Lanthanide-based tools for the investigation of cellular environments.

Biological probes constructed from lanthanides can provide a variety of readout signals, such as the luminescence of Eu(iii), Tb(iii), Yb(iii), Sm(iii) and Dy(iii), and the proton relaxation enhancement of Gd(iii) and Eu(ii). For numerous applications the intracellular delivery of the lanthanide probe is essential. Here, we review the methods for the intracellular delivery of non-targeted complexes (i.e. where the overall complex structure enhances cellular uptake), as well as complexes attached to a targeting unit (i.e. to a peptide or a small molecule) that facilitates delivery. The cellular applications of lanthanide-based supramolecules (dendrimers, metal organic frameworks) are covered briefly. Throughout, we emphasize the techniques that can confirm the intracellular localization of the lanthanides and those that enable the determination of the fate of the probes once inside the cell. Finally, we highlight methods that have not yet been applied in the context of lanthanide-based probes, but have been successful in the intracellular delivery of other metal-based probes.