Efficient cytosolic delivery of luminescent lanthanide bioprobes in live cells for two-photon microscopy.

Lanthanide(iii) (Ln) complexes have desirable photophysical properties for optical bioimaging. However, despite their advantages over organic dyes, their use for microscopy imaging is limited by the high-energy UV excitation they require and their poor ability to cross the cell membrane and reach the cytosol. Here we describe a novel family of lanthanide-based luminescent probes, termed dTAT[Ln·L], based on (i) a DOTA-like chelator with a picolinate moiety, (ii) a two-photon absorbing antenna to shift the excitation to the near infrared and (ii) a dimeric TAT cell-penetrating peptide for cytosolic delivery.

Luminescent Peptide/Lanthanide(III) Complex Conjugates with Push-Pull Antennas: Application to One- and Two-Photon Microscopy Imaging.

Lanthanide(III) (Ln) complexes feature desirable luminescence properties for cell microscopy imaging, but cytosolic delivery of Ln complexes and their use for 2P imaging of live cells are challenging. In this article, we describe the synthesis and spectroscopic characterizations of a series of Ln complexes based on two ligands, and , featuring extended picolinate push-pull antennas for longer wavelength absorption and 2P absorption properties as well as a free carboxylate function for conjugation to peptides. Several cell penetrating peptide/Ln complex conjugates were then prepared with the most interesting luminescent complexes, Tb() and Eu(), and with two cell penetrating peptides (CPPs), ZF5.