Lipophilic neutral iridium(III) complexes for phosphorescence imaging of lipid droplets and potential photodynamic therapy

Abstract

Compared with the recently reported large number of fluorescent lipid droplet (LD) probes based on organic fluorophores, phosphorescent LD probes based on transition metal complexes are much less reported. In addition, LDs are rarely studied as targets for photodynamic therapy (PDT). In this work, two lipophilic neutral iridium(III) complexes, namely [Ir(bt)2(hpd)] (denoted as LDIr1) and [Ir(piq)2(hpd)] (denoted as LDIr2) (where Hbt = 2-phenylbenzothiazole, Hpiq = 1-penylisoquinoline, Hhpd = 3,5-heptanedione), have been synthesized and characterized. These complexes exhibit long-lived orange to red phosphorescence emission and large Stokes shifts (ca. 160 nm). They can specifically stain LDs in living A549 and HepG2 cells, showing excellent biocompatibility and favourable photostability. Complex LDIr1 has been successfully applied for monitoring of oleic acid-induced LDs accumulation in living A549 cells and in vivo imaging of larval zebrafish. Moreover, these two iridium(III) complexes can efficiently generate singlet oxygen upon visible light (425 nm) irradiation to kill cancer cells effectively by means of PDT. They display impressive high phototoxicity index (PI) values of 1087 and 263 for complexes LDIr1 and LDIr2, respectively. This study provides useful insights into rational design of new metal complex-based LD-targeted phosphorescent probes and PDT agents.