Lanthanide-based tools for the investigation of cellular environments

Abstract

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.

Single-Chain Lanthanide Luminescence Biosensors for Cell-Based Imaging and Screening of Protein-Protein Interactions

“…Recent years have seen efforts to engineer lanthanide complexes for cell-based, TGL biosensing and imaging applications including sensing of pH, metal ions, nucleic acids, enzymatic activities, and PPIs ( Aulsebrook et al., 2018 ; Mathieu et al., 2018 ; New et al., 2010 ; Rajendran et al., 2014 ; Zhang et al., 2018 ). A number of studies reported proof-of-concept LRET microscopic imaging of molecular interactions between Tb(III)- or Eu(III)-labeled and fluorophore-labeled species on cell surfaces including G-protein-coupled receptor (GPCR) ligand binding ( Delbianco et al., 2014 ), GPCR oligomerization ( Comps-Agrar et al., 2012 ; Faklaris et al., 2015 ), cadherin interactions ( Linden et al., 2015 ), and interactions between complementary morpholino probes in zebrafish embryos ( Cho et al., 2018 ).…”

Advances in anion binding and sensing using luminescent lanthanide complexes

“…The creation of Ln(III)based anion receptors is driven by the need for new sensing and imaging tools for biological, clinical and drug discovery research. [1][2][3] For example, an emissive Ln(III) receptor capable of binding bicarbonate (HCO 3 À ) selectively could be used to image spatial-temporal HCO 3 À dynamics in living cells using uorescence microscopy, 4 potentially aiding the diagnosis and treatment of diseases such as renal disease and glaucoma. 5 A Ln(III) receptor that binds adenosine diphosphate (ADP) selectively could allow real-time analysis of kinase enzyme activity by monitoring the production of ADP, 6 thereby providing a convenient luminescence assay for high throughput screening of potential kinase inhibitors for the treatment of cancer.…”

Triplexed CEA-NSE-PSA Immunoassay Using Time-Gated Terbium-to-Quantum Dot FRET

“…Coordination of the luminescent lanthanide ion inside supramolecular chelates or cryptates can enhance the absorption by more than 1000-fold via the antenna effect and efficiently protect the lanthanide ion from the environment to circumvent PL quenching and yield high PL quantum yields [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. Such bright and stable lanthanide complexes have been used in many different applications concerning highly sensitive, multiplexed, and background-free biological and chemical sensing and imaging [ 18 , 19 , 20 , 21 , 22 , 23 ].…”