Journal
NANOMEDICINE
Volume 9, Issue 11, Pages 1651-1664Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/NNM.13.151
Keywords
apoptosis; caspase; cationic nanoparticle; nanotoxicity; RNAi
Funding
- Portuguese Fundacao para a Ciencia e Tecnologia [SFRH/BD/15892/2005]
- Science Foundation Ireland [09/IN.1/B2604, SFI/SRC/B1155]
- strategic initiative award from the UCD College of Science
- Fundação para a Ciência e a Tecnologia [SFRH/BD/15892/2005] Funding Source: FCT
- Science Foundation Ireland (SFI) [09/IN.1/B2604] Funding Source: Science Foundation Ireland (SFI)
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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.
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