Synthesis, photophysical and cellular characterisation of folate and methotrexate labelled luminescent lanthanide complexes.

In this work we have developed a series of highly emissive europium(III) and terbium(III) complexes tethered to either folic acid (FA) or methotrexate (MTX), with the aim of developing visual probes that enable the imaging of folate receptors in cancer cells. The synthesis, photophysical properties and cellular behaviour are reported for four new lanthanide Ln(III) complexes, where either FA or MTX are tethered to 1,4,7-tris(carbonylmethyl)-10-(4'-quinolineacetic acid, (7'-acetamido)-1',2'-dihydro-2'-oxo)-1,4,7,10-tetraazacyclododecane Ln(III) complex, and Ln(III)=Eu(III) or Tb(III); herein referred to as Eu-FA, Eu-MTX, Tb-FA or Tb-MTX. All four complexes were found to be sensitive to the presence of the folate receptor in a range of cell lines. The MTX conjugates showed different cellular specificity in an oral adenosquamous carcinoma cell line (CAL-27) compared with the analogous FA conjugates. This suggests that it is viable to explore differences in folate receptors using folate vs. anti-folate probes, with labels that have different emissive properties (e.g. Eu-FA vs. Tb-MTX). The MTX complexes were found to be the most cytotoxic, with Eu-MTX showing greater cytotoxicity than free MTX or the isostructural Tb-MTX. This suggested that there could be a synergistic effect on toxicity for the Eu(III) chelate and the MTX components of the complex.

Biomolecule detection in porous silicon based microcavities via europium luminescence enhancement.

In this paper, we demonstrate the detection of europium-complex-labeled streptavidin in a porous silicon microcavity (pSiMC) via luminescence enhancement. The pSiMC platform was modified for optimized luminescence enhancement which encompassed changing the pore size of the microcavity to ensure molecular infiltration and adjusting the optical quality of the microcavity. Characterization of the optimized surface was performed by infrared spectroscopy, interferometric reflectance spectroscopy and luminescence measurements. Luminescence enhancement of the bound Eu(iii) complex by a factor of 3 was observed on the optimized pSiMC as compared to that on a single pSi layer. The ability of a pSiMC to act as a luminescence enhancing sensor was confirmed using streptavidin as a model analyte on a biotin-modified pSiMC. The sensor was able to detect Eu(iii) complex labeled streptavidin with a concentration as low as 150 nM. Furthermore, streptavidin was selectively detected when spiked in human wound fluid. The concept of detecting Eu(iii) labeled bioconjugates on pSiMC may be incorporated into the design of highly sensitive and specific point-of-care biosensors.