A Platinum(II) Boron‐dipyrromethene Complex for Cellular Imaging and Mitochondria‐targeted Photodynamic Therapy in Red Light
Aarti Upadhyay, Amrita Nepalia, Arpan Bera, Deepak Kumar Saini, Akhil R. Chakravarty
Abstract
Abstract Cisplatin‐derived platinum(II) complexes [Pt(NH 3 ) 2 (pacac)](NO 3 ) ( 1 , DPP‐Pt ) and [Pt(NH 3 ) 2 ( Acac‐RB )](NO 3 ) ( 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=7.3×10 4 M −1 cm −1 ) and 601 nm (ϵ=3.1×10 4 M −1 cm −1 ) in 1 : 1 DMSO‐DPBS (Dulbecco's Phosphate Buffered Saline). Its emission profile includes a broad maximum at ~673 nm (λ ex =630 nm). The fluorescence quantum yield (Φ F ) 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 (Φ Δ : 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 (IC 50 ) 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.