Adhesion and uptake mechanisms of amorphous silica micro and nanoparticles in an in vitro model of human alveolar epithelial cells
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2012
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Abstract
With increasing application of nanoparticles in various fields including automotives, catalysis, cosmetics, electronics, food and textiles and higher likelihood of human exposure, it is important to understand how these particles interact with cells. Also in medicine, nanotechnology based strategies to enhance the transport of different agents into specific tissues, cells or cellular compartments, require an understanding of nanoparticle-cell interactions.
Even with numerous publications in this field, there are still significant gaps in knowledge from particle characterization to initial particle-cell interactions and downstream events. The goal of this project is to address these issues systematically. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) are used to explore the links between initial adhesion of a particle to a cell and particle uptake. Amorphous silica is the model particle in this study because of its extensive applications. As the respiratory tract is a unique target for particles, an in vitro model of human type II alveolar epithelial cells (A549) is used. Adhesion and uptake mechanisms of amorphous silica micro and nanoparticles are compared and the effect of agglomeration on the interaction mechanisms is elucidated. Primary human lung fibroblasts are used as control. Transcytosis of the nanoparticles through A549 cells is also studied.
The results show differences in the mechanisms involved in the adhesion and uptake of nanoparticle agglomerates and microparticles even when the size of the microparticle is in the range of the nanoparticle agglomerates size. Also, nanoparticle agglomerates appear to induce the same cellular responses as individual nanoparticles. A549 and primary human lung fibroblasts respond differently to nanoparticles. However, for microparticles, adhesion and uptake mechanisms are similar for both cell types. Transcytosis studies show that nanoparticles are able to cross A549 cells.
TEM tomography reveals details of particle uptake and provides some leads on the endosomal escape of particles.
The methods developed in this project open up a spectrum of investigations that otherwise would not be possible such as screening a large library of particles on different target cells. In addition to a fast turnover, this method allows "dissecting" the early steps of particle-cell interaction, including the biophysical reasons for adhesion and the events that trigger particle uptake.
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Bibliography: p. 143-152
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Tehranian, S. (2012). Adhesion and uptake mechanisms of amorphous silica micro and nanoparticles in an in vitro model of human alveolar epithelial cells (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/4678