells was likely due to direct permeabilization of the plasma membrane.
authors.affiliation: Physical Sciences of Imaging for the Biomedical Sciences (PSIBS) Doctoral Training Center, School of Chemistry, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Smith
authors.forename: Maude
authors.initials: M
authors.lastname: Giroud
authors.forename: Helen L
authors.initials: HL
authors.lastname: Wiggins
authors.forename: Florence
authors.initials: F
authors.lastname: Gower
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Thorley
authors.forename: Bjorn
authors.initials: B
authors.lastname: Stolpe
authors.forename: Julie
authors.initials: J
authors.lastname: Mazzolini
authors.forename: Rosemary J
authors.initials: RJ
authors.lastname: Dyson
authors.forename: Joshua Z
authors.initials: JZ
authors.lastname: Rappoport
mesh_terms: D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002966:Clathrin / Q000378:metabolism*; D016895:Culture Media, Serum-Free; D004285:Dogs; D004705:Endocytosis; D005456:Fluorescent Dyes; D006367:HeLa Cells; D006801:Humans; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage* / Q000633:toxicity*; D014168:Transferrin / Q000378:metabolism
chemical_list: D002966:Clathrin; D016895:Culture Media, Serum-Free; D005456:Fluorescent Dyes; D014168:Transferrin