Heterogeneity in a cell population is a universal phenomenon in all biological systems including whole tissues, and cell cultures.[1] Intra-tumour heterogeneity has been widely reported for decades from morphological perspectives, whereas phenotypic and genotypic heterogeneity has also been detected.[2] DNA platination is widely assumed as the central mode of action for most platinum anti-cancer drugs. This generalisation on the mode of action for conventional chemotherapy may actually impede effective drug development. Clinical approval for most novel anti-cancer drugs has been denied due to uncertainty in optimal usage, and the modes of action unclear.[3] For a better understanding of variations, from cell to cell, in response to metal-based drugs, single cell analysis is the key. Single cell experiments should provide critical information about the pathway and disease state, which will guide personalised medicine and therapeutic strategies. Electrochemistry is the foremost approach for studying the uptake of metal-based drugs in single cells. This strategy involves positioning a micro or nanoelectrodes inside or near the surface of a single cell for the electrochemical monitoring of individual cellular events.[4]

In this work, the aim is to exploit single cell electrochemical analysis, to study the uptake of silver-based bioinorganic drugs and to elucidate the mode of action. Single cell electrochemistry experiments were carried out using the platinum and platinum-black nanoelectrodes on human lung carcinoma (A549) cell lines. Speciation studies of the silver-phenanthroline bioinorganic drugs was examined using stripping voltammetry for metal detection, and the redox behaviour analysis by cyclic voltammetry for in vitro and single cell analysis.

[1] Andrew G. Ewing. et al., Anal. Chem. 2019, 91, 1, 588-621

[2] Glenn Deng. et al., Front Cell Dev Biol. 2016, 4: 116.

[3] Walter Berger. et al., ESMO Open. 2017, 2(3): e000239.

[4] Dechen Jiang. et al., ACS Sens. 2018, 3 (2), 242–250