Fluorescent Analogues of Potential Cancer Theranostic Agents

Abstract

In this project, a number of novel fluorescent lanthanoid complexes were synthesised and fully characterised. These complexes utilised both europium(III) and terbium(III) centres, coordinated by a DO3A-based ligand structure. A linker domain, typically consisting of a fluorescent sensitising antenna group (i.e. a xylyl, 2o-amide-xylyl, or naphthyl group), was used to connect the central ligand structure to a targeting moiety, which consisted of a DLC known as triphenylphosphonium (TPP).

Fluorescence excitation and emission spectroscopic properties as well q values were determined, which are relevant in maximising fluorescent yield. A selection of these metal complexes (i.e. 13, 14, 16, 17) were visualised inside intact human cancer and normal cells using fluorescent microscopy. Enhanced co-localisation was observed for both the metal complexes and the MitoTracker Deep Red (MTDR) probe within human cancer (glioblastoma T98G) cells relative to normal (foetal glial SVG-p12) cells. Such studies were complemented by ICP-MS cell uptake studies.

These fluorescent studies serve as a strong precedent for a relatively time-efficient, cheap and effective means of analysing cellular localisation of this class of metal complexes, which can hopefully be incorporated into future studies involving analogues of such complexes, and can potentially replace other more time-intensive and costly methods such as synchrotron XRF studies.