RNAi-mediated inhibition of apoptosis fails to prevent cationic nanoparticle-induced cell death in cultured cells

Nanomedicine
Mariana G BexigaJeremy C Simpson

Abstract

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. 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. We have used a focused RNAi strategy in 1321N1 cells to identify key proteins involved in the cytotoxicity induced by amine-modified polystyrene nanoparticles. 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. 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 demons...Continue Reading

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Methods Mentioned

BETA
PCR
confocal microscopy
dynamic light scattering
electron
protein
electrophoresis
transfection
gene knockdown

Software Mentioned

GraphPad
Image J
Columbus Image Analysis
PASW Statistics
Prism

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BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis

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