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

Abstract

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 (ε = 9.8 × 10⁴ M⁻¹ cm⁻¹) with a shoulder at ∼624 nm and a broad emission at ∼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 µM) 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 µM) 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.