Cellular uptake and intracellular fate of engineered nanoparticles: a review on the application of imaging techniques.

The use of imaging tools to probe nanoparticle-cell interactions will be crucial to elucidating the mechanisms of nanoparticle-induced toxicity. Of particular interest are mechanisms associated with cell penetration, translocation and subsequent accumulation inside the cell, or in cellular compartments. The objective of the present paper is to review imaging techniques that have been previously used in order to assess such interactions, and new techniques with the potential to be useful in this area. In order to identify the most suitable techniques, they were evaluated and matched against a list of evaluation criteria. We conclude that limitations exist with all of the techniques and the ultimate choice will thus depend on the needs of end users, and their particular application. The state-of-the-art techniques appear to have the least limitations, despite the fact that they are not so well established and still far from being routine. For example, super-resolution microscopy techniques appear to have many advantages for understanding the details of the interactions between nanoparticles and cells. Future research should concentrate on further developing or improving such novel techniques, to include the development of standardized methods and appropriate reference materials.