Nanomaterial cytotoxicity is composition, size, and cell type dependent

Syed K Sohaebuddin,David Baker,Paul T Thevenot,Liping Tang,John W Eaton

doi:10.1186/1743-8977-7-22

Abstract

BackgroundDespite intensive research efforts, reports of cellular responses to nanomaterials are often inconsistent and even contradictory. Additionally, relationships between the responding cell type and nanomaterial properties are not well understood. Using three model cell lines representing different physiological compartments and nanomaterials of different compositions and sizes, we have systematically investigated the influence of nanomaterial properties on the degrees and pathways of cytotoxicity. In this study, we selected nanomaterials of different compositions (TiO2 and SiO2 nanoparticles, and multi-wall carbon nanotubes [MWCNTs]) with differing size (MWCNTs of different diameters < 8 nm, 20-30 nm, > 50 nm; but same length 0.5-2 μm) to analyze the effects of composition and size on toxicity to 3T3 fibroblasts, RAW 264.7 macrophages, and telomerase-immortalized (hT) bronchiolar epithelial cells.ResultsFollowing characterization of nanomaterial properties in PBS and serum containing solutions, cells were exposed to nanomaterials of differing compositions and sizes, with cytotoxicity monitored through reduction in mitochondrial activity. In addition to cytotoxicity, the cellular response to nanomaterials was characterized by quantifying generation of reactive oxygen species, lysosomal membrane destabilization and mitochondrial permeability. The effect of these responses on cellular fate - apoptosis or necrosis - was then analyzed. Nanomaterial toxicity was variable based on exposed cell type and dependent on nanomaterial composition and size. In addition, nanomaterial exposure led to cell type dependent intracellular responses resulting in unique breakdown of cellular functions for each nanomaterial: cell combination.ConclusionsNanomaterials induce cell specific responses resulting in variable toxicity and subsequent cell fate based on the type of exposed cell. Our results indicate that the composition and size of nanomaterials as well as the target cell type are critical determinants of intracellular responses, degree of cytotoxicity and potential mechanisms of toxicity.

Highlights

Despite intensive research efforts, reports of cellular responses to nanomaterials are often inconsistent and even contradictory
Some reports indicated that exposure of cells to TiO2 leads to lipid peroxidation, DNA damage, caspase activation followed by micronuclei formation, chromatin condensation and eventual cell death via apoptosis [14,15,16,17]
Nanomaterial-mediated cell toxicity - Mitochondrial membrane potential and caspase-3/7 activation in nanoparticle exposed cells To search for alternative mechanisms of nanomaterialmediated cytotoxicity in human bronchiolar epithelial cells (hT) bronchiolar epithelial cells and RAW macrophages, we examined the changes of mitochondrial membrane potential (MMP) in all cell lines after particle exposure

Summary

Introduction

Reports of cellular responses to nanomaterials are often inconsistent and even contradictory. Other investigators have reported that TiO2 nanoparticle exposure instead causes plasma membrane damage and decrements in mitochondrial function [18,19,20]. There are even reports that TiO2 exposure does not lead to membrane damage, caspase activation or cell death [21,22]. One study concluded that lysosomal destabilization was the initiating factor [24] whereas two others concluded that loss of mitochondrial membrane integrity was the predominant cause of cell death [23,25]. It is possible that lysosomal destabilization and loss of mitochondrial membrane integrity may be related events [26] In contrast to these findings, other investigators reported that SiO2 exposure leads to plasma membrane damage [9,27] similar to observations with MWCNTs [28]. MWCNT were reported to cause a decrease in mitochondrial membrane potential [31,32] whereas another study reported that these nanotubes were non-toxic [33]

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