Monofunctional Platin-BODIPY Bullet for Mitochondria-Targeted Chemo-PDT Activity

Monofunctional Pt(II) complexes [Pt(GL)Cl]Cl (GL-Pt-Cl) and [Pt(RL)Cl]Cl (RL-Pt-Cl), where GL and RL are green and red-light active PEGylated distyryl BODIPY-terpyridine moieties, were synthesized and their photo- and chemotherapeutic activity studied. BODIPY-terpyridine ligand was structurally characterized. RL-Pt-Cl showed an intense absorption peak at 658 nm (epsilon = 9.8 x 104 M-1 cm-1) with a shoulder at similar to 624 nm and a broad emission at similar to 672 nm in 10% DMSO/DPBS (Dulbecco's Phosphate Buffered Saline). It was produced 1O2 as evidenced from mechanistic studies. It displayed photocytotoxicity in red light (IC50: 0.7 mu M) in MDA-MB-231 cells. The 2 ',7 '-dichlorofluorescein diacetate assay indicated intracellular generation of reactive oxygen species. It showed chemotherapeutic activity (IC50: 13.7 mu M) in A549 cells on 24 h incubation. Pt-DNA adduct formation was proposed from the 9-ethylguanine binding experiment. Imaging of RL-Pt-Cl treated A549 cancer cells displayed its mitochondrial localization. JC-1 assay indicated loss of mitochondrial membrane potential in red light. The annexin V-FITC/propidium iodide assay suggested cellular apoptosis.