title: Silver nanoparticles compromise neurodevelopment in PC12 cells: critical contributions of silver ion, particle size, coating, and composition.
abstract: BACKGROUND
  Silver exposures are rising because of the increased use of silver nanoparticles (AgNPs) in consumer products. The monovalent silver ion (Ag+) impairs neurodevelopment in PC12 cells and zebrafish.
  
  
  OBJECTIVE
  We compared the effects of AgNPs with Ag+ in PC12 cells for neurodevelopmental end points including cell replication, oxidative stress, cell viability, and differentiation. First, we compared citrate-coated AgNPs (AgNP-Cs) with Ag+, and then we assessed the roles of particle size, coating, and composition by comparing AgNP-C with two different sizes of polyvinylpyrrolidone-coated AgNPs (AgNP-PVPs) or silica nanoparticles.
  
  
  RESULTS
  In undifferentiated cells, AgNP-C impaired DNA synthesis, but to a lesser extent than an equivalent nominal concentration of Ag+, whereas AgNP-C and Ag+ were equally effective against protein synthesis; there was little or no oxidative stress or loss of viability due to AgNP-C. In contrast, in differentiating cells, AgNP-C evoked robust oxidative stress and impaired differentiation into the acetylcholine phenotype. Although the effects of AgNP-PVP showed similarities to those of AgNP-C, we also found significant differences in potencies and differentiation outcomes that depended both on particle size and coating. None of the effects reflected simple physical attributes of nanoparticles, separate from composition or coating, as equivalent concentrations of silica nanoparticles had no detectable effects.
  
  
  CONCLUSIONS
  AgNP exposure impairs neurodevelopment in PC12 cells. Further, AgNP effects are distinct from those of Ag+ alone and depend on size and coating, indicating that AgNP effects are not due simply to the release of Ag+ into the surrounding environment.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Powers
authors.forename: Appala R
authors.initials: AR
authors.lastname: Badireddy
authors.forename: Ian T
authors.initials: IT
authors.lastname: Ryde
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: Seidler
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Slotkin
mesh_terms: D000818:Animals; D002414:Cations, Monovalent / Q000737:chemistry / Q000633:toxicity; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002490:Central Nervous System; D048788:Growth and Development / Q000187:drug effects*; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress; D016716:PC12 Cells; D010316:Particle Size; D051381:Rats; D012834:Silver / Q000737:chemistry / Q000633:toxicity*; D015027:Zebrafish / Q000254:growth & development
chemical_list: D002414:Cations, Monovalent; D012834:Silver