Targeting cancer cell metabolism with mitochondria-immobilized phosphorescent cyclometalated iridium(iii) complexes

Abstract

We report a rational design and mechanism studies of mitochondria-immobilized iridium(iii) complexes that can kill cancer cells by targeting mitochondrial metabolism.

Anticancer IrIII–Aspirin Conjugates for Enhanced Metabolic Immuno‐Modulation and Mitochondrial Lifetime Imaging

“…Ir1 was prepared according to al iterature method. [35] Ir2 and Ir3 were similarly synthesized by reacting the Ir III precursorsw ith the corresponding ligands in CH 2 Cl 2 /CH 3 OH (1:1, v/v). The ligands (L2 and L3)a nd the complexes (Ir2 and Ir3)w ere characterized by ESI-MS ( The photophysical properties of Ir2 and Ir3 in CH 3 CN, CH 2 Cl 2 ,a nd phosphate-buffered saline (PBS)w ere tested (Figures S13 and S14;T able S1).…”

“…Synthesis of Ir1-Ir3:T he dimeric iridium(III) precursor [Ir(ppy) 2 (m-Cl)] 2 was prepared according to al iterature method. Complex Ir1 was synthesized according to al iterature method, [35] and complexes Ir2 and Ir3 were synthesized analogously.Amixture of [Ir(ppy) 2 (m-Cl)] 2 (0.2 mmol) and L2 (0.4 mmol) or L3 (0.4 mmol) in CH 2 Cl 2 /CH 3 OH (1:1, v/v) was heated to reflux under the protection of an itrogen atmosphere in the dark for 6h.T he solution was cooled to room temperature and concentrated to dryness under reduced pressure. The oily residue was taken up in CH 2 Cl 2 and purified by column chromatography on silica gel, eluting with CH 2 Cl 2 / CH 3 OH.…”

“…Analysis of mitochondrial bioenergetics:T he experiment was carried out as described in the literature. [35] PC3 cells were seeded at 2 10 4 per well. The optimal concentrations of the compounds were as follows:o ligomycin (1 mm), carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) (0.8 mm), and am ixture of antimycin A( 0.5 mm)and rotenone (0.5 mm).…”

Photodamaging of Mitochondrial DNA to Overcome Cisplatin Resistance by a RuII–PtII Bimetallic Complex

“…The experiment was carried out as described in literature. [43] Colocalization assay of DCF and MTDR A549 cells were seeded in 35 mm dishes and treated with Ru (1 mm)o rRuPt (1 mm)f or 12 h. Cells were further incubated with H 2 DCFDA (10 mm) for 20 min at 37 8Ci nt he dark and then irradiated with a4 50 nm LED light array (17 mW cm À2 ,5Jcm À2 ). Then cells were co-incubated with MTDR (150 nm)a t3 78Cf or another 0.5 h and washed three times with PBS and visualized by ac onfocal microscope.…”

A Cyclometalated IrIII Complex as a Lysosome‐Targeted Photodynamic Therapeutic Agent for Integrated Imaging and Therapy in Cancer Cells

“…[11] The relativelyl ow-energy bands between about 440 and 510 nm, with extinction coefficients (e) of 6110-21 214 m À1 cm À1 ,c an be attributedt om ixed singlet and triplet metal-to-ligand charge-transfer ( 1 MLCT and 3 MLCT) and ligand-to-ligand charge-transfer(LLCT)t ransitions. [11] Ir-Bp-Ly exhibits red phosphorescence in acetonitrile (615 nm) ( Figure S4) and PBS (620 nm) upon excitation at 465 nm (Figures 1a nd S4). The long emission lifetimeo f 1.47 msi na cetonitrile can be ascribed to triplet emission from the complex.…”