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

Abstract

Cisplatin‐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 = 7.6 × 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 (FF) 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 (FD: 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.

Type‐I Photodynamic Therapy Induced by Pt‐Coordination of Type‐II Photosensitizers into Supramolecular Complexes

“…This demonstrated that NPs 1 containing supramolecular dimer (Cz−BTZ−Py) 2 Pt(OTf) 2 exhibited higher toxicity than NPs 2 . The superior phototoxicity of NPs 1 was attributed not only to the excellent photoinduced ROS generation efficiency of supramolecular dimer (Cz−BTZ−Py) 2 Pt(OTf) 2 , but also to the intrinsic antitumor activity of Pt (II) metal [28,43–45] which was verified by a slightly higher toxicity with increased concentrations in the dark group (Figure 5c). The MTT assay demonstrated that NPs 1 self‐assembled by supramolecular dimer (Cz−BTZ−Py) 2 Pt(OTf) 2 possessed remarkable antitumor efficiency due to the synergetic effect between PDT involving 1 O 2 and O 2 ⋅ − generation and chemotherapy.…”