摘要：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.Four highly emissive lanthanide complexes which combine a carbostyril antenna coupled to a cyclen chelate tethered to either folic acid or methotrexate were synthesised and characterised. Fluorescence microscopy and cytotoxicity were investigated to explore the relationship between lanthanide ion and targeting motif.Display Omitted• Four lanthanide ion complexes tethered to folic acid or methotrexate were prepared. • Synthesis and photophysical behaviour were explored to evaluate pH sensitivity. • The targeting of the folate receptors in non-malignant and malignant cells was explored.