Cyclometalated iridium(iii) complexes as lysosome-targeted photodynamic anticancer and real-time tracking agents

Abstract

We report the rational design and photodynamic anticancer mechanism studies of iridium(iii) complexes with pH-responsive singlet oxygen (1O2) production and lysosome-specific imaging properties.

Evaluation of Perylene Bisimide‐Based RuII and IrIII Complexes as Photosensitizers for Photodynamic Therapy

“…Therefore, the production of singlet oxygen should be strongly favored by these compounds. Firstly, we confirmed the stability and photostability of both complexes up to 72 h in a CH 3 50 in the nanomolar range and PIs from > 7.8 to > 23, depending on the cell line. The investigation of the cellular uptake and localization of the complexes based on ICP-MS analysis indicated a nuclear accumulation for 1 and a mitochondrial localization for 2.…”

“…These compounds display good photostability, as well as interesting singlet oxygen generation upon irradiation at 420 nm (in particular 2). Their biological activity was evaluated on four cell lines and, although the cytotoxicity of 1 did not improve significantly upon light irradiation, 2, which localizes in mitochondria of HeLa cells as indicated by ICP-MS measurements, reached nanomolar IC 50 values on all the cell lines tested when activated with 420 nm light in low doses (9.27 J cm -2 ).…”

“…[46] Nevertheless, several Ir III compounds, most commonly bearing cyclometalated ligands, have recently been found to be promising PDT agents. [46][47][48][49][50][51][52] Figure 1. Structures of TLD-1433, a PS in clinical trial as a PDT PS, and complexes 1 and 2 with their respective ligands L1 and L2 studied in this paper.…”

Ester-Modified Cyclometalated Iridium(III) Complexes as Mitochondria-Targeting Anticancer Agents

“…By virtue of their intrinsic phosphorescence, the cellular uptake behaviours of Ir(III) complexes can be investigated semi-quantitatively by confocal microscopy. Moreover, subcellular localization analysis can provide further hints for the investigation of anticancer mechanisms17. Confocal microscopic images show that both 4a (5 μM) and 4b (5 μM) can penetrate into A549 cells rapidly in 30 min and mainly retain within cytoplasm (Supplementary Fig.…”

“…On the other hand, cyclometalated Ir(III) complexes are also considered to be potent anticancer candidates as they can target subcellular organelles, inhibit protein activities and act as photodynamic therapeutic agents11121314151617. Our group has endeavored to develop cyclometalated Ir(III) complexes as multifunctional theranostic agents integrating anticancer properties and imaging capabilities14151617.…”