title: RNAi-mediated inhibition of apoptosis fails to prevent cationic nanoparticle-induced cell death in cultured cells.
abstract: BACKGROUND
  Nanoparticles are increasingly being considered as a novel and potent tool for drug delivery, and, therefore, concerns regarding the safety of their use in humans are pertinent. It has been shown that nanoparticles displaying unsaturated amines at their surface are toxic to cells, but the molecular and cellular mechanisms elicited in this response have yet to be described.
  
  
  OBJECTIVE
  In this work we identify key proteins involved in the cytotoxicity of amine-modified polystyrene nanoparticles. We also demonstrate the suitability of RNAi to provide a molecular description of how nanoparticles and cells interact.
  
  
  METHODS
  We have used a focused RNAi strategy in 1321N1 cells to identify key proteins involved in the cytotoxicity induced by amine-modified polystyrene nanoparticles.
  
  
  RESULTS
  We show that the apoptosome is central to the observed mechanism of toxicity and that, although the proapoptotic proteins BAX, BAK, BID, BIM and PUMA are critical modulators of the process, their cellular depletion is insufficient to protect cells from nanoparticle-induced cell death.
  
  
  CONCLUSIONS
  We conclude that the apoptosome, together with proapoptotic proteins of the Bcl-2 family of proteins, is central to amine-modified polystyrene nanoparticle-induced cell death. We further demonstrate that RNAi is a powerful and suitable tool to study the effects of nanoparticles on cellular processes, in particular apoptosis.
authors.affiliation: School of Biology & Environmental Science & Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Dublin 4, Ireland.
authors.forename: Mariana G
authors.initials: MG
authors.lastname: Bexiga
authors.forename: Ciara
authors.initials: C
authors.lastname: Kelly
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Dawson
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Simpson
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002412:Cations / Q000737:chemistry*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species
chemical_list: D000588:Amines; D002412:Cations; D011137:Polystyrenes; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D053148:Caspase 3; D053179:Caspase 7
keywords: RNAi; apoptosis; caspase; cationic nanoparticle; nanotoxicity