Open AccessRNAi-mediated inhibition of apoptosis fails to prevent cationic nanoparticle-induced cell death in cultured cells
Author(s) -
Mariana G. Bexiga,
Ciara Kelly,
Kenneth A. Dawson,
Jeremy C. Simpson
Publication year - 2014
Publication title -
nanomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 109
eISSN - 1748-6963
pISSN - 1743-5889
DOI - 10.2217/nnm.13.151
Subject(s) - programmed cell death , cytotoxicity , apoptosis , microbiology and biotechnology , nanotoxicology , rna interference , chemistry , cell , endocytosis , nanoparticle , biology , in vitro , biochemistry , nanotechnology , materials science , rna , gene
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. Aims: 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. Materials & 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. Conclusion: 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. Original submitted 18 March 2013; Revised submitted 22 July 2013