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Ulrica Englund Johansson, Erika Söderstjerna, Birgitta Klefbohm, Hodan Abdshill, Fredrik Johansson; Effects Of Silver- And Gold Nanoparticles On The Retina - Drug Delivery And Toxicity. Invest. Ophthalmol. Vis. Sci. 2012;53(14):300.
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The overall goal is to explore the potential use of nanoparticles (NPs) as carriers in drug delivery of therapeutical agents to the retina. Nanomaterials are increasingly used in diagnostics, imaging and targeted drug delivery. Au-NPs are currently employed in the clinic as e.g. anti-cancr agents and Ag-NPs are also commonly used in the clinic due to their antibacterial effects. Despite their widespread use, the documentation is limited on the direct effect of Ag-and Au-NPs on eukaryotic cells, including human cells and the eye/retina. Here we investigate the uptake and distribution of especially Ag- and Au-NPs as well as their eventual toxic effect.
The NPs are studied at a cellular-, tissue and organ level, using a human neural stem cell line, organotypic cultures of the mouse retina and last the mouse eye/retina as a model. Cell viability is assessed using MTT assay and well-known markers for apoptotic cells (e.g. PI- and TUNEL stainings). Cell proliferation- and cell cycle analysis are made using the human cell line, where also the effect on phenotypic differentiation is assessed using glial- and neuronal specific antibodies and immunostainings. In the models of the retina also the glial response is studied. Uptake and distribution of the NPs are analysed using TEM. AgNO3 is used as a positive control for the reported toxic effect of Ag ions. Ag- and Au-NPs of two different sizes are included, 20 and 80 nm, respectively. Furthermore, the NPs were administrated in two different concentrations 50 NPs/cell and 800 NPs/cell.
Our results clearly demonstrate that AgNO3 in a dose-dependent manner has a negative effect on cell viability using the human cell line and organotypic cultured retina. In addition, we have in repeated experiments noted a decrease in cell- proliferation and viability in the human cell line especially using the larger sized and higher concentration of Ag- and Au-NPs. Initial results also indicate that in a similar size- and concentration dependence also the cultured retina is affected by the NPs.
In summary, our initial results suggest that size and concentration of the NPs need to be carefully considered in medical applications and their eventual toxic effect to biological systems assessed.
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