Considerations for the Uptake Characteristic of Inorganic Nanoparticles into Mammalian Cells—Insights Gained by TEM Investigations

Abstract The internalization of nanoparticles into mammalian cells relies on a complex interplay of several parameters, which enable and dictate uptake and fate of nanoparticles in the cellular system. Due to the complexity of the involved processes, a careful experimental design has to be developed to elucidate peculiarities of the uptake processes of new nanoparticle systems into cells. Individual parameters can be hardly considered alone but have to be carefully evaluated, as striking alterations of the particle internalization and fate might be induced. In this review, essential parameters are summarized and illustrative examples are presented demonstrating the consequences of the different parameters. Special focus is placed in this context on studies, which utilize transmission electron microscopy (TEM) to elucidate the particles’ impact on the cells and to verify the nanoparticle uptake, localization as well as their effect on the cellular environment. Even though TEM is only one representative of a large number of very valuable investigation tools, the exceptional value, in particular, in view of the high resolution capabilities of TEM investigations is demonstrated by the chosen examples.