Synthesis and tumour cell uptake studies of gadolinium(III)\u2013phosphonium complexes

Andrew J Hall,Leila R Hill,Amy G Robertson,Louis M Rendina

doi:10.1038/s41598-020-79893-9

Andrew J Hall, Leila R Hill + Show 2 more

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https://doi.org/10.1038/s41598-020-79893-9

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Journal: Scientific Reports	Publication Date: Jan 12, 2021
Citations: 5	License type: open-access

Affiliation: University of Sydney

Abstract

The synthesis of a new series of Gd(III)-arylphosphonium complexes is described and the solution stability of selected compounds is reported. Their lipophilicity and uptake in human glial (SVG p12) and human glioblastoma multiforme (T98G) cell lines are presented. The in vitro cytotoxicity of all complexes was determined to be low at therapeutically-relevant concentrations. Selected Gd(III) complexes are potential candidates for further investigation as theranostic agents.

Highlights

The synthesis of a new series of Gd(III)-arylphosphonium complexes is described and the solution stability of selected compounds is reported
Novel Gd(III) complexes (1–5) were synthesised utilising phosphonium mitochondrial-targeting vectors based upon related prototype Gd(III) complexes that we have reported previously[8,9]
Stability assays comparing the DOTA-based complex 1 to the previously-reported, archetypal DO3A-phosphonium complex 11 at mildly acidic pH conditions demonstrated a significant increase in the stability of 1, and these findings are consistent with those previously reported for Gd(III)-DOTA complexes by Caravan et al.[26]

Summary

Introduction

The synthesis of a new series of Gd(III)-arylphosphonium complexes is described and the solution stability of selected compounds is reported Their lipophilicity and uptake in human glial (SVG p12) and human glioblastoma multiforme (T98G) cell lines are presented. When coupled with relevant lanthanoid chelators these phosphonium DLCs are able to selectively shuttle medically-relevant metal ions into the mitochondria of these cancer cells independent of endogenous transporters[4,5,6] Initial investigations of these ligands have demonstrated their promise as candidates for the development of Gd(III)-based t heranostics[7,8,9]. We report the synthesis and a limited stability and SAR study of a novel series of Gd(III)-DOTA-phosphonium complexes The uptake of these complexes in human glial (SVG p12) and human glioblastoma multiforme (T98G) cell lines is presented

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Conclusion