Luminescent platinum(ii) complexes with self-assembly and anti-cancer properties: hydrogel, pH dependent emission color and sustained-release properties under physiological conditionsElectronic supplementary information (ESI) available: Synthesis and characterization data, biological studies, supplementary figures/tables. X-ray crystallographic data of 1(ClO4). CCDC 1058788. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4sc03635b

• Main Authors: Tsai, Johnson Lui-Lui, Zou, Taotao, Liu, Jia, Chen, Tianfeng, Chan, Anna On-Yee, Yang, Chen, Lok, Chun-Nam, Che, Chi-Ming
• Format: Article
• Language: English
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c4sc03635b

Supramolecular interactions are of paramount importance in biology and chemistry, and can be used to develop new vehicles for drug delivery. Recently, there is a surge of interest on self-assembled functional supramolecular structures driven by intermolecular metal-metal interactions in cellular conditions. Herein we report a series of luminescent Pt( ii ) complexes [Pt(C^N^N pyr )(C&z.tbd;NR)] + [HC^N^N pyr = 2-phenyl-6-(1 H -pyrazol-3-yl)-pyridine)] containing pincer type ligands having pyrazole moieties. These Pt( ii ) complexes exert potent cytotoxicity to a panel of cancer cell lines including primary bladder cancer cells and display strong phosphorescence that is highly sensitive to the local environment. The self-assembly of these complexes is significantly affected by pH of the solution medium. Based on TEM, SEM, ESI-MS, absorption and emission spectroscopy, and fluorescence microscopy together with cell based assays, [Pt(C^N^N pyr )(C&z.tbd;NR)] + complexes were observed to self-assemble into orange phosphorescent polymeric aggregates driven by intermolecular Pt( ii )-Pt( ii ) and ligand-ligand interactions in a low-pH physiological medium. Importantly, the intracellular assembly and dis-assembly of [Pt(C^N^N pyr )(C&z.tbd;NR)] + are accompanied by change of emission color from orange to green. These [Pt(C^N^N pyr )(C&z.tbd;NR)] + complexes accumulated in the lysosomes of cancer cells, increased the lysosomal membrane permeability and induced cell death. One of these platinum( ii ) complexes formed hydrogels which displayed pH-responsive and sustained release properties, leading to low-pH-stimulated and time-dependent cytotoxicity towards cancer cells. These hydrogels can function as vehicles to deliver anti-cancer agent cargo, such as the bioactive natural products studied in this work. Luminescent platinum( ii ) complexes show anti-cancer and pH-dependent self-assembly and sustained-release properties under physiological conditions.