< Back to previous page
Project
Physico-chemical determinants of the toxicity of silica nanoparticles
Nanomaterials are already impacting on virtually all sectors of industrial and domestic products (cosmetics, clothing, personal care, sporting goods, sunscreens, filtration, electronics and computers, food and beverage), and their production and marketing will increase in the coming years.
Silica nanoparticles (SiO2-NPs) are produced on an industrialscale and are an addition to a growing number of commercial products. SiO2-NPs also have great potential for a variety of diagnostic and therapeutic applications in medicine. Contrary to the well-studied crystallinemicron-sized silica, relatively little information exists on the toxicity of its amorphous and nano-size forms. Because nanoparticles possess novel properties, kinetics and unusual bioactivity, their potential biological effects may differ greatly from those of micron-size bulk materials.
The objectives of this project is to determine:
(1) which physico-chemical characteristics of nanoparticles direct the toxicity;
(2) which mechanisms are involved in the toxicity of silicananoparticles.
The strategy of the presented doctoral project was to conduct toxicity studies with a very carefully characterized model material silicon dioxide (silica) nanoparticles (SiO2-NPs). The general (cyto)toxicity of these particles was assessed and two specific mechanisms were Investigated; oxidative stress and endothelial dysfunction.
The effect that monodisperse amorphous spherical silica particles of different sizes have on the viability of endothelial cells (EA.hy926 cell line) was investigated. The results indicate that exposure to silicananoparticles causes cytotoxic damage (lactate dehydrogenase (LDH) release) and a decrease in cell survival (tetrazolium reduction, MTT assay)in the EA.hy926 cell line in a dose- and size-related manner. Concentrations leading to a 50% reduction in cell viability (TC50) for the rangedfrom 33 µg/cm² for the smallest particles (14 nm diameter) to 1087 µg/cm² for 335 nm diameter particles. The smaller particles also appear to affect the exposed cells faster, by necrosis, compared to the bigger particles. We showed that the surface area of monodisperse amorphous silica nanoparticles is an important parameter in determining the toxicity.
A similar study has been undertaken using nanosized zeolite particles (crystalline silica particles). The synthesis of nanozeolites Y and A resulted in particle sizes of 25-100 nm and an adequate colloidal stability for in vitro </>cytotoxicity experiments. Thecytotoxic response of macrophages, epithelial and endothelial cells to these nanocrystals was also assessed by the MTT assay and the LDH leakage assay. After 24h of exposure, no significant cytotoxic activity was detected for zeolite doses up to 500 μg/ml.
Addition of fetalcalf serum to the cell culture medium during exposure did not significantly change this low response. The nanozeolites are of low toxicity compared with monodisperse amorphous silica nanoparticles of similar size (60 nm). These results may contribute to the application of nanozeolites for purposes such as medical imaging, sensing materials, low-k </>films and molecular separation processes.
The association of oxidative stress with SiO2-NPs induced cytotoxicity in human endothelial cells was studied with pure monodisperse amorphous silica nanoparticles oftwo sizes (16 and 60 nm; S16 and S60) and iron-doped nanosilica (19 nm;SFe). We found significant modifications in GSSG/total glutathione ratio and MDA and HAE concentrations only in cells treated with SFe nanoparticles. Significantly higher HO-1 mRNA expression was found in endothelial cells after 6h treatment with S16 or SFe nanoparticles; no such up-regulation was seen with S60 particles. Our study demonstrates that cytotoxicity occurs in endothelial cells exposed to pure SiO2-NPs in the absence of oxidative stress.
There is evidence suggesting that nanoparticles can induce endothelial dysfunction, which may lead to vascular diseases. The present study was undertaken to examine the effect of amorphous (monodisperse) SiO2-NPs of different sizes (28, 59 and 174 nm) on endothelial (EA.hy 926 cell line or primary hPAEC)
cell function, in theabsence or presence of a previously established in vitro </>human airway model consisting of triple cell co-cultures.
</>At non-toxic concentrations, a significant increase (up to 2-fold) in U937 cell adhesion was observed. Exposure to all three SiO2-NPs induced expression of ICAM-1 but no VCAM-1 in the EA.hy 926 and ICAM-1 and VCAM-1 in hPAEC cultures. Experiments performed with fluorescently labeled amorphous monodisperse SiO2-NPs (24 nm) showed the uptake of the nanoparticles into the cytoplasm of both EC tested. We concluded that exposure of human endothelial cells to amorphous silica nanoparticles enhancesadhesive properties of the studied cells.
</></></>
Silica nanoparticles (SiO2-NPs) are produced on an industrialscale and are an addition to a growing number of commercial products. SiO2-NPs also have great potential for a variety of diagnostic and therapeutic applications in medicine. Contrary to the well-studied crystallinemicron-sized silica, relatively little information exists on the toxicity of its amorphous and nano-size forms. Because nanoparticles possess novel properties, kinetics and unusual bioactivity, their potential biological effects may differ greatly from those of micron-size bulk materials.
The objectives of this project is to determine:
(1) which physico-chemical characteristics of nanoparticles direct the toxicity;
(2) which mechanisms are involved in the toxicity of silicananoparticles.
The strategy of the presented doctoral project was to conduct toxicity studies with a very carefully characterized model material silicon dioxide (silica) nanoparticles (SiO2-NPs). The general (cyto)toxicity of these particles was assessed and two specific mechanisms were Investigated; oxidative stress and endothelial dysfunction.
The effect that monodisperse amorphous spherical silica particles of different sizes have on the viability of endothelial cells (EA.hy926 cell line) was investigated. The results indicate that exposure to silicananoparticles causes cytotoxic damage (lactate dehydrogenase (LDH) release) and a decrease in cell survival (tetrazolium reduction, MTT assay)in the EA.hy926 cell line in a dose- and size-related manner. Concentrations leading to a 50% reduction in cell viability (TC50) for the rangedfrom 33 µg/cm² for the smallest particles (14 nm diameter) to 1087 µg/cm² for 335 nm diameter particles. The smaller particles also appear to affect the exposed cells faster, by necrosis, compared to the bigger particles. We showed that the surface area of monodisperse amorphous silica nanoparticles is an important parameter in determining the toxicity.
A similar study has been undertaken using nanosized zeolite particles (crystalline silica particles). The synthesis of nanozeolites Y and A resulted in particle sizes of 25-100 nm and an adequate colloidal stability for in vitro </>cytotoxicity experiments. Thecytotoxic response of macrophages, epithelial and endothelial cells to these nanocrystals was also assessed by the MTT assay and the LDH leakage assay. After 24h of exposure, no significant cytotoxic activity was detected for zeolite doses up to 500 μg/ml.
Addition of fetalcalf serum to the cell culture medium during exposure did not significantly change this low response. The nanozeolites are of low toxicity compared with monodisperse amorphous silica nanoparticles of similar size (60 nm). These results may contribute to the application of nanozeolites for purposes such as medical imaging, sensing materials, low-k </>films and molecular separation processes.
The association of oxidative stress with SiO2-NPs induced cytotoxicity in human endothelial cells was studied with pure monodisperse amorphous silica nanoparticles oftwo sizes (16 and 60 nm; S16 and S60) and iron-doped nanosilica (19 nm;SFe). We found significant modifications in GSSG/total glutathione ratio and MDA and HAE concentrations only in cells treated with SFe nanoparticles. Significantly higher HO-1 mRNA expression was found in endothelial cells after 6h treatment with S16 or SFe nanoparticles; no such up-regulation was seen with S60 particles. Our study demonstrates that cytotoxicity occurs in endothelial cells exposed to pure SiO2-NPs in the absence of oxidative stress.
There is evidence suggesting that nanoparticles can induce endothelial dysfunction, which may lead to vascular diseases. The present study was undertaken to examine the effect of amorphous (monodisperse) SiO2-NPs of different sizes (28, 59 and 174 nm) on endothelial (EA.hy 926 cell line or primary hPAEC)
cell function, in theabsence or presence of a previously established in vitro </>human airway model consisting of triple cell co-cultures.
</>At non-toxic concentrations, a significant increase (up to 2-fold) in U937 cell adhesion was observed. Exposure to all three SiO2-NPs induced expression of ICAM-1 but no VCAM-1 in the EA.hy 926 and ICAM-1 and VCAM-1 in hPAEC cultures. Experiments performed with fluorescently labeled amorphous monodisperse SiO2-NPs (24 nm) showed the uptake of the nanoparticles into the cytoplasm of both EC tested. We concluded that exposure of human endothelial cells to amorphous silica nanoparticles enhancesadhesive properties of the studied cells.
</></></>
Date:1 Jan 2008 → 30 May 2011
Keywords:Nanoparticles
Disciplines:Respiratory medicine
Project type:PhD project