Evaluating the anticancer properties and real-time electrochemical extracellular bio-speciation of bis (1,10-phenanthroline) silver (I) acetate monohydrate in the presence of A549 lung cancer cells

Abstract

According to the American Cancer Society report (2019-2021), the majority (63%) of stage III non-small cell lung cancer (NSCLC) patients are prescribed with chemo and/or radiation therapies, with 5-year relative survival rates of just 19%. Thus, directed drug development, toward personalised cancer treatment, is widely recognised as a necessary strategy in drug discovery research. However, broad generalisations on the modes of action of bioinorganic compounds are not conducive to tailored drug design, hence, fundamental mechanistic research is essential in realising personalised healthcare. In this work, anticancer properties of bis (1,10-phenanthroline) silver (I) acetate monohydrate (Ag-Phen), toward A549 lung cancer cells are presented. Biological assays were carried out to evaluate the effect of Ag-Phen on cell viability, reactive oxygen species generation and mitochondrial membrane potentials. In tandem with the biological assays, electrochemistry was employed to determine the real-time concentrations of intact Ag-Phen and dissociated Ag⁺ in the extracellular medium using platinum microelectrodes, as a function of cellular exposure time. Observations from the assays conducted include, Ag-Phen induced cytotoxicity (IC₅₀ 4.5 μM at 72 h) and 2-fold ROS generation, and a 50% decrease in mitochondrial membrane potentials with respect to equivalent concentrations of Ag⁺ and 1,10-phenanthroline. Bio-speciation studies, conducted electrochemically at platinum microelectrodes, revealed almost 50% of the Ag-Phen had dissociated after 2 h. Significant reductions in concentrations of dissociated Ag⁺ (from 67.7 μM to 6.7 μM), and the Ag-Phen complex (from 50.2 μM to 11.7 μM) between 4 and 24 h from the extracellular medium, indicate cellular uptake of both. This novel method facilitates the real-time identification and quantification of electroactive species, both the intact Ag-Phen and Ag⁺, in the presence of A549 cells.

Keywords: Electrochemical sensing; Extracellular electrochemical detection; Microelectrode; Real-time detection; Silver-phenanthroline complex; Speciation.