A Platinum(II) Boron‐dipyrromethene Complex for Cellular Imaging and Mitochondria‐targeted Photodynamic Therapy in Red Light

Abstract

AbstractCisplatin‐derived platinum(II) complexes [Pt(NH3)2(pacac)](NO3) (1, DPP‐Pt) and [Pt(NH3)2(Acac‐RB)](NO3) (2, Acacplatin‐RB), where Hpacac is 1,3‐diphenyl‐1,3‐propanedione and HAcac‐RB is a red‐light active distyryl‐BODIPY‐appended acetylacetone ligand, are prepared, characterized and their photodynamic therapy (PDT) activity studied (RB abbreviated for red‐light BODIPY). Complex 2 displayed an intense absorption band at λ=652 nm (ϵ=7.3×104 M−1 cm−1) and 601 nm (ϵ=3.1×104 M−1 cm−1) in 1 : 1 DMSO‐DPBS (Dulbecco's Phosphate Buffered Saline). Its emission profile includes a broad maximum at ~673 nm (λex=630 nm). The fluorescence quantum yield (ΦF) of HAcac‐RB and 2 are 0.19 and 0.07, respectively. Dichlorodihydrofluorescein diacetate and 1,3‐diphenylisobenzofuran assay of complex 2 indicated photogeneration of singlet oxygen (ΦΔ: 0.36) as reactive oxygen species (ROS). Light irradiation caused only minor extent of ligand release forming chemo‐active cisplatin analogue. The complex showed ~70–100 fold enhancement in cytotoxicity on light exposure in A549 lung cancer cells and MDA‐MB‐231 multidrug resistant breast cancer cells, giving half maximal inhibitory concentration (IC50) of 0.9–1.8 μM. Confocal imaging showed its mitochondrial localization and complex 2 exhibited anti‐metastasis properties. Immunostaining of β‐tubulin and Annexin V‐FITC/propidium iodide staining displayed complex 2 induced photo‐selective microtubule rupture and cellular apoptosis, respectively.