Add time:08/31/2019         Source:sciencedirect.com

As a first step in the process of developing folate based visual probes and contrast agents, we have designed and synthesised a series of first generation lanthanide(III) molecular probes. The molecular probe structure included a lanthanide(III) (Eu(III), Tb(III), Gd(III)) chelate which was linked (2 or 3) to either a folic acid or pteroic acid targeting motif. We have defined the emission properties of the molecular probes at different pHs, the emission lifetimes, and the number of metal bound water molecules. The cellular uptake of the molecular probes was investigated in HeLa cells and the amount of Eu(III) internalisation quantified by inductively coupled plasma mass spectrometry. Our results highlighted several key features of probe design: a shorter linker was more optimal for both Eu(III) ion emission intensity and cellular uptake; the folic acid targeting motif exhibited higher cellular uptake when compared to pteroic acid; the emission intensity of the folic acid based probes was pH insensitive, whereas the pteroic acid based probes were pH sensitive. These first generation folate molecular probes displayed promising chemical and physical properties, suggesting that optical and MRI probes can potentially be developed, to enable the imaging of folate receptors in cancer cells and tissues.

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