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Silica nanoconstruct cellular toleration threshold in vitro.

ABSTRACT: The influence of geometry of silica nanomaterials on cellular uptake and toxicity on epithelial and phagocytic cells was studied. Three types of amine-terminated silica nanomaterials were prepared and characterized via the modified Stober method, namely spheres (178±27 nm), worms (232±22 nm×1348±314 nm) and cylinders (214±29 nm×428±66 nm). The findings of the study suggest that in this size range and for the cell types studied, geometry does not play a dominant role in the modes of toxicity and uptake of these particles. Rather, a concentration threshold and cell type dependent toxicity of all particle types was observed. This correlated with confocal microscopy observations, as all nanomaterials were observed to be taken up in both cell types, with a greater extent in phagocytic cells. It must be noted that there appears to be a concentration threshold at ~100 ?g/mL, below which there is limited to no impact of the nanoparticles on membrane integrity, mitochondrial function, phagocytosis or cell death. Analysis of cell morphology by transmission electron microscopy, colocalization experiments with intracellular markers and Western Blot results provide evidence of potential involvement of lysosomal escape, autophagic like activity, compartmental fusion and recycling in response to intracellular nanoparticle accumulation. These processes could be involved in cellular coping or defense mechanisms. The manipulation of physicochemical properties to enhance or reduce toxicity paves the way for the safe design of silica-based nanoparticles for use in nanomedicine.

SUBMITTER: Herd HL

PROVIDER: S-EPMC3197243 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Silica nanoconstruct cellular toleration threshold in vitro.

Herd Heather L HL Malugin Alexander A Ghandehari Hamidreza H

Journal of controlled release : official journal of the Controlled Release Society 20110220 1

The influence of geometry of silica nanomaterials on cellular uptake and toxicity on epithelial and phagocytic cells was studied. Three types of amine-terminated silica nanomaterials were prepared and characterized via the modified Stober method, namely spheres (178±27 nm), worms (232±22 nm×1348±314 nm) and cylinders (214±29 nm×428±66 nm). The findings of the study suggest that in this size range and for the cell types studied, geometry does not play a dominant role in the modes of toxicity and ...[more]

PMID: 21342660

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Project description:BackgroundWith increasing knowledge about the potential mechanisms underlying cellular functions, it is becoming feasible to predict the response of biological systems to genetic and environmental perturbations. Due to the lack of homogeneity in living tissues it is difficult to estimate the physiological effect of chemicals, including potential toxicity. Here we investigate a biologically motivated model for estimating tissue level responses by aggregating the behavior of a cell population. We assume that the molecular state of individual cells is independently governed by discrete non-deterministic signaling mechanisms. This results in noisy but highly reproducible aggregate level responses that are consistent with experimental data.ResultsWe developed an asynchronous threshold Boolean network simulation algorithm to model signal transduction in a single cell, and then used an ensemble of these models to estimate the aggregate response across a cell population. Using published data, we derived a putative crosstalk network involving growth factors and cytokines - i.e., Epidermal Growth Factor, Insulin, Insulin like Growth Factor Type 1, and Tumor Necrosis Factor α - to describe early signaling events in cell proliferation signal transduction. Reproducibility of the modeling technique across ensembles of Boolean networks representing cell populations is investigated. Furthermore, we compare our simulation results to experimental observations of hepatocytes reported in the literature.ConclusionA systematic analysis of the results following differential stimulation of this model by growth factors and cytokines suggests that: (a) using Boolean network ensembles with asynchronous updating provides biologically plausible noisy individual cellular responses with reproducible mean behavior for large cell populations, and (b) with sufficient data our model can estimate the response to different concentrations of extracellular ligands. Our results suggest that this approach is both quantitative, allowing statistical verification and calibration, and extensible, allowing modification and revision as guided by experimental evidence. The simulation methodology is part of the US EPA Virtual Liver, which is investigating the effects of everyday contaminants on living tissues. Future models will incorporate additional crosstalk surrounding proliferation as well as the putative effects of xenobiotics on these signaling cascades within hepatocytes.

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Silica nanoconstruct cellular toleration threshold in vitro.

Publications

Silica nanoconstruct cellular toleration threshold in vitro.

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